CiteULike: apeyrache's library [279 articles]

Models and properties of power-law adaptation in neural systems.

PJ Drew — 2006-11-19T20:42:12-00:00

J Neurophysiol, Vol. 96, No. 2. (August 2006), pp. 826-833.

Many biological systems exhibit complex temporal behavior that cannot be adequately characterized by a single time constant. This dynamics, observed from single channels up to the level of human psychophysics, is often better described by power-law rather than exponential dependences on time. We develop and study the properties of neural models with scale-invariant, power-law adaptation and contrast them with the more commonly studied exponential case. Responses of an adapting firing-rate model to constant, pulsed, and oscillating inputs in both the power-law and exponential cases are considered. We construct a spiking model with power-law adaptation based on a nested cascade of processes and show that it can be "programmed" to produce a wide range of time delays. Finally, within a network model, we use power-law adaptation to reproduce long-term features of the tilt aftereffect.

Attractor neural network models of spatial maps in hippocampus.

M Tsodyks — 2008-07-23T14:52:36-00:00

Hippocampus, Vol. 9, No. 4. (1999), pp. 481-489.

Hippocampal pyramidal neurons in rats are selectively activated at specific locations in an environment (O'Keefe and Dostrovsky, Brain Res 1971;34:171-175). Different cells are active in different places, therefore providing a faithful representation of the environment in which every spatial location is mapped to a particular population state of activity of place cells (Wilson and McNaughton, Science 1993;261:1055-1058; Zhang et al., J Neurosci 1998;79:1017-1044). We describe a theory of the hippocampus, according to which the map results from the cooperative dynamics of network, in which the strength of synaptic interaction between the neurons depends on the distance between their place fields. This synaptic structure guarantees that the network possesses a quasi-continuous set of stable states (attractors) that are localized in the space of neuronal variables reflecting their synaptic interactions, rather than their physical location in the hippocampus. As a consequence of the stable states, the network can exhibit place selective activity even without relying on input from external sensory cues.

Paradoxical effects of external modulation of inhibitory interneurons.

MV Tsodyks — 2008-07-23T14:51:56-00:00

The Journal of neuroscience : the official journal of the Society for Neuroscience, Vol. 17, No. 11. (1 June 1997), pp. 4382-4388.

The neocortex, hippocampus, and several other brain regions contain populations of excitatory principal cells with recurrent connections and strong interactions with local inhibitory interneurons. To improve our understanding of the interactions among these cell types, we modeled the dynamic behavior of this type of network, including external inputs. A surprising finding was that increasing the direct external inhibitory input to the inhibitory interneurons, without directly affecting any other part of the network, can, in some circumstances, cause the interneurons to increase their firing rates. The main prerequisite for this paradoxical response to external input is that the recurrent connections among the excitatory cells are strong enough to make the excitatory network unstable when feedback inhibition is removed. Because this requirement is met in the neocortex and several regions of the hippocampus, these observations have important implications for understanding the responses of interneurons to a variety of pharmacological and electrical manipulations. The analysis can be extended to a scenario with periodically varying external input, where it predicts a systematic relationship between the phase shift and depth of modulation for each interneuron. This prediction was tested by recording from interneurons in the CA1 region of the rat hippocampus in vivo, and the results broadly confirmed the model. These findings have further implications for the function of inhibitory and neuromodulatory circuits, which can be tested experimentally.

Slow oscillations in neural networks with facilitating synapses.

Ofer Melamed — 2008-05-18T15:13:11-00:00

Journal of computational neuroscience (16 May 2008)

The synchronous oscillatory activity characterizing many neurons in a network is often considered to be a mechanism for representing, binding, conveying, and organizing information. A number of models have been proposed to explain high-frequency oscillations, but the mechanisms that underlie slow oscillations are still unclear. Here, we show by means of analytical solutions and simulations that facilitating excitatory (E (f)) synapses onto interneurons in a neural network play a fundamental role, not only in shaping the frequency of slow oscillations, but also in determining the form of the up and down states observed in electrophysiological measurements. Short time constants and strong E (f) synapse-connectivity were found to induce rapid alternations between up and down states, whereas long time constants and weak E (f) synapse connectivity prolonged the time between up states and increased the up state duration. These results suggest a novel role for facilitating excitatory synapses onto interneurons in controlling the form and frequency of slow oscillations in neuronal circuits.

Sleep after learning aids memory recall

Steffen Gais — 2007-11-18T18:18:51-00:00

Learn. Mem., Vol. 13, No. 3. (1 May 2006), pp. 259-262.

In recent years, the effect of sleep on memory consolidation has received considerable attention. In humans, these studies concentrated mainly on procedural types of memory, which are considered to be hippocampus-independent. Here, we show that sleep also has a persisting effect on hippocampus-dependent declarative memory. In two experiments, we examined high school students' ability to remember vocabulary. We show that declarative memory is enhanced when sleep follows within a few hours of learning, independent of time of day, and with equal amounts of interference during retention intervals. Sleep deprivation has a detrimental effect on memory, which was significant after a night of recovery sleep. Thus, fatigue accumulating during wake intervals could be ruled out as a confound. 10.1101/lm.132106

Combined blockade of cholinergic receptors shifts the brain from stimulus encoding to memory consolidation.

BH Rasch — 2008-07-23T14:41:34-00:00

Journal of cognitive neuroscience, Vol. 18, No. 5. (May 2006), pp. 793-802.

High central nervous system levels of acetylcholine (ACh) are commonly regarded as crucial for learning and memory, and a decline in cholinergic neurotransmission is associated with Alzheimer's dementia. However, recent findings revealed exceptions to this rule: The low ACh tone characterizing slow wave sleep (SWS) has proven necessary for consolidation of hippocampus-dependent declarative memories during this sleep stage. Such observations, together with recent models of a hippocampal-neocortical dialogue underlying systems memory consolidation, suggest that high levels of ACh support memory encoding, whereas low levels facilitate consolidation. We tested this hypothesis in human subjects by blocking cholinergic neurotransmission during wakefulness, starting 30 min after learning. Subjects received the muscarinic antagonist scopolamine (4 microg/kg bodyweight intravenously) and the nicotinic antagonist mecamylamine (5 mg orally). Compared to placebo, combined muscarinic and nicotinic receptor blockade significantly improved consolidation of declarative memories tested 10 hr later, but simultaneously impaired acquisition of similar material. Consolidation of procedural memories, which are not dependent on hippocampal functioning, was unaffected. Neither scopolamine nor mecamylamine alone enhanced declarative memory consolidation. Our findings support the notion that ACh acts as a switch between modes of acquisition and consolidation. We propose that the natural shift in central nervous system cholinergic tone from high levels during wakefulness to minimal levels during SWS optimizes declarative memory consolidation during a period with no need for new memory encoding.

Odor Cues During Slow-Wave Sleep Prompt Declarative Memory Consolidation

Bjorn Rasch — 2007-03-19T16:56:44-00:00

Science, Vol. 315, No. 5817. (9 March 2007), pp. 1426-1429.

Sleep facilitates memory consolidation. A widely held model assumes that this is because newly encoded memories undergo covert reactivation during sleep. We cued new memories in humans during sleep by presenting an odor that had been presented as context during prior learning, and so showed that reactivation indeed causes memory consolidation during sleep. Re-exposure to the odor during slow-wave sleep (SWS) improved the retention of hippocampus-dependent declarative memories but not of hippocampus-independent procedural memories. Odor re-exposure was ineffective during rapid eye movement sleep or wakefulness or when the odor had been omitted during prior learning. Concurring with these findings, functional magnetic resonance imaging revealed significant hippocampal activation in response to odor re-exposure during SWS. 10.1126/science.1138581

The neurobiology of consolidations, or, how stable is the engram?

Y Dudai — 2008-07-23T14:30:14-00:00

Annual review of psychology, Vol. 55 (2004), pp. 51-86.

Consolidation is the progressive postacquisition stabilization of long-term memory. The term is commonly used to refer to two types of processes: synaptic consolidation, which is accomplished within the first minutes to hours after learning and occurs in all memory systems studied so far; and system consolidation, which takes much longer, and in which memories that are initially dependent upon the hippocampus undergo reorganization and may become hippocampal-independent. The textbook account of consolidation is that for any item in memory, consolidation starts and ends just once. Recently, a heated debate has been revitalized on whether this is indeed the case, or, alternatively, whether memories become labile and must undergo some form of renewed consolidation every time they are activated. This debate focuses attention on fundamental issues concerning the nature of the memory trace, its maturation, persistence, retrievability, and modifiability.

Synaptic influence of hippocampus on pyramidal cells of the rat prefrontal cortex: an in vivo intracellular recording study.

E Dégenètais — 2008-07-21T09:25:23-00:00

Cerebral cortex (New York, N.Y. : 1991), Vol. 13, No. 7. (July 2003), pp. 782-792.

The hippocampus and prefrontal cortex are two structures implicated in learning and memory and are related through a direct excitatory pathway. The characteristics of the synaptic influence of the hippocampus on pyramidal cells of the prefrontal cortex were determined using intracellular recordings in anesthetized rats. Single-pulse stimulation of the hippocampus induced an early EPSP of fixed latency in most of the recorded pyramidal cells (n = 106/116) thereby demonstrating a monosynaptic connection between hippocampal neurons and pyramidal cells of the prefrontal cortex. Furthermore, the EPSP was followed by a prolonged IPSP and suggests a simultaneous engagement of pyramidal and non-pyramidal neurons that may ultimately constrain the spread of excitation in response to hippocampal input. Paired-pulse stimulation induced short-term modifications in the synaptic responses and this short-term plasticity may contribute to the temporal filtering of information. Finally, tetanic stimulation of the hippocampus produced long-term potentiation of the monosynaptic EPSP with a concomitant potentiation of the IPSP, indicating that the hippocampo-prefrontal network can participate in the formation and consolidation of memories. In conclusion, the characteristics of the synaptic transmission in the hippocampo-prefrontal cortex pathway further supports the existence of a cooperative relationship between two structures known to be involved in higher cognitive processes.

Reversal of LTP in the hippocampal afferent fiber system to the prefrontal cortex in vivo with low-frequency patterns of stimulation that do not produce LTD.

F Burette — 2008-07-21T09:23:31-00:00

Journal of neurophysiology, Vol. 78, No. 2. (August 1997), pp. 1155-1160.

We examined the efficacy of several patterns of low-frequency stimulation for producing long-term depression (LTD) or depotentiation in the hippocampal fiber pathway to the prefrontal cortex in the anesthetized rat. Field potentials elicited by stimulation of the CA1/subicular region of the ventral hippocampus were recorded in the prelimbic area of the prefrontal cortex. We found no evidence that low-frequency trains (0.5-1 Hz), consisting of either single pulses, paired pulses (35-ms interpulse interval), or two-pulse bursts (5-ms interval), produce LTD in the prefrontal cortex. In contrast, all three stimulus protocols were found to induce a small-amplitude, persistent potentiation of the amplitude of the negative wave of the field response recorded in the prefrontal cortex. We also examined the ability of patterns of low-frequency stimulation to produce depotentiation of previously established long-term potentiation (LTP). Although low-frequency stimulation with single pulses or paired pulses was ineffective, we found that the two-pulse burst protocol selectively produced a rapid reversal of LTP in the hippocampo-prefrontal cortex pathway. Depotentiation is reversible and can be induced >2 h after the induction of LTP. Repeated trains failed to decrease the prefrontal cortex response below the original, unpotentiated level. These findings demonstrate the existence of a depotentiation mechanism that is capable of exerting powerful control over ongoing or recently induced synaptic plasticity in hippocampocortical connections in vivo.

Long-term potentiation in the prefrontal cortex following stimulation of the hippocampal CA1/subicular region.

S Laroche — 2008-07-21T09:09:55-00:00

Neuroscience letters, Vol. 114, No. 2. (3 July 1990), pp. 184-190.

We have examined single cell activity and field potentials in the prelimbic area of the prefrontal cortex of the rat to electrical stimulation of the CA1/subicular region of the temporal hippocampus. Excitatory unit responses were found in 50 out of 120 neurons recorded in the prelimbic area. Paired-pulse facilitation was found for both single cell responses and field potentials. High-frequency, tetanic stimulation of the temporal hippocampus produced a significant and persistent potentiation of prelimbic field potentials. The evidence suggests that the direct pathway from the temporal hippocampus to the prelimbic area of the prefrontal cortex in the rat is excitatory and can undergo long-term potentiation (LTP).

Paired-pulse facilitation and depression at unitary synapses in rat hippocampus: quantal fluctuation affects subsequent release.

D Debanne — 2005-10-13T04:07:28-00:00

J Physiol, Vol. 491 ( Pt 1) (15 February 1996), pp. 163-176.

1. Excitatory synaptic transmission between pairs of monosynaptically coupled pyramidal cells was examined in rat hippocampal slice cultures. Action potentials were elicited in single CA3 pyramidal cells impaled with microelectrodes and unitary excitatory postsynaptic currents (EPSCs) were recorded in whole-cell voltage-clamped CA1 or CA3 cells. 2. The amplitude of successive unitary EPSCs in response to single action potentials varied. The amplitude of EPSCs was altered by adenosine or changes in the [Mg2+]/[CA2+] ratio. We conclude that single action potentials triggered the release of multiple quanta of glutamate. 3. When two action potentials were elicited in the presynaptic cell, the amplitude of the second EPSC was inversely related to the amplitude of the first. Paired-pulse facilitation (PPF) was observed when the first EPSC was small, i.e. the second EPSC was larger than the first, whereas paired-pulse depression (PPD) was observed when the first EPSC was large. 4. The number of trials displaying PPD was greater when release probability was increased, and smaller when release probability was decreased. 5. PPD was not postsynaptically mediated because it was unaffected by decreasing ionic flux with 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) or receptor desensitization with aniracetam. 6. PPF was maximal at an interstimulus interval of 70 ms and recovered within 500 ms. Recovery from PPD occurred within 5 s. 7. We propose that multiple release sites are formed by the axon of a CA3 pyramidal cell and a single postsynaptic CA1 or CA3 cell. PPF is observed if the first action potential fails to release transmitter at most release sites. PPD is observed if the first action potential successfully triggers release at most release sites. 8. Our observations of PPF are consistent with the residual calcium hypothesis. We conclude that PPD results from a decrease in quantal content, perhaps due to short-term depletion of readily releasable vesicles.

Frequency-dependent shift from paired-pulse facilitation to paired-pulse depression at unitary CA3-CA3 synapses in the rat hippocampus.

C Saviane — 2008-07-21T09:07:08-00:00

The Journal of physiology, Vol. 544, No. Pt 2. (15 October 2002), pp. 469-476.

Paired recordings between CA3 interconnected pyramidal neurons were used to study the properties of short-term depression occurring in these synapses under different frequencies of presynaptic firing (n = 22). In stationary conditions (0.05-0.067 Hz) pairs of presynaptic action potentials (50 ms apart) evoked EPSCs whose amplitude fluctuated from trial to trial with occasional response failures. In 15/20 cells, paired-pulse ratio (PPR) was characterized by facilitation (PPF) while in the remaining five by depression (PPD). Increasing stimulation frequency from 0.05-0.067 Hz to 0.1-1 Hz induced low frequency depression (LFD) of EPSC amplitude with a gradual increase in the failure rate. Overall, 9/12 cells at 1 Hz became almost "silent". In six cells in which the firing rate was sequentially shifted from 0.05 to 0.1 and 1 Hz, changes in synaptic efficacy were so strong that PPR shifted from PPF to PPD. The time course of depression of EPSC1 could be fitted with single exponentials with time constants of 98 and 36 s at 0.1 and 1 Hz, respectively. In line with the inversion of PPR at 1 Hz, the time course of depression of EPSC2 was faster than EPSC1 (7 s). Recovery from depression could be obtained by lowering the frequency of stimulation to 0.025 Hz. These results could be explained by a model that takes into account two distinct release processes, one dependent on the residual calcium and the other on the size of the readily releasable pool of vesicles.

Modulation of synaptic transmission and long-term potentiation: effects on paired pulse facilitation and EPSC variance in the CA1 region of the hippocampus.

T Manabe — 2005-10-11T18:55:32-00:00

J Neurophysiol, Vol. 70, No. 4. (October 1993), pp. 1451-1459.

1. Whole-cell patch-clamp recordings of excitatory postsynaptic currents (EPSCs) were made from guinea pig hippocampal CA1 pyramidal cells. The sensitivity of paired pulse facilitation (PPF) and EPSC variance to changes in synaptic transmission was investigated and the results were compared with the changes in these parameters evoked by long-term potentiation (LTP). 2. Presynaptic manipulations, such as activation of presynaptic gamma-aminobutyric acid-B receptors by baclofen, blockade of presynaptic adenosine receptors by theophylline, blockade of presynaptic potassium channels by cesium, and increasing the Ca(2+)-Mg2+ ratio in the external recording solution, each reliably changed PPF in a fashion reciprocal to the change in the EPSC amplitude. However, recruitment of additional synaptic release sites by increasing stimulus strength and antagonism of non-N-methyl-D-aspartate (NMDA) glutamate receptors by 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) failed to alter PPF. 3. Presynaptic manipulations including increased stimulus strength gave the predicted changes in the value of mean 2/variance (M2/sigma 2). Moreover, postsynaptic manipulations that altered EPSC amplitude, including blockade of non-NMDA receptors by CNQX, or changing the holding potential of the postsynaptic cell, gave little change in M2/sigma 2, as would be predicted for manipulations resulting in a uniform postsynaptic change. 4. LTP caused no change in PPF, whereas the presynaptic manipulations, which caused a similar amount of potentiation to that induced by LTP, significantly decreased PPF. On the other hand, LTP did increase M2/sigma 2, although the increase was less than that predicted for a purely presynaptic mechanism.(ABSTRACT TRUNCATED AT 250 WORDS)

Firing Rate Dynamics in the Hippocampus Induced by Trajectory Learning

Daoyun Ji — 2008-05-02T09:18:17-00:00

J. Neurosci., Vol. 28, No. 18. (30 April 2008), pp. 4679-4689.

The hippocampus is essential for spatial navigation, which may involve sequential learning. However, how the hippocampus encodes new sequences in familiar environments is unknown. To study the impact of novel spatial sequences on the activity of hippocampal neurons, we monitored hippocampal ensembles while rats learned to switch from two familiar trajectories to a new one in a familiar environment. Here, we show that this novel spatial experience induces two types of changes in firing rates, but not locations of hippocampal place cells. First, place-cell firing rates on the two familiar trajectories start to change before the actual behavioral switch to the new trajectory. Second, repeated exposure on the new trajectory is associated with an increased dependence of place-cell firing rates on immediate past locations. The result suggests that sequence encoding in the hippocampus may involve integration of information about the recent past into current state. 10.1523/JNEUROSCI.4597-07.2008

Cellular and Network Mechanisms of Slow Oscillatory Activity (<1 Hz) and Wave Propagations in a Cortical Network Model

Albert Compte — 2008-05-05T17:43:26-00:00

J Neurophysiol, Vol. 89, No. 5. (1 May 2003), pp. 2707-2725.

Compte, Albert, Maria V. Sanchez-Vives, David A. McCormick, and Xiao-Jing Wang. Cellular and Network Mechanisms of Slow Oscillatory Activity (<1 Hz) and Wave Propagations in a Cortical Network Model. J. Neurophysiol. 89: 2707-2725, 2003. Slow oscillatory activity (<1 Hz) is observed in vivo in the cortex during slow-wave sleep or under anesthesia and in vitro when the bath solution is chosen to more closely mimic cerebrospinal fluid. Here we present a biophysical network model for the slow oscillations observed in vitro that reproduces the single neuron behaviors and collective network firing patterns in control as well as under pharmacological manipulations. The membrane potential of a neuron oscillates slowly (at <1 Hz) between a down state and an up state; the up state is maintained by strong recurrent excitation balanced by inhibition, and the transition to the down state is due to a slow adaptation current (Na+-dependent K+ current). Consistent with in vivo data, the input resistance of a model neuron, on average, is the largest at the end of the down state and the smallest during the initial phase of the up state. An activity wave is initiated by spontaneous spike discharges in a minority of neurons, and propagates across the network at a speed of 3-8 mm/s in control and 20-50 mm/s with inhibition block. Our work suggests that long-range excitatory patchy connections contribute significantly to this wave propagation. Finally, we show with this model that various known physiological effects of neuromodulation can switch the network to tonic firing, thus simulating a transition to the waking state. 10.1152/jn.00845.2002

Hyperpolarization-activated graded persistent activity in the prefrontal cortex.

M Winograd — 2008-06-27T17:30:10-00:00

Proceedings of the National Academy of Sciences of the United States of America, Vol. 105, No. 20. (20 May 2008), pp. 7298-7303.

We describe a phenomenon of hyperpolarization-activated graded persistent activity (HAGPA) in prefrontal cortex neurons. Successive hyperpolarizing pulses induced increasingly higher rates of tonic firing that remained stable for tens of seconds, allowing the neuron to retain a memory of the previous history of stimulation. This phenomenon occurred at the cellular level and in the absence of neuromodulators. Neurons with HAGPA had a sag during hyperpolarization, and blocking h-current eliminated the sag and prevented HAGPA, suggesting that the activation of this hyperpolarization-activated cationic current was necessary for the occurrence of the phenomenon. A single-neuron biophysical model including h-current modulation by intracellular calcium was able to display HAGPA. This form of neuronal memory not only allows the transformation of inhibition into an increase of firing rate, but also endows neurons with a mechanism to compute the properties of successive inputs into persistent activity, thus solving a difficult computational problem.

Synaptic transmission and plasticity in an active cortical network.

R Reig — 2008-06-27T17:29:29-00:00

PLoS ONE, Vol. 2, No. 7. (2007)

BACKGROUND: The cerebral cortex is permanently active during both awake and sleep states. This ongoing cortical activity has an impact on synaptic transmission and short-term plasticity. An activity pattern generated by the cortical network is a slow rhythmic activity that alternates up (active) and down (silent) states, a pattern occurring during slow wave sleep, anesthesia and even in vitro. Here we have studied 1) how network activity affects short term synaptic plasticity and, 2) how synaptic transmission varies in up versus down states. METHODOLOGY/PRINCIPAL FINDINGS: Intracellular recordings obtained from cortex in vitro and in vivo were used to record synaptic potentials, while presynaptic activation was achieved either with electrical or natural stimulation. Repetitive activation of layer 4 to layer 2/3 synaptic connections from ferret visual cortex slices displayed synaptic augmentation that was larger and longer lasting in active than in silent slices. Paired-pulse facilitation was also significantly larger in an active network and it persisted for longer intervals (up to 200 ms) than in silent slices. Intracortical synaptic potentials occurring during up states in vitro increased their amplitude while paired-pulse facilitation disappeared. Both intracortical and thalamocortical synaptic potentials were also significantly larger in up than in down states in the cat visual cortex in vivo. These enhanced synaptic potentials did not further facilitate when pairs of stimuli were given, thus paired-pulse facilitation during up states in vivo was virtually absent. Visually induced synaptic responses displayed larger amplitudes when occurring during up versus down states. This was further tested in rat barrel cortex, where a sensory activated synaptic potential was also larger in up states. CONCLUSIONS/SIGNIFICANCE: These results imply that synaptic transmission in an active cortical network is more secure and efficient due to larger amplitude of synaptic potentials and lesser short term plasticity.

Quick Simultaneous Confidence Intervals for Multinomial Proportions

Simon Fitzpatrick — 2008-06-25T14:59:56-00:00

Journal of the American Statistical Association, Vol. 82, No. 399. (1987), pp. 875-878.

Opinion polls often give an indication of sampling error based on the standard conservative confidence intervals for a single binomial proportion. We give a lower bound for the simultaneous coverage probability when such intervals are applied to all of the proportions in a poll. This bound is equal to 1 - 2α for small values of α. The same result is shown to apply to the standard confidence intervals for changes in proportions between surveys.

Preferential Reactivation of Motivationally Relevant Information in the Ventral Striatum

Carien Lansink — 2008-06-18T18:22:40-00:00

J. Neurosci., Vol. 28, No. 25. (18 June 2008), pp. 6372-6382.

Spontaneous "off-line" reactivation of neuronal activity patterns may contribute to the consolidation of memory traces. The ventral striatum exhibits reactivation and has been implicated in the processing of motivational information. It is unknown, however, whether reactivating neuronal ensembles specifically recapitulate information relating to rewards that were encountered during wakefulness. We demonstrate a prolonged reactivation in rat ventral striatum during quiet wakefulness and slow-wave but not rapid eye movement sleep. Reactivation of reward-related information processed in this structure was particularly prominent, and this was primarily attributable to spike trains temporally linked to reward sites. It was accounted for by small, strongly correlated subgroups in recorded cell assemblies and can thus be characterized as a sparse phenomenon. Our results indicate that reactivated memory traces may not only comprise feature- and context-specific information but also contain a value component. 10.1523/JNEUROSCI.1054-08.2008

Spatial representations of hippocampal CA1 neurons are modulated by behavioral context in a hippocampus-dependent memory task.

AL Griffin — 2008-06-12T10:10:23-00:00

The Journal of neuroscience : the official journal of the Society for Neuroscience, Vol. 27, No. 9. (28 February 2007), pp. 2416-2423.

Although it is well known that hippocampal neurons code spatial information, it is less clear how these spatial representations are influenced by memory demands, especially in hippocampus-dependent tasks. Recently, our laboratory has demonstrated that hippocampal spatial representations are influenced by mnemonic factors in a T-maze continuous alternation task. Another unique experimental approach that might reveal the ways in which task-related factors impact hippocampal spatial representations is to compare firing patterns between events that require distinct episodic memory processes. Therefore, we recorded from CA1 single neurons during a discrete trial delayed-nonmatch-to-place task that allowed within-trial comparison between an encoding (sample) phase and a retrieval (choice) phase. A large subset of neurons that fired on the central stem of the maze showed dramatic selectivity for either the sample or choice phase of the trial. However, surprisingly, there were fewer neurons that showed differential firing rates between left- and right-bound trajectories. Our results suggest that trial-phase-selective coding is common in tasks that require rapid alternation between encoding and retrieval processes.

Temporal Frequency of Subthreshold Oscillations Scales with Entorhinal Grid Cell Field Spacing

Lisa Giocomo — 2007-03-23T21:59:27-00:00

Science, Vol. 315, No. 5819. (23 March 2007), pp. 1719-1722.

Grid cells in layer II of rat entorhinal cortex fire to spatial locations in a repeating hexagonal grid, with smaller spacing between grid fields for neurons inmore dorsal anatomical locations. Data from in vitro whole-cell patch recordings showed differences in frequency of subthreshold membrane potential oscillations in entorhinal neurons that correspond to different positions along the dorsal-to-ventral axis, supporting a model of physiological mechanisms for grid cell responses. 10.1126/science.1139207

Grid cell firing may arise from interference of theta frequency membrane potential oscillations in single neurons.

ME Hasselmo — 2008-06-12T10:07:59-00:00

Hippocampus, Vol. 17, No. 12. (2007), pp. 1252-1271.

Intracellular recording and computational modelling suggest that interactions of subthreshold membrane potential oscillation frequency in different dendritic branches of entorhinal cortex stellate cells could underlie the functional coding of continuous dimensions of space and time. Among other things, these interactions could underlie properties of grid cell field spacing. The relationship between experimental data on membrane potential oscillation frequency (f) and grid cell field spacing (G) indicates a constant scaling factor H = fG. This constant scaling factor between temporal oscillation frequency and spatial periodicity provides a starting constraint that is used to derive the model of Burgess et al. (Hippocampus, 2007). This model provides a consistent quantitative link between single cell physiological properties and properties of spiking units in awake behaving animals. Further properties and predictions of this model about single cell and network physiological properties are analyzed. In particular, the model makes quantitative predictions about the change in membrane potential, single cell oscillation frequency, and network oscillation frequency associated with speed of movement, about the independence of single cell properties from network theta rhythm oscillations, and about the effect of variations in initial oscillatory phase on the pattern of grid cell firing fields. These same mechanisms of subthreshold oscillations may play a more general role in memory function, by providing a method for learning arbitrary time intervals in memory sequences.

Reversed and forward buffering of behavioral spike sequences enables retrospective and prospective retrieval in hippocampal regions CA3 and CA1.

RA Koene — 2008-06-12T10:05:41-00:00

Neural networks : the official journal of the International Neural Network Society, Vol. 21, No. 2-3. (r 2008), pp. 276-288.

We propose a mechanism to explain both retrospective and prospective recall activity found in experimental data from hippocampal regions CA3 and CA1. Our model of temporal context dependent episodic memory replicates reverse recall in CA1, as recently recorded and published [Foster, D., & Wilson, M. (2006). Reverse replay of behavioural sequences in hippocampal place cells during the awake state. Nature, 440, 680-683], as well as the prospective and retrospective activity recorded in region CA3 during spatial tasks [Johnson, A., & Redish, A. (2006). Neural ensembles in ca3 transiently encode paths forward of the animal at a decision point: a possible mechanism for the consideration of alternatives. In 2006 neuroscience meeting planner. Atlanta, GA: Society for Neuroscience. (Program no. 574.2)]. We suppose that CA3 encodes episodic memory of both forward and reversed sequences of perforant path spikes representing place input. Using a persistent firing buffer mechanism in layer II of entorhinal cortex, simulated episodic learning involves dentate gyrus, layer III of entorhinal cortex, and hippocampal regions CA3 and CA1. Associations are formed between buffered episodic cues, unique temporal context specific representations in dentate gyrus, and episodic memory in the CA3 recurrent network.

Theta-Mediated Dynamics of Spatial Information in Hippocampus -- et al. 28 (23): 5959 -- Journal of Neuroscience

Itskov — 2008-06-11T20:39:29-00:00

Activity-dependent decrease of excitability in rat hippocampal neurons through increases in Ih

Yuan Fan — 2005-10-27T05:37:50-00:00

Nature Neuroscience, Vol. 8, No. 11. (23 October 2005), pp. 1542-1551.

Long-term potentiation in rat hippocampal neurons is accompanied by spatially widespread changes in intrinsic oscillatory dynamics and excitability.

R Narayanan — 2008-06-11T20:04:11-00:00

Neuron, Vol. 56, No. 6. (20 December 2007), pp. 1061-1075.

Oscillations in neural activity are a prominent feature of many brain states. Individual hippocampal neurons exhibit intrinsic membrane potential oscillations and intrinsic resonance in the theta frequency range. We found that the subthreshold resonance frequency of CA1 pyramidal neurons was location dependent, varying more than 3-fold between the soma and the distal dendrites. Furthermore, activity- and NMDA-receptor-dependent long-term plasticity increased this resonance frequency through changes in h channel properties. The increase in resonance frequency and an associated reduction in excitability were nearly identical in the soma and the first 300 mum of the apical dendrites. These spatially widespread changes accompanying long-term synaptic potentiation also reduced the neuron's ability to elicit spikes evoked through a nonpotentiated synaptic pathway. Our results suggest that the frequency response of these neurons depends on the dendritic location of their inputs and that activity can regulate their response dynamics within an oscillating neural network.

The h channel mediates location dependence and plasticity of intrinsic phase response in rat hippocampal neurons.

R Narayanan — 2008-06-11T20:03:54-00:00

The Journal of neuroscience : the official journal of the Society for Neuroscience, Vol. 28, No. 22. (28 May 2008), pp. 5846-5850.

The presence of phenomenological inductances in neuronal membrane has been known for more than one-half a century. Despite this, the dramatic contributions of such inductive elements to the amplitude and, especially, phase of neuronal impedance, and their roles in modulating temporal dynamics of neuronal responses have surprisingly remained unexplored. In this study, we demonstrate that the h channel contributes a location-dependent and plastic phenomenological inductive component to the input impedance of CA1 pyramidal neurons. Specifically, we show that the h channels introduce an apparent negative delay in the local voltage response of these neurons with respect to the injected current within the theta frequency range. The frequency range and the extent of this lead expand with increases in h current either through hyperpolarization, or with increasing distance of dendritic location from the soma. We also demonstrate that a spatially widespread increase in this inductive phase component accompanies long-term potentiation. Finally, using impedance analysis, we show that both location and activity dependence of intrinsic phase response are attributable not to changes in a capacitive or a leak component, but to changes in h-channel properties. Our results suggest that certain voltage-gated ion channels can differentially regulate internal time delays within neurons, thus providing them with an independent control mechanism in temporal coding of neuronal information. Our analyses and results also establish impedance as a powerful measure of intrinsic dynamics and excitability, given that it quantifies temporal relationships among signals and excitability as functions of input frequency.

Noradrenergic, but not cholinergic, deafferentation of prefrontal cortex impairs attentional set-shifting.

J McGaughy — 2008-06-02T18:02:01-00:00

Neuroscience, Vol. 153, No. 1. (22 April 2008), pp. 63-71.

Both norepinephrine and acetylcholine have been shown to be critically involved in mediating attention but there remains debate about whether they serve similar or unique functions. Much of what is known about the role of these neurochemicals in cognition is based on manipulations done at the level of the cell body but these findings are difficult to reconcile with data regarding the unique contribution of cortical subregions, e.g. the dorsolateral prefrontal cortex, to attention. In the current study, we directly compared the effects of noradrenergic and cholinergic deafferentation of the rat medial prefrontal cortex, the homologue of primate dorsolateral prefrontal cortex, using an intradimensional/extradimensional attentional set shifting task, a task previously shown to be able to dissociate the function of the primate dorsolateral prefrontal cortex from orbitofrontal cortex. We found that noradrenergic, but not cholinergic, deafferentation produces specific impairments in the ability to shift attentional set. We also clarified the nature of the attentional deficits by assessing the ability of rats to disregard irrelevant stimuli. Noradrenergic lesions did not alter the ability of rats to ignore irrelevant stimuli, suggesting that the attentional deficit results from an overly focused attentional state that retards learning that a new stimulus dimension predicts reward.

Prefrontal cortical modulation of acetylcholine release in posterior parietal cortex.

CL Nelson — 2008-06-02T17:58:29-00:00

Neuroscience, Vol. 132, No. 2. (2005), pp. 347-359.

Attentional processing is a crucial early stage in cognition and is subject to "top-down" regulation by prefrontal cortex (PFC). Top-down regulation involves modification of input processing in cortical and subcortical areas, including the posterior parietal cortex (PPC). Cortical cholinergic inputs, originating from the basal forebrain cholinergic system, have been demonstrated to mediate important aspects of attentional processing. The present study investigated the ability of cholinergic and glutamatergic transmission within PFC to regulate acetylcholine (ACh) release in PPC. The first set of experiments demonstrated increases in ACh efflux in PPC following AMPA administration into the PFC. These increases were antagonized by co-administration of the AMPA receptor antagonist DNQX into the PFC. The second set of experiments demonstrated that administration of carbachol, but not nicotine, into the PFC also increased ACh efflux in PPC. The effects of carbachol were attenuated by co-administration (into PFC) of a muscarinic antagonist (atropine) and partially attenuated by the nicotine antagonist mecamylamine and DNQX. Perfusion of carbachol, nicotine, or AMPA into the PPC did not affect PFC ACh efflux, suggesting that these cortical interactions are not bi-directional. These studies demonstrate the capacity of the PFC to regulate ACh release in the PPC via glutamatergic and cholinergic prefrontal mechanisms. Prefrontal regulation of ACh release elsewhere in the cortex is hypothesized to contribute to the cognitive optimization of input processing.

More attention must be paid: the neurobiology of attentional effort.

M Sarter — 2006-10-09T23:18:52-00:00

Brain Res Brain Res Rev, Vol. 51, No. 2. (August 2006), pp. 145-160.

Increases in attentional effort are defined as the motivated activation of attentional systems in response to detrimental challenges on attentional performance, such as the presentation of distractors, prolonged time-on-task, changing target stimulus characteristics and stimulus presentation parameters, circadian phase shifts, stress or sickness. Increases in attentional effort are motivated by the expected performance outcome; in the absence of such motivation, attentional performance continues to decline or may cease altogether. The beneficial effects of increased attentional effort are due in part to the activation of top-down mechanisms that act to optimize input detection and processing, thereby stabilizing or recovering attentional performance in response to challenges. Following a description of the psychological construct "attentional effort", evidence is reviewed indicating that increases in the activity of cortical cholinergic inputs represent a major component of the neuronal circuitry mediating increases in attentional effort. A neuronal model describes how error detection and reward loss, indicating declining performance, are integrated with motivational mechanisms on the basis of neuronal circuits between prefrontal/anterior cingulate and mesolimbic regions. The cortical cholinergic input system is activated by projections of mesolimbic structures to the basal forebrain cholinergic system. In prefrontal regions, increases in cholinergic activity are hypothesized to contribute to the activation of the anterior attention system and associated executive functions, particularly the top-down optimization of input processing in sensory regions. Moreover, and influenced in part by prefrontal projections to the basal forebrain, increases in cholinergic activity in sensory and other posterior cortical regions contribute directly to the modification of receptive field properties or the suppression of contextual information and, therefore, to the mediation of top-down effects. The definition of attentional effort as a cognitive incentive, and the description of a neuronal circuitry model that integrates brain systems involved in performance monitoring, the processing of incentives, activation of attention systems and modulation of input functions, suggest that 'attentional effort' represents a viable construct for cognitive neuroscience research.

Prefrontal Acetylcholine Release Controls Cue Detection on Multiple Timescales

Vinay Parikh — 2007-10-12T09:59:56-00:00

Neuron, Vol. 56, No. 1. (4 October 2007), pp. 141-154.

Summary Cholinergic neurons originating from the basal forebrain innervate the entire cortical mantle. Choline-sensitive microelectrodes were used to measure the synaptic release of cortical acetylcholine (ACh) at a subsecond resolution in rats performing a task involving the detection of cues. Cues that were detected, defined behaviorally, evoked transient increases in cholinergic activity (at the scale of seconds) in the medial prefrontal cortex (mPFC), but not in a nonassociational control region (motor cortex). In trials involving missed cues, cholinergic transients were not observed. Cholinergic deafferentation of the mPFC, but not motor cortex, impaired cue detection. Furthermore, decreases and increases in precue cholinergic activity predicted subsequent cue detection or misses, respectively. Finally, cue-evoked cholinergic transients were superimposed over slower (at the timescale of minutes) changes in cholinergic activity. Cortical cholinergic neurotransmission is regulated on multiple timescales to mediate the detection of behaviorally significant cues and to support cognitive performance.

Sleep directly following learning benefits consolidation of spatial associative memory.

LM Talamini — 2008-05-24T10:08:49-00:00

Learning & memory (Cold Spring Harbor, N.Y.), Vol. 15, No. 4. (2008), pp. 233-237.

The last decade has brought forth convincing evidence for a role of sleep in non-declarative memory. A similar function of sleep in episodic memory is supported by various correlational studies, but direct evidence is limited. Here we show that cued recall of face-location associations is significantly higher following a 12-h retention interval containing sleep than following an equally long period of waking. Furthermore, retention is significantly higher over a 24-h sleep-wake interval than over an equally long wake-sleep interval. This difference occurs because retention during sleep was significantly better when sleep followed learning directly, rather than after a day of waking. These data demonstrate a beneficial effect of sleep on memory that cannot be explained solely as a consequence of reduced interference. Rather, our findings suggest a competitive consolidation process, in which the fate of a memory depends, at least in part, on its relative stability at sleep onset: Strong memories tend to be preserved, while weaker memories erode still further. An important aspect of memory consolidation may thus result from the removal of irrelevant memory "debris."

Sustained increase in hippocampal sharp-wave ripple activity during slow-wave sleep after learning.

O Eschenko — 2008-05-24T10:06:27-00:00

Learning & memory (Cold Spring Harbor, N.Y.), Vol. 15, No. 4. (2008), pp. 222-228.

High-frequency oscillations, known as sharp-wave/ripple (SPW-R) complexes occurring in hippocampus during slow-wave sleep (SWS), have been proposed to promote synaptic plasticity necessary for memory consolidation. We recorded sleep for 3 h after rats were trained on an odor-reward association task. Learning resulted in an increased number SPW-Rs during the first hour of post-learning SWS. The magnitude of ripple events and their duration were also elevated for up to 2 h after the newly formed memory. Rats that did not learn the discrimination during the training session did not show any change in SPW-Rs. Successful retrieval from remote memory was likewise accompanied by an increase in SPW-R density and magnitude, relative to the previously recorded baseline, but the effects were much shorter lasting and did not include increases in ripple duration and amplitude. A short-lasting increase of ripple activity was also observed when rats were rewarded for performing a motor component of the task only. There were no increases in ripple activity after habituation to the experimental environment. These experiments show that the characteristics of hippocampal high-frequency oscillations during SWS are affected by prior behavioral experience. Associative learning induces robust and sustained (up to 2 h) changes in several SPW-R characteristics, while after retrieval from remote memory or performance of a well-trained procedural aspect of the task, only transient changes in ripple density were induced.

Both the Hippocampus and Striatum Are Involved in Consolidation of Motor Sequence Memory

Geneviève Albouy — 2008-04-25T12:12:01-00:00

Neuron, Vol. 58, No. 2. (24 April 2008), pp. 261-272.

Summary Functional magnetic resonance imaging (fMRI) was used to investigate the cerebral correlates of motor sequence memory consolidation. Participants were scanned while training on an implicit oculomotor sequence learning task and during a single testing session taking place 30 min, 5 hr, or 24 hr later. During training, responses observed in hippocampus and striatum were linearly related to the gain in performance observed overnight, but not over the day. Responses in both structures were significantly larger at 24 hr than at 30 min or 5 hr. Additionally, the competitive interaction observed between these structures during training became cooperative overnight. These results stress the importance of both hippocampus and striatum in procedural memory consolidation. Responses in these areas during training seem to condition the overnight memory processing that is associated with a change in their functional interactions. These results show that both structures interact during motor sequence consolidation to optimize subsequent behavior.

Astrocytic involvement in learning and memory consolidation.

Marie E Gibbs — 2008-05-24T10:04:09-00:00

Neuroscience and biobehavioral reviews (27 March 2008)

Astrocytes play fundamental roles in brain function, interacting with neurons and other astrocytes, yet their role in learning is not widely recognized. This review focuses on astrocytic involvement in memory consolidation following bead discrimination learning in day-old chick and draws parallels to mammalian learning, providing strong empirical support for the conclusion that the described neuronal-astrocytic interactions are universally valid. It identifies specific mechanisms whereby astrocytes support memory consolidation. Uptake of glucose, stimulated in astrocytes by beta(3)-noradrenergic receptor activation, provides energy by glycolytic/oxidative metabolism. Unlike neurons, astrocytes carry out net synthesis of tricarboxylic acid cycle intermediates needed for synthesis of transmitter glutamate formed by rapid degradation of glucose-derived glycogen and stimulated by beta(2)-noradrenergic receptor activation. This makes learning dependent on glycogenolysis and its stimulation by noradrenaline. Astrocytes take up most synaptically released glutamate, terminating transmitter activity and returning glutamate to neurons in a glutamate-glutamine cycle, interference with which abolishes learning. The various astrocytic activities follow a rigidly controlled time schedule, easily determined after bead discrimination learning but also detectable in other paradigms.

A double dissociation of subcortical hippocampal efferents for encoding and consolidation/retrieval of spatial information.

Michael R Hunsaker — 2008-05-24T10:02:25-00:00

Hippocampus (20 May 2008)

CA3 lesions impair encoding, whereas CA1 lesions impair retrieval during learning of a Hebb-Williams maze. CA3 efferents in the fimbria were transected, taking care to spare cholinergic and GABAergic afferents. CA1 efferents in the dorsal fornix were similarly transected. Fimbria transections, but not dorsal fornix transections, resulted in deficits for the encoding of spatial information during learning of a Hebb-Williams maze. Dorsal fornix, but not fimbria, transections resulted in deficits for retrieval of spatial memory during learning of a Hebb-Williams maze. These results reveal a double dissociation for the roles of CA3 and CA1 subcortical efferents in encoding and retrieval processes that mirror the double dissociation seen after excitotoxic lesions of CA1 and CA3. These data provide support for the theory that the cholinergic projections from the septal nuclei modulate the dynamics for encoding and consolidation/retrieval in the hippocampus. (c) 2008 Wiley-Liss, Inc.

Visual-Procedural Memory Consolidation during Sleep Blocked by Glutamatergic Receptor Antagonists

Steffen Gais — 2008-05-22T20:07:44-00:00

J. Neurosci., Vol. 28, No. 21. (21 May 2008), pp. 5513-5518.

Visual cortex plasticity is enhanced by sleep. It is hypothesized that a reactivation of glutamatergic synapses is essential for this form of plasticity to occur after learning. To test this hypothesis, human subjects practiced a visual texture discrimination skill known to require post-training sleep for improvements to occur. During sleep, glutamatergic transmission was inhibited by administration of the two glutamate antagonists, caroverine and ketamine, targeting the ionotropic NMDA and AMPA receptors. Both substances given during consolidation sleep in a placebo controlled crossover design were able to prevent improvement of the skill measured the next morning. An off-line activation of glutamatergic synapses therefore seems to play a critical part in the consolidation of plastic changes in the visual cortex. 10.1523/JNEUROSCI.5374-07.2008

Causal Reasoning in Rats

Aaron Blaisdell — 2006-02-17T09:42:04-00:00

Science, Vol. 311, No. 5763. (17 February 2006), pp. 1020-1022.

Empirical research with nonhuman primates appears to support the view that causal reasoning is a key cognitive faculty that divides humans from animals. The claim is that animals approximate causal learning using associative processes. The present results cast doubt on that conclusion. Rats made causal inferences in a basic task that taps into core features of causal reasoning without requiring complex physical knowledge. They derived predictions of the outcomes of interventions after passive observational learning of different kinds of causal models. These competencies cannot be explained by current associative theories but are consistent with causal Bayes net theories.

Coding and learning of behavioral sequences

Ofer Melamed — 2008-05-07T16:58:00-00:00

Trends in Neurosciences, Vol. 27, No. 1. (January 2004), pp. 11-14.

A major challenge to understanding behavior is how the nervous system allows the learning of behavioral sequences that can occur over arbitrary timescales, ranging from milliseconds up to seconds, using a fixed millisecond learning rule. This article describes some potential solutions, and then focuses on a study by Mehta et al. that could contribute towards solving this puzzle. They have discovered that an experience-dependent asymmetric shape of hippocampal receptive fields combined with oscillatory inhibition can serve to map behavioral sequences on a fixed timescale.

The function of dream sleep.

F Crick — 2008-05-06T09:09:41-00:00

Nature, Vol. 304, No. 5922. (0 1983), pp. 111-114.

We propose that the function of dream sleep (more properly rapid-eye movement or REM sleep) is to remove certain undesirable modes of interaction in networks of cells in the cerebral cortex. We postulate that this is done in REM sleep by a reverse learning mechanism (see also p. 158), so that the trace in the brain of the unconscious dream is weakened, rather than strengthened, by the dream.

Inverse temporal contributions of the dorsal hippocampus and medial prefrontal cortex to the expression of long-term fear memories.

JJ Quinn — 2008-05-06T09:02:12-00:00

Learning & memory (Cold Spring Harbor, N.Y.), Vol. 15, No. 5. (2008), pp. 368-372.

Retrograde amnesia following disruptions of hippocampal function is often temporally graded, with recent memories being more impaired. Evidence supports the existence of one or more neocortical long-term memory storage/retrieval site(s). Neurotoxic lesions of the medial prefrontal cortex (mPFC) or the dorsal hippocampus (DH) were made 1 day or 200 days following trace fear conditioning. Recently encoded trace fear memories were most disrupted by DH lesions, while remotely encoded trace and contextual memories were most disrupted by mPFC lesions. These data strongly support the consolidation theory of hippocampus function and implicate the mPFC as a site of long-term memory storage/retrieval.

Valuations for spike train prediction.

V Itskov — 2008-04-28T13:41:52-00:00

Neural computation, Vol. 20, No. 3. (March 2008), pp. 644-667.

The ultimate product of an electrophysiology experiment is often a decision on which biological hypothesis or model best explains the observed data. We outline a paradigm designed for comparison of different models, which we refer to as spike train prediction. A key ingredient of this paradigm is a prediction quality valuation that estimates how close a predicted conditional intensity function is to an actual observed spike train. Although a valuation based on log likelihood (L) is most natural, it has various complications in this context. We propose that a quadratic valuation (Q) can be used as an alternative to L. Q shares some important theoretical properties with L, including consistency, and the two valuations perform similarly on simulated and experimental data. Moreover, Q is more robust than L, and optimization with Q can dramatically improve computational efficiency. We illustrate the utility of Q for comparing models of peer prediction, where it can be computed directly from cross-correlograms. Although Q does not have a straightforward probabilistic interpretation, Q is essentially given by Euclidean distance.

Theta phase-specific codes for two-dimensional position, trajectory and heading in the hippocampus

John Huxter — 2008-04-25T13:57:55-00:00

Nat Neurosci, Vol. 11, No. 5. (May 2008), pp. 587-594.

Ventral Tegmental Area Afferents to the Prefrontal Cortex Maintain Membrane Potential `Up' States in Pyramidal Neurons via D1 Dopamine Receptors

BL Lewis — 2008-04-24T12:13:15-00:00

Cerebral Cortex (December 2000), pp. 1168-1175.

The electrophysiological nature of dopamine actions has been controversial for years, with data supporting both inhibitory and excitatory actions. In this study, we tested whether stimulation of the ventral tegmental area (VTA), the source of the dopamine innervation of the prefrontal cortex, would exert different responses depending on the membrane potential states that pyramidal neurons exhibit when recorded in vivo, and whether VTA stimulation would have a role in controlling transitions between these states. Prefrontal cortical neurons have a very negative resting membrane potential (down state) interrupted by plateau depolarizations (up state). Although the up state had been shown to be dependent on hippocampal afferents in nucleus accumbens neurons, our results indicate that neither hippocampal nor thalamic inputs are sufficient to drive up events in prefrontal cortical neurons. Electrical VTA stimulation resulted in a variety of actions, in many cases depending on the neuron membrane potential state. Trains of stimuli resembling burst firing evoked a long-lasting transition to the up state, an effect blocked by a D1 antagonist and mimicked by chemical VTA stimulation. These results indicate that projections from the VTA to the prefrontal cortex may be involved in controlling membrane potential states that define assemblies of activable pyramidal neurons in this region.

D2 dopamine receptors recruit a GABA component for their attenuation of excitatory synaptic transmission in the adult rat prefrontal cortex.

KY Tseng — 2008-04-24T12:10:16-00:00

Synapse (New York, N.Y.), Vol. 61, No. 10. (October 2007), pp. 843-850.

The dopamine modulation of neuronal excitability in the prefrontal cortex (PFC) changes during critical late periods of postnatal development. In particular, D2 receptors activate fast-spiking interneurons after, and not before, adolescence. To test the functional impact of this change, we investigated the effects of dopamine agonists on PFC excitatory synaptic transmission with whole-cell recordings from deep-layer pyramidal neurons in brain slices obtained from prepubertal [postnatal day (PD) 28-35] and postpubertal (PD>51) rats. Electrical stimulation of superficial layers elicited a fast AMPA/kainate excitatory postsynaptic potential (EPSP). In the adult PFC, the D2 agonist quinpirole decreased EPSP amplitude, an effect that lasted for at least 25 min after drug washout and was blocked by the D2 antagonist eticlopride. The late component of this effect was blocked by the GABA-A antagonist picrotoxin without affecting the early inhibition. Quinpirole also decreased EPSP amplitude in deep-layer pyramidal neurons from prepubertal rats, but this response was not affected by picrotoxin. A D1 agonist, on the other hand, did not affect the pyramidal neuron EPSP. These results indicate that D2, not D1, receptors attenuate local excitatory synaptic transmission in the adult PFC, and this effect of D2 involves a recruitment of local GABAergic activity.

Glutamate released from glial cells synchronizes neuronal activity in the hippocampus.

MC Angulo — 2008-04-15T09:52:54-00:00

The Journal of neuroscience : the official journal of the Society for Neuroscience, Vol. 24, No. 31. (4 August 2004), pp. 6920-6927.

Glial cells of the nervous system directly influence neuronal and synaptic activities by releasing transmitters. However, the physiological consequences of this glial transmitter release on brain information processing remain poorly understood. We demonstrate here in hippocampal slices of 2- to 5-week-old rats that glutamate released from glial cells generates slow transient currents (STCs) mediated by the activation of NMDA receptors in pyramidal cells. STCs persist in the absence of neuronal and synaptic activity, indicating a nonsynaptic origin of the source of glutamate. Indeed, STCs occur spontaneously but can also be induced by pharmacological tools known to activate astrocytes and by the selective mechanical stimulation of single nearby glial cells. Bath application of the inhibitor of the glutamate uptake dl-threo-beta-benzyloxyaspartate increases both the frequency of STCs and the amplitude of a tonic conductance mediated by NMDA receptors and probably also originated from glial glutamate release. By using dual recordings, we observed synchronized STCs in pyramidal cells having their soma distant by <100 microm. The degree of precision (<100 msec) of this synchronization rules out the involvement of calcium waves spreading through the glial network. It also indicates that single glial cells release glutamate onto adjacent neuronal processes, thereby controlling simultaneously the excitability of several neighboring pyramidal cells. In conclusion, our results show that the glial glutamate release occurs spontaneously and synchronizes the neuronal activity in the hippocampus.

Hemodynamic cerebral correlates of sleep spindles during human non-rapid eye movement sleep

M Schabus — 2007-08-07T17:37:19-00:00

PNAS, Vol. 104, No. 32. (7 August 2007), pp. 13164-13169.

In humans, some evidence suggests that there are two different types of spindles during sleep, which differ by their scalp topography and possibly some aspects of their regulation. To test for the existence of two different spindle types, we characterized the activity associated with slow (1113 Hz) and fast (1315 Hz) spindles, identified as discrete events during non-rapid eye movement sleep, in non-sleep-deprived human volunteers, using simultaneous electroencephalography and functional MRI. An activation pattern common to both spindle types involved the thalami, paralimbic areas (anterior cingulate and insular cortices), and superior temporal gyri. No thalamic difference was detected in the direct comparison between slow and fast spindles although some thalamic areas were preferentially activated in relation to either spindle type. Beyond the common activation pattern, the increases in cortical activity differed significantly between the two spindle types. Slow spindles were associated with increased activity in the superior frontal gyrus. In contrast, fast spindles recruited a set of cortical regions involved in sensorimotor processing, as well as the mesial frontal cortex and hippocampus. The recruitment of partially segregated cortical networks for slow and fast spindles further supports the existence of two spindle types during human non-rapid eye movement sleep, with potentially different functional significance. 10.1073/pnas.0703084104

Essential Role of D1 But Not D2 Receptors in the NMDA Receptor-Dependent Long-Term Potentiation at Hippocampal-Prefrontal Cortex Synapses In Vivo

Hirac Gurden — 2008-04-10T09:36:20-00:00

J. Neurosci., Vol. 20, No. 22. (15 November 2000), 106RC.

An intact mesocortical dopaminergic (DA) input to the prefrontal cortex (PFC) has been reported to be necessary for long-term potentiation (LTP) to occur at hippocampal-prefrontal cortex synapses. Here, we investigated the role of D1 and D2 receptors in this NMDA receptor-dependent LTP. Local infusion of the D1 agonist SKF81297 at an optimal dose induced a sustained enhancement of hippocampal-PFC LTP, whereas the D1 antagonist SCH23390 caused a dose-related impairment of its induction. The D1 agonist effect was mimicked by infusion of a low dose of the adenylyl cyclase activator forskolin, whereas LTP was severely attenuated with a protein kinase A inhibitor, Rp-cAMPS. To further assess the complex interplay between DA and NMDA receptors, changes in extracellular DA levels in the PFC were estimated during LTP, and a significant increase was observed immediately after tetanus. Taken together, these data suggest that D1 but not D2 receptors are crucial for the DA control of the NMDA receptor-mediated synaptic response on a specific excitatory input to the PFC. The interactions of these receptors may play a crucial role in the storage and transfer of hippocampal information in the PFC.

NMDA Receptor-dependent Long-term Potentiation in the Hippocampal Afferent Fibre System to the Prefrontal Cortex in the Rat

Therese Jay — 2008-04-10T09:30:30-00:00

European Journal of Neuroscience, Vol. 7, No. 2. (1995), pp. 247-250.

Abstract This study investigated the role of the N-methyl-d-aspartate (NMDA) subtype of glutamate receptor in the induction of long-term potentiation (LTP) in the hippocampal-prefrontal cortex pathway in vivo. Field potentials evoked by electrical stimulation of the CA1/subicular region were recorded in the prelimbic area of the prefrontal cortex under continuous perfusion of artificial cerebrospinal fluid in anaesthetized rats. High-frequency stimulation of the CA1/subicular region induced LTP of the evoked response in the prelimbic area of the prefrontal cortex. LTP was completely blocked when the selective NMDA receptor antagonist d-(-)2-amino-5- phosphonopentanoic acid (d-AP5; 200 muM), was perfused during the tetanus. Perfusion of D-AP5 did not affect normal transmission or pre-established LTP. These results demonstrate that induction of LTP in the hippocampal-prefrontal cortex pathway is an NMDA receptor-dependent process.