CiteULike: nelmor's library [327 articles]

Reward-Dependent Modulation of Neuronal Activity in the Primate Dorsal Raphe Nucleus

Kae Nakamura — 2008-05-14T17:09:11-00:00

J. Neurosci., Vol. 28, No. 20. (14 May 2008), pp. 5331-5343.

The dopamine system has been thought to play a central role in guiding behavior based on rewards. Recent pharmacological studies suggest that another monoamine neurotransmitter, serotonin, is also involved in reward processing. To elucidate the functional relationship between serotonin neurons and dopamine neurons, we performed single-unit recording in the dorsal raphe nucleus (DRN), a major source of serotonin, and the substantia nigra pars compacta, a major source of dopamine, while monkeys performed saccade tasks in which the position of the target indicated the size of an upcoming reward. After target onset, but before reward delivery, the activity of many DRN neurons was modulated tonically by the expected reward size with either large- or small-reward preference, whereas putative dopamine neurons had phasic responses and only preferred large rewards. After reward delivery, the activity of DRN neurons was modulated tonically by the received reward size with either large- or small-reward preference, whereas the activity of dopamine neurons was not modulated except after the unexpected reversal of the position-reward contingency. Thus, DRN neurons encode the expected and received rewards, whereas dopamine neurons encode the difference between the expected and received rewards. These results suggest that the DRN, probably including serotonin neurons, signals the reward value associated with the current behavior. 10.1523/JNEUROSCI.0021-08.2008

Analysis of Between-Trial and Within-Trial Neural Spiking Dynamics

Gabriela Czanner — 2008-05-14T09:52:24-00:00

J Neurophysiol, Vol. 99, No. 5. (1 May 2008), pp. 2672-2693.

Recording single-neuron activity from a specific brain region across multiple trials in response to the same stimulus or execution of the same behavioral task is a common neurophysiology protocol. The raster plots of the spike trains often show strong between-trial and within-trial dynamics, yet the standard analysis of these data with the peristimulus time histogram (PSTH) and ANOVA do not consider between-trial dynamics. By itself, the PSTH does not provide a framework for statistical inference. We present a state-space generalized linear model (SS-GLM) to formulate a point process representation of between-trial and within-trial neural spiking dynamics. Our model has the PSTH as a special case. We provide a framework for model estimation, model selection, goodness-of-fit analysis, and inference. In an analysis of hippocampal neural activity recorded from a monkey performing a location-scene association task, we demonstrate how the SS-GLM may be used to answer frequently posed neurophysiological questions including, What is the nature of the between-trial and within-trial task-specific modulation of the neural spiking activity? How can we characterize learning-related neural dynamics? What are the timescales and characteristics of the neuron's biophysical properties? Our results demonstrate that the SS-GLM is a more informative tool than the PSTH and ANOVA for analysis of multiple trial neural responses and that it provides a quantitative characterization of the between-trial and withintrial neural dynamics readily visible in raster plots, as well as the less apparent fast (1-10 ms), intermediate (11-20 ms), and longer (>20 ms) timescale features of the neuron's biophysical properties. 10.1152/jn.00343.2007

Value Representations in the Primate Striatum during Matching Behavior

Brian Lau — 2008-05-08T09:40:23-00:00

Neuron, Vol. 58, No. 3. (8 May 2008), pp. 451-463.

Summary Choosing the most valuable course of action requires knowing the outcomes associated with the available alternatives. The striatum may be important for representing the values of actions. We examined this in monkeys performing an oculomotor choice task. The activity of phasically active neurons (PANs) in the striatum covaried with two classes of information: action-values and chosen-values. Action-value PANs were correlated with value estimates for one of the available actions, and these signals were frequently observed before movement execution. Chosen-value PANs were correlated with the value of the action that had been chosen, and these signals were primarily observed later in the task, immediately before or persistently after movement execution. These populations may serve distinct functions mediated by the striatum: some PANs may participate in choice by encoding the values of the available actions, while other PANs may participate in evaluative updating by encoding the reward value of chosen actions.

Artificial dural sealant that allows multiple penetrations of implantable brain probes

Nathan Jackson — 2008-05-02T09:35:28-00:00

Journal of Neuroscience Methods, Vol. 171, No. 1. (15 June 2008), pp. 147-152.

This study reports extensive characterization of the silicone gel (3-4680, Dow Corning, Midland, MI), for potential use as an artificial dural sealant in long-term electrophysiological experiments in neurophysiology. Dural sealants are important to preserve the integrity of the intracranial space after a craniotomy and in prolonging the lifetime and functionality of implanted brain probes. In this study, we report results of our tests on a commercially available silicone gel with unique properties that make it an ideal dural substitute. The substitute is transparent, elastic, easy to apply, and has re-sealing capabilities, which makes it desirable for applications where multiple penetrations by the brain probe is desirable over an extended period of time. Cytotoxicity tests (for up to 10 days) with fibroblasts and in vivo tests (for 12 weeks) show that the gel is non-toxic and does not produce any significant neuronal degeneration when applied to the rodent cortex even after 12 weeks. In vivo humidity testing showed no sign of CSF leakage for up to 6 weeks. The gel also allows silicon microprobes to penetrate with forces less than 0.5 mN, and a 200-[mu]m diameter stainless steel microprobe with a blunt tip to penetrate with a force less than 2.5 mN. The force dependency on the velocity of penetration and thickness of the gel was also quantified and empirically modeled. The above results demonstrate that the silicone gel (3-4680) can be a viable dural substitute in long-term electrophysiology of the brain.

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

Disrupted Dopamine Transmission and the Emergence of Exaggerated Beta Oscillations in Subthalamic Nucleus and Cerebral Cortex

Nicolas Mallet — 2008-05-02T08:52:58-00:00

J. Neurosci., Vol. 28, No. 18. (30 April 2008), pp. 4795-4806.

In the subthalamic nucleus (STN) of Parkinson's disease (PD) patients, a pronounced synchronization of oscillatory activity at beta frequencies (15-30 Hz) accompanies movement difficulties. Abnormal beta oscillations and motor symptoms are concomitantly and acutely suppressed by dopaminergic therapies, suggesting that these inappropriate rhythms might also emerge acutely from disrupted dopamine transmission. The neural basis of these abnormal beta oscillations is unclear, and how they might compromise information processing, or how they arise, is unknown. Using a 6-hydroxydopamine-lesioned rodent model of PD, we demonstrate that beta oscillations are inappropriately exaggerated, compared with controls, in a brain-state-dependent manner after chronic dopamine loss. Exaggerated beta oscillations are expressed at the levels of single neurons and small neuronal ensembles, and are focally present and spatially distributed within STN. They are also expressed in synchronous population activities, as evinced by oscillatory local field potentials, in STN and cortex. Excessively synchronized beta oscillations reduce the information coding capacity of STN neuronal ensembles, which may contribute to parkinsonian motor impairment. Acute disruption of dopamine transmission in control animals with antagonists of D1/D2 receptors did not exaggerate STN or cortical beta oscillations. Moreover, beta oscillations were not exaggerated until several days after 6-hydroxydopamine injections. Thus, contrary to predictions, abnormally amplified beta oscillations in cortico-STN circuits do not result simply from an acute absence of dopamine receptor stimulation, but are instead delayed sequelae of chronic dopamine depletion. Targeting the plastic processes underlying the delayed emergence of pathological beta oscillations after continuing dopaminergic dysfunction may offer considerable therapeutic promise. 10.1523/JNEUROSCI.0123-08.2008

A metric for odorant comparison

Rafi Haddad — 2008-04-30T10:23:32-00:00

Nat Meth, Vol. 5, No. 5. (May 2008), pp. 425-429.

Low-Serotonin Levels Increase Delayed Reward Discounting in Humans

Nicolas Schweighofer — 2008-04-24T13:04:57-00:00

J. Neurosci., Vol. 28, No. 17. (23 April 2008), pp. 4528-4532.

Previous animal experiments have shown that serotonin is involved in the control of impulsive choice, as characterized by high preference for small immediate rewards over larger delayed rewards. Previous human studies under serotonin manipulation, however, have been either inconclusive on the effect on impulsivity or have shown an effect in the speed of action-reward learning or the optimality of action choice. Here, we manipulated central serotonergic levels of healthy volunteers by dietary tryptophan depletion and loading. Subjects performed a "dynamic" delayed reward choice task that required a continuous update of the reward value estimates to maximize total gain. By using a computational model of delayed reward choice learning, we estimated the parameters governing the subjects' reward choices in low-, normal, and high-serotonin conditions. We found an increase of proportion in small reward choices, together with an increase in the rate of discounting of delayed rewards in the low-serotonin condition compared with the control and high-serotonin conditions. There were no significant differences between conditions in the speed of learning of the estimated delayed reward values or in the variability of reward choice. Therefore, in line with previous animal experiments, our results show that low-serotonin levels steepen delayed reward discounting in humans. The combined results of our previous and current studies suggest that serotonin may adjust the rate of delayed reward discounting via the modulation of specific loops in parallel corticobasal ganglia circuits. 10.1523/JNEUROSCI.4982-07.2008

Lateral presynaptic inhibition mediates gain control in an olfactory circuit

Shawn Olsen — 2008-03-18T04:25:40-00:00

Nature (16 March 2008)

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.

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.

Decoupling through Synchrony in Neuronal Circuits with Propagation Delays

Evgueniy Lubenov — 2008-04-10T12:05:30-00:00

Neuron, Vol. 58, No. 1. (10 April 2008), pp. 118-131.

Summary The level of synchronization in distributed systems is often controlled by the strength of the interactions between individual elements. In brain circuits the connection strengths between neurons are modified under the influence of spike-timing-dependent plasticity (STDP) rules. Here we show that when recurrent networks with conduction delays exhibit population bursts, STDP rules exert a strong decoupling force that desynchronizes activity. Conversely, when activity in the network is random, the same rules can have a coupling and synchronizing influence. The presence of these opposing forces promotes the self-organization of spontaneously active neuronal networks to a state at the border between randomness and synchrony. The decoupling force of STDP may be engaged by the synchronous bursts occurring in the hippocampus during slow-wave sleep, leading to the selective erasure of information from hippocampal circuits as memories are established in neocortical areas.

Fear Conditioning and Extinction Differentially Modify the Intrinsic Excitability of Infralimbic Neurons

Edwin Santini — 2008-04-09T17:07:30-00:00

J. Neurosci., Vol. 28, No. 15. (9 April 2008), pp. 4028-4036.

Extinction of conditioned fear is an active learning process involving inhibition of fear expression. It has been proposed that fear extinction potentiates neurons in the infralimbic (IL) prefrontal cortex, but the cellular mechanisms underlying this potentiation remain unknown. It is also not known whether this potentiation occurs locally in IL neurons as opposed to IL afferents. To determine whether extinction enhances the intrinsic excitability of IL pyramidal neurons in layers II/III and V, we performed whole-cell patch-clamp recordings in slices from naive, conditioned, or conditioned-extinguished rats. We observed that conditioning depressed IL excitability compared with slices from naive animals, as evidenced by a decreased number of spikes evoked by injected current and an increase in the slow afterhyperpolarizing potential (sAHP). Extinction reversed these conditioning-induced effects. Furthermore, IL neurons from extinguished rats showed increased burst spiking compared with naive rats, which was correlated with extinction recall. These changes were specific to IL prefrontal cortex and were not observed in prelimbic prefrontal cortex. Together, these findings suggest that IL intrinsic excitability is reduced to allow for expression of conditioning memory and enhanced for expression of extinction memory through the modulation of Ca2+-gated K+ channels underlying the sAHP. Inappropriate modulation of these intrinsic mechanisms may underlie anxiety disorders, characterized by exaggerated fear and deficient extinction. 10.1523/JNEUROSCI.2623-07.2008

A common neurobiology for pain and pleasure

Siri Leknes — 2008-03-21T04:33:30-00:00

Nature Reviews Neuroscience, Vol. 9, No. 4., pp. 314-320.

Memory influences on hippocampal and striatal neural codes: effects of a shift between task rules.

O Eschenko — 2008-02-18T11:15:55-00:00

Neurobiol Learn Mem, Vol. 87, No. 4. (May 2007), pp. 495-509.

Interactions with neocortical memory systems may facilitate flexible information processing by hippocampus. We sought direct evidence for such memory influences by recording hippocampal neural responses to a change in cognitive strategy. Well-trained rats switched (within a single recording session) between the use of place and response strategies to solve a plus maze task. Maze and extramaze environments were constant throughout testing. Place fields demonstrated (in-field) firing rate and location-based reorganization [Leutgeb, S., Leutgeb, J. K., Barnes, C. A., Moser, E. I., McNaughton, B. L., & Moser, M. B. (2005). Independent codes for spatial and episodic memory in hippocampal neuronal ensembles. Science, 309, 619-623] after a task switch, suggesting that hippocampus encoded each phase of testing as a different context, or episode. The task switch also resulted in qualitative and quantitative changes to discharge that were correlated with an animal's velocity or acceleration of movement. Thus, the effects of a strategy switch extended beyond the spatial domain, and the movement correlates were not passive reflections of the current behavioral state. To determine whether hippocampal neural responses were unique, striatal place and movement-correlated neurons were simultaneously recorded with hippocampal neurons. Striatal place and movement cells exhibited a response profile that was similar, but not identical, to that observed for hippocampus after a strategy switch. Thus, retrieval of a different memory led both neural systems to represent a different context. However, hippocampus may play a special (though not exclusive) role in flexible spatial processing since correlated firing amongst cell pairs was highest when rats successfully switched between two spatial tasks. Correlated firing by striatal cell pairs increased following any strategy switch, supporting the view that striatum codes change in reinforcement contingencies.

Relationships between place cell firing fields and navigational decisions by rats.

PP Lenck-Santini — 2008-03-31T12:22:57-00:00

J Neurosci, Vol. 22, No. 20. (15 October 2002), pp. 9035-9047.

This study examined the performance of spatial problems by rats when purely behavioral manipulations disturb the relationship between the place cell representation and the cues used to solve the problems. Place cells were recorded while rats performed a task in which they had to locate a goal in a gray cylinder. In the "far" task, the unmarked goal was displaced by a large fixed distance from a white card on the cylinder wall. In the "near" task, the unmarked goal was directly in front of the card. Finally, in the "cue" task the goal was marked by a black disk on the cylinder floor. Relationships between visible stimuli and place cell activity were manipulated by conducting either "hidden" (with the rat in its home cage) or "visible" (with the rat in the recording apparatus) rotations of the wall card and, when present, independent rotations of the black disk. Hidden card rotations generally caused equal firing field rotations, whereas visible card rotations often did not cause fields to move. In the far task, visible card rotations were associated with a strong decrease of correct responses in the card-referred goal area. Most rats tended to search the goal in the field-referred area. In the near task, visible card rotations were associated with a moderate decrease of performance, with rats searching the goal at the wall card. Finally, field placements had no effect on performance in the cue task. Thus, visible rotations tended to disrupt the relationship between firing fields and cues in all tasks but impaired performance only in the task that required map-based navigation. These results provide strong new evidence in favor of the spatial mapping theory of hippocampal function.

Episodic-Like Memory in Rats: Is It Based on When or How Long Ago?

William Roberts — 2008-04-04T09:21:08-00:00

Science, Vol. 320, No. 5872. (4 April 2008), pp. 113-115.

Recent experiments with rats suggest that they show episodic-like or what-where-when memory for a preferred food found on a radial maze. Although memory for when a salient event occurred suggests that rats can mentally travel in time to a moment in the past, an alternative possibility is that they remember how long ago the food was found. Three groups of rats were tested for memory of previously encountered food. The different groups could use only the cues of when, how long ago, or when + how long ago. Only the cue of how long ago food was encountered was used successfully. These results suggest that episodic-like memory in rats is qualitatively different from human episodic memory. 10.1126/science.1152709

Characterizing synaptic conductance fluctuations in cortical neurons and their influence on spike generation

Zuzanna Piwkowska — 2008-04-01T11:29:51-00:00

Journal of Neuroscience Methods, Vol. 169, No. 2. (30 April 2008), pp. 302-322.

Cortical neurons are subject to sustained and irregular synaptic activity which causes important fluctuations of the membrane potential (Vm). We review here different methods to characterize this activity and its impact on spike generation. The simplified, fluctuating point-conductance model of synaptic activity provides the starting point of a variety of methods for the analysis of intracellular Vm recordings. In this model, the synaptic excitatory and inhibitory conductances are described by Gaussian-distributed stochastic variables, or "colored conductance noise". The matching of experimentally recorded Vm distributions to an invertible theoretical expression derived from the model allows the extraction of parameters characterizing the synaptic conductance distributions. This analysis can be complemented by the matching of experimental Vm power spectral densities (PSDs) to a theoretical template, even though the unexpected scaling properties of experimental PSDs limit the precision of this latter approach. Building on this stochastic characterization of synaptic activity, we also propose methods to qualitatively and quantitatively evaluate spike-triggered averages of synaptic time-courses preceding spikes. This analysis points to an essential role for synaptic conductance variance in determining spike times. The presented methods are evaluated using controlled conductance injection in cortical neurons in vitro with the dynamic-clamp technique. We review their applications to the analysis of in vivo intracellular recordings in cat association cortex, which suggest a predominant role for inhibition in determining both sub- and supra-threshold dynamics of cortical neurons embedded in active networks.

Dopamine-dependent interactions between limbic and prefrontal cortical plasticity in the nucleus accumbens: disruption by cocaine sensitization.

Y Goto — 2008-03-31T08:33:26-00:00

Neuron, Vol. 47, No. 2. (21 July 2005), pp. 255-266.

The prefrontal cortex and the hippocampus exhibit converging projections to the nucleus accumbens and have functional reciprocal connections via indirect pathways. As a result, information processing between these structures is likely to be bidirectional. Using evoked potential measures, we examined the interactions of these inputs on synaptic plasticity within the accumbens. Our results show that the direction of information flow between the prefrontal cortex and limbic structures determines the synaptic plasticity that these inputs exhibit within the accumbens. Moreover, this synaptic plasticity at hippocampal and prefrontal inputs selectively involves dopamine D1 and D2 activation or inactivation, respectively. Repeated cocaine administration disrupted this synaptic plasticity at hippocampal and prefrontal cortical inputs and goal-directed behavior in the spatial maze task. Thus, interactions of limbic-prefrontal cortical synaptic plasticity and its dysfunction within the accumbens could underlie complex information processing deficits observed in individuals following psychostimulant administration.

Dopaminergic modulation of limbic and cortical drive of nucleus accumbens in goal-directed behavior

Yukiori Goto — 2005-05-25T19:50:13-00:00

Nature Neuroscience, Vol. 8, No. 6. (22 May 2005), pp. 805-812.

Rule Learning by Rats

Robin Murphy — 2008-03-28T11:03:44-00:00

Science, Vol. 319, No. 5871. (28 March 2008), pp. 1849-1851.

Using rules extracted from experience to solve problems in novel situations involves cognitions such as analogical reasoning and language learning and is considered a keystone of humans' unique abilities. Nonprimates, it has been argued, lack such rule transfer. We report that Rattus norvegicus can learn simple rules and apply them to new situations. Rats learned that sequences of stimuli consistent with a rule (such as XYX) were different from other sequences (such as XXY or YXX). When novel stimuli were used to construct sequences that did or did not obey the previously learned rule, rats transferred their learning. Therefore, rats, like humans, can transfer structural knowledge from sequential experiences. 10.1126/science.1151564

Electric Fields Due to Synaptic Currents Sharpen Excitatory Transmission

Sergiy Sylantyev — 2008-03-28T10:51:59-00:00

Science, Vol. 319, No. 5871. (28 March 2008), pp. 1845-1849.

The synaptic response waveform, which determines signal integration properties in the brain, depends on the spatiotemporal profile of neurotransmitter in the synaptic cleft. Here, we show that electrophoretic interactions between AMPA receptormediated excitatory currents and negatively charged glutamate molecules accelerate the clearance of glutamate from the synaptic cleft, speeding up synaptic responses. This phenomenon is reversed upon depolarization and diminished when intracleft electric fields are weakened through a decrease in the AMPA receptor density. In contrast, the kinetics of receptor-mediated currents evoked by direct application of glutamate are voltage-independent, as are synaptic currents mediated by the electrically neutral neurotransmitter GABA. Voltage-dependent temporal tuning of excitatory synaptic responses may thus contribute to signal integration in neural circuits. 10.1126/science.1154330

Aversive Learning Enhances Perceptual and Cortical Discrimination of Indiscriminable Odor Cues

Wen Li — 2008-03-28T02:55:03-00:00

Science, Vol. 319, No. 5871. (28 March 2008), pp. 1842-1845.

Learning to associate sensory cues with threats is critical for minimizing aversive experience. The ecological benefit of associative learning relies on accurate perception of predictive cues, but how aversive learning enhances perceptual acuity of sensory signals, particularly in humans, is unclear. We combined multivariate functional magnetic resonance imaging with olfactory psychophysics to show that initially indistinguishable odor enantiomers (mirror-image molecules) become discriminable after aversive conditioning, paralleling the spatial divergence of ensemble activity patterns in primary olfactory (piriform) cortex. Our findings indicate that aversive learning induces piriform plasticity with corresponding gains in odor enantiomer discrimination, underscoring the capacity of fear conditioning to update perceptual representation of predictive cues, over and above its well-recognized role in the acquisition of conditioned responses. That completely indiscriminable sensations can be transformed into discriminable percepts further accentuates the potency of associative learning to enhance sensory cue perception and support adaptive behavior. 10.1126/science.1152837

Behavioral Phenotyping Strategies for Mutant Mice

Jacqueline Crawley — 2008-03-27T11:46:10-00:00

Neuron, Vol. 57, No. 6. (27 March 2008), pp. 809-818.

Comprehensive behavioral analyses of transgenic and knockout mice have successfully identified the functional roles of many genes in the brain. Over the past 10 years, strategies for mouse behavioral phenotyping have evolved to maximize the scope and replicability of findings from a cohort of mutant mice, minimize the interpretation of procedural artifacts, and provide robust translational tools to test hypotheses and develop treatments. This Primer addresses experimental design issues and offers examples of high-throughput batteries, learning and memory tasks, and anxiety-related tests.

Smokers' brains compute, but ignore, a fictive error signal in a sequential investment task

Pearl Chiu — 2008-03-27T04:34:10-00:00

Nature Neuroscience, Vol. 11, No. 4. (02 March 2008), pp. 514-520.

Neural correlates of perceptual learning in a sensory-motor, but not a sensory, cortical area.

Chi-Tat Law — 2008-03-17T17:04:07-00:00

Nat Neurosci (9 March 2008)

This study aimed to identify neural mechanisms that underlie perceptual learning in a visual-discrimination task. We trained two monkeys (Macaca mulatta) to determine the direction of visual motion while we recorded from their middle temporal area (MT), which in trained monkeys represents motion information that is used to solve the task, and lateral intraparietal area (LIP), which represents the transformation of motion information into a saccadic choice. During training, improved behavioral sensitivity to weak motion signals was accompanied by changes in motion-driven responses of neurons in LIP, but not in MT. The time course and magnitude of the changes in LIP correlated with the changes in behavioral sensitivity throughout training. Thus, for this task, perceptual learning does not appear to involve improvements in how sensory information is represented in the brain, but rather how the sensory representation is interpreted to form the decision that guides behavior.

Emotional environments retune the valence of appetitive versus fearful functions in nucleus accumbens

Sheila Reynolds — 2008-03-26T15:35:40-00:00

Nat Neurosci, Vol. 11, No. 4. (April 2008), pp. 423-425.

The Seductive Allure of Neuroscience Explanations

Deena Weisberg — 2008-02-16T10:05:06-00:00

J. Cogn. Neurosci., Vol. 20, No. 3. (1 March 2008), pp. 470-477.

Explanations of psychological phenomena seem to generate more public interest when they contain neuroscientific information. Even irrelevant neuroscience information in an explanation of a psychological phenomenon may interfere with people's abilities to critically consider the underlying logic of this explanation. We tested this hypothesis by giving naive adults, students in a neuroscience course, and neuroscience experts brief descriptions of psychological phenomena followed by one of four types of explanation, according to a 2 (good explanation vs. bad explanation) x 2 (without neuroscience vs. with neuroscience) design. Crucially, the neuroscience information was irrelevant to the logic of the explanation, as confirmed by the expert subjects. Subjects in all three groups judged good explanations as more satisfying than bad ones. But subjects in the two nonexpert groups additionally judged that explanations with logically irrelevant neuroscience information were more satisfying than explanations without. The neuroscience information had a particularly striking effect on nonexperts' judgments of bad explanations, masking otherwise salient problems in these explanations.

Integrating hippocampus and striatum in decision-making.

Adam Johnson — 2008-03-17T15:13:24-00:00

Curr Opin Neurobiol (27 February 2008)

Learning and memory and navigation literatures emphasize interactions between multiple memory systems: a flexible, planning-based system and a rigid, cached-value system. This has profound implications for decision-making. Recent conceptualizations of flexible decision-making employ prospection and projection arising from a network involving the hippocampus. Recent recordings from rodent hippocampus in decision-making situations have found transient forward-shifted representations. Evaluation of that prediction and subsequent action-selection probably occurs downstream (e.g. in orbitofrontal cortex, in ventral and dorsomedial striatum). Classically, striatum has been identified as a crucial component of the less-flexible, incremental system. Current evidence, however, suggests that striatum is involved in both flexible and stimulus-response decision-making, with dorsolateral striatum involved in stimulus-response strategies and ventral and dorsomedial striatum involved in goal-directed strategies.

Dynamic Ensemble Odor Coding in the Mammalian Olfactory Bulb: Sensory Information at Different Timescales

Brice Bathellier — 2008-02-28T13:45:55-00:00

Neuron, Vol. 57, No. 4. (28 February 2008), pp. 586-598.

Summary Neural firing discharges are often temporally patterned, but it is often ambiguous as to whether the temporal features of these patterns constitute a useful code. Here we show in the mouse olfactory bulb that ensembles of projection neurons respond with complex odor- and concentration-specific dynamic activity sequences developing below and above sniffing frequency. Based on this activity, almost optimal discrimination of presented odors was possible during single sniffs, consistent with reported behavioral data. Within a sniff cycle, slower features of the dynamics alone (>100 ms resolution, including mean firing rate) were sufficient for maximal discrimination. A smaller amount of information was also observed in faster features down to 20-40 ms resolution. Therefore, mitral cell ensemble activity contains information at different timescales that could be separately or complementarily exploited by downstream brain centers to make odor discriminations. Our results also support suggestive analogies in the dynamics of odor representations between insects and mammals.

Temporal compression mediated by short-term synaptic plasticity

Christian Leibold — 2008-03-17T10:49:54-00:00

Proceedings of the National Academy of Sciences (12 March 2008), 0708711105.

Time scales of cortical neuronal dynamics range from few milliseconds to hundreds of milliseconds. In contrast, behavior occurs on the time scale of seconds or longer. How can behavioral time then be neuronally represented in cortical networks? Here, using electrophysiology and modeling, we offer a hypothesis on how to bridge the gap between behavioral and cellular time scales. The core idea is to use a long time constant of decay of synaptic facilitation to translate slow behaviorally induced temporal correlations into a distribution of synaptic response amplitudes. These amplitudes can then be transferred to a sequence of action potentials in a population of neurons. These sequences provide temporal correlations on a millisecond time scale that are able to induce persistent synaptic changes. As a proof of concept, we provide simulations of a neuron that learns to discriminate temporal patterns on a time scale of seconds by synaptic learning rules with a millisecond memory buffer. We find that the conversion from synaptic amplitudes to millisecond correlations can be strongly facilitated by subthreshold oscillations both in terms of information transmission and success of learning. 10.1073/pnas.0708711105

Behavioral and Electrophysiological Indices of Negative Affect Predict Cocaine Self-Administration

Robert Wheeler — 2008-03-13T09:21:58-00:00

Neuron, Vol. 57, No. 5. (13 March 2008), pp. 774-785.

Summary The motivation to seek cocaine comes in part from a dysregulation of reward processing manifested in dysphoria, or affective withdrawal. Learning is a critical aspect of drug abuse; however, it remains unclear whether drug-associated cues can elicit the emotional withdrawal symptoms that promote cocaine use. Here we report that a cocaine-associated taste cue elicited a conditioned aversive state that was behaviorally and neurophysiologically quantifiable and predicted subsequent cocaine self-administration behavior. Specifically, brief intraoral infusions of a cocaine-predictive flavored saccharin solution elicited aversive orofacial responses that predicted early-session cocaine taking in rats. The expression of aversive taste reactivity also was associated with a shift in the predominant pattern of electrophysiological activity of nucleus accumbens (NAc) neurons from inhibitory to excitatory. The dynamic nature of this conditioned switch in affect and the neural code reveals a mechanism by which cues may exert control over drug self-administration.

Synaptic interactions among excitatory afferents to nucleus accumbens neurons: hippocampal gating of prefrontal cortical input.

P O'Donnell — 2008-03-12T13:00:07-00:00

J Neurosci, Vol. 15, No. 5 Pt 1. (May 1995), pp. 3622-3639.

The interactions among excitatory inputs arising from the prefrontal cortex, amygdala, and hippocampus, and innervating nucleus accumbens neurons were studied using in vivo intracellular recording techniques. Neurons recorded in the accumbens displayed one of three activity states: (1) silent, (2) spontaneously firing at low, constant rates, or (3) a bistable membrane potential, characterized by alternating periods of activity and silence occurring in concert with spontaneous transitions between two steady-state membrane potentials (average, -77.3 +/- 7.1 mV base, -63.0 +/- 7.4 mV plateau). These neurons also exhibited a high degree of convergence of responses elicited by stimulation of each of the three excitatory inputs tested. Activation of hippocampal afferents, but not cortical, amygdaloid, or thalamic afferents, induced bistable cells to switch to the depolarized (active) state. In contrast, no bistable cells were encountered in the nucleus accumbens following an acute transection of the fornix. Furthermore, microinjection of lidocaine in the vicinity of the hippocampal afferents at the level of the fornix caused a reversible elimination of the plateau phase in bistable cells. These data suggest that hippocampal input is necessary for accumbens neurons to enter a depolarized, active state. Furthermore, activation of prefrontal cortical inputs fail to evoke spike firing in accumbens neurons unless they are in this active state. Consequently, the hippocampus appears to be capable of gating prefrontal corticoaccumbens throughput.

A novel mouse brain slice preparation of the hippocampo-accumbens pathway.

RT Matthews — 2008-03-12T12:57:58-00:00

J Neurosci Methods, Vol. 137, No. 1. (15 August 2004), pp. 49-60.

The nucleus accumbens (NAc) is an important component of circuitry that underlies reward related behaviors and the rewarding properties of drugs of abuse. Glutamatergic afferents to the nucleus are critical for its normal function and for behaviors related to drug addiction. An angled, sagittal mouse brain slice preparation has been designed to facilitate concurrent stimulation of two major glutamatergic afferent pathways to the nucleus accumbens. Medium spiny neurons at the medial core/shell boundary of the accumbens were depolarized by stimulation of either hippocampal or limbic cortical afferents through activation of AMPA-type glutamate receptors. High frequency but not low frequency stimulation of hippocampal afferents depolarized medium spiny neurons to a membrane potential that resembled the up state observed upon high frequency stimulation in vivo. The magnitude of the membrane depolarization was positively correlated with the amplitude of the stimulus-evoked EPSP. Concurrent stimulation of hippocampal and limbic cortical afferents at theta frequency selectively induced a long-term depression (LTD) in the magnitude of stimulus-evoked EPSPs on the hippocampal afferent only. These data suggest that this brain slice preparation can be used to study mechanisms underlying synaptic plasticity at two of the critical glutamatergic afferent synapses in the nucleus accumbens as well as characterizing potential interactions between afferents. Additionally, LTD at hippocampo-accumbens synapses can be induced at a stimulus frequency known to support reinstatement of drug seeking behavior.

Dopamine Receptor Activation Is Required for Corticostriatal Spike-Timing-Dependent Plasticity

Verena Pawlak — 2008-03-06T14:16:09-00:00

J. Neurosci., Vol. 28, No. 10. (5 March 2008), pp. 2435-2446.

Single action potentials (APs) backpropagate into the higher-order dendrites of striatal spiny projection neurons during cortically driven "up" states. The timing of these backpropagating APs relative to the arriving corticostriatal excitatory inputs determines changes in dendritic calcium concentration. The question arises to whether this spike-timing relative to cortical excitatory inputs can also induce synaptic plasticity at corticostriatal synapses. Here we show that timing of single postsynaptic APs relative to the cortically evoked EPSP determines both the direction and the strength of synaptic plasticity in spiny projection neurons. Single APs occurring 30 ms before the cortically evoked EPSP induced long-term depression (LTD), whereas APs occurring 10 ms after the EPSP induced long-term potentiation (LTP). The amount of plasticity decreased as the time between the APs and EPSPs was increased, with the resulting spike-timing window being broader for LTD than for LTP. In addition, we show that dopamine receptor activation is required for this spike-timing-dependent plasticity (STDP). Blocking dopamine D1/D5 receptors prevented both LTD and LTP induction. In contrast, blocking dopamine D2 receptors delayed, but did not prevent, LTD and sped induction of LTP. We conclude (1) that, in combination with cortical inputs, single APs evoked in spiny projection neurons can induce both LTP and LTD of the corticostriatal pathway; (2) that the strength and direction of these synaptic changes depend deterministically on the AP timing relative to the arriving cortical inputs; (3) that, whereas dopamine D2 receptor activation modulates the initial phase of striatal STDP, dopamine D1/D5 receptor activation is critically required for striatal STDP. Thus, the timing of APs relative to cortical inputs alone is not enough to induce corticostriatal plasticity, implying that ongoing activity does not affect synaptic strength unless dopamine receptors are activated. 10.1523/JNEUROSCI.4402-07.2008

BOLD Responses Reflecting Dopaminergic Signals in the Human Ventral Tegmental Area

Kimberlee D'Ardenne — 2008-02-29T10:21:12-00:00

Science, Vol. 319, No. 5867. (29 February 2008), pp. 1264-1267.

Current theories hypothesize that dopamine neuronal firing encodes reward prediction errors. Although studies in nonhuman species provide direct support for this theory, functional magnetic resonance imaging (fMRI) studies in humans have focused on brain areas targeted by dopamine neurons [ventral striatum (VStr)] rather than on brainstem dopaminergic nuclei [ventral tegmental area (VTA) and substantia nigra]. We used fMRI tailored to directly image the brainstem. When primary rewards were used in an experiment, the VTA blood oxygen leveldependent (BOLD) response reflected a positive reward prediction error, whereas the VStr encoded positive and negative reward prediction errors. When monetary gains and losses were used, VTA BOLD responses reflected positive reward prediction errors modulated by the probability of winning. We detected no significant VTA BOLD response to nonrewarding events. 10.1126/science.1150605

Transgenic Inhibition of Synaptic Transmission Reveals Role of CA3 Output in Hippocampal Learning

Toshiaki Nakashiba — 2008-01-24T23:42:12-00:00

Science (24 January 2008), 1151120.

The hippocampus is an area of the brain involved in learning and memory. It contains parallel excitatory pathways referred to as the trisynaptic pathway (which carries information from the entorhinal cortex [->] dentate gyrus [->] CA3 [->] CA1 [->] entorhinal cortex) and the monosynaptic pathway (which connects entorhinal cortex [->] CA1 [->] entorhinal cortex). We developed a generally applicable tetanus toxin-based method for transgenic mice that permits inducible and reversible inhibition of synaptic transmission and applied it to the trisynaptic pathway while preserving transmission in the monosynaptic pathway. We found that synaptic output from CA3 in the trisynaptic pathway is dispensable and the short monosynaptic pathway is sufficient for incremental spatial learning. In contrast, the full trisynaptic pathway containing CA3 is required for rapid, one-trial contextual learning, for pattern completionbased memory recall and for spatial tuning of CA1 cells. 10.1126/science.1151120

The ventral striatum in off-line processing: ensemble reactivation during sleep and modulation by hippocampal ripples.

CM Pennartz — 2008-01-08T20:16:11-00:00

J Neurosci, Vol. 24, No. 29. (21 July 2004), pp. 6446-6456.

Previously it has been shown that the hippocampus and neocortex can spontaneously reactivate ensemble activity patterns during post-behavioral sleep and rest periods. Here we examined whether such reactivation also occurs in a subcortical structure, the ventral striatum, which receives a direct input from the hippocampal formation and has been implicated in guidance of consummatory and conditioned behaviors. During a reward-searching task on a T-maze, flanked by sleep and rest periods, parallel recordings were made from ventral striatal ensembles while EEG signals were derived from the hippocampus. Statistical measures indicated a significant amount of reactivation in the ventral striatum. In line with hippocampal data, reactivation was especially prominent during post-behavioral slow-wave sleep, but unlike the hippocampus, no decay in pattern recurrence was visible in the ventral striatum across the first 40 min of post-behavioral rest. We next studied the relationship between ensemble firing patterns in ventral striatum and hippocampal ripples-sharp waves, which have been implicated in pattern replay. Firing rates were significantly modulated in close temporal association with hippocampal ripples in 25% of the units, showing a marked transient enhancement in the average response profile. Strikingly, ripple-modulated neurons in ventral striatum showed a clear reactivation, whereas nonmodulated cells did not. These data suggest, first, the occurrence of pattern replay in a subcortical structure implied in the processing and prediction of reward and, second, a functional linkage between ventral striatal reactivation and a specific type of high-frequency population activity associated with hippocampal replay.

Putting a spin on the dorsal-ventral divide of the striatum.

P Voorn — 2006-01-25T02:36:21-00:00

Trends Neurosci, Vol. 27, No. 8. (August 2004), pp. 468-474.

Since its conception three decades ago, the idea that the striatum consists of a dorsal sensorimotor part and a ventral portion processing limbic information has sparked a quest for functional correlates and anatomical characteristics of the striatal divisions. But this classic dorsal-ventral distinction might not offer the best view of striatal function. Anatomy and neurophysiology show that the two striatal areas have the same basic structure and that sharp boundaries are absent. Behaviorally, a distinction between dorsolateral and ventromedial seems most valid, in accordance with a mediolateral functional zonation imposed on the striatum by its excitatory cortical, thalamic and amygdaloid inputs. Therefore, this review presents a synthesis between the dorsal-ventral distinction and the more mediolateral-oriented functional striatal gradient.

The tempotron: a neuron that learns spike timing–based decisions

Robert Gütig — 2006-02-24T04:26:03-00:00

Nature Neuroscience, Vol. 9, No. 3. (12 February 2006), pp. 420-428.

Rapid Neural Coding in the Retina with Relative Spike Latencies

Tim Gollisch — 2008-02-22T10:01:31-00:00

Science, Vol. 319, No. 5866. (22 February 2008), pp. 1108-1111.

Natural vision is a highly dynamic process. Frequent body, head, and eye movements constantly bring new images onto the retina for brief periods, challenging our understanding of the neural code for vision. We report that certain retinal ganglion cells encode the spatial structure of a briefly presented image in the relative timing of their first spikes. This code is found to be largely invariant to stimulus contrast and robust to noisy fluctuations in response latencies. Mechanistically, the observed response characteristics result from different kinetics in two retinal pathways ("ON" and "OFF") that converge onto ganglion cells. This mechanism allows the retina to rapidly and reliably transmit new spatial information with the very first spikes emitted by a neural population. 10.1126/science.1149639

Imaging in vivo: watching the brain in action.

Jason N D Kerr — 2008-02-20T11:14:34-00:00

Nat Rev Neurosci (13 February 2008)

The appeal of in vivo cellular imaging to any neuroscientist is not hard to understand: it is almost impossible to isolate individual neurons while keeping them and their complex interactions with surrounding tissue intact. These interactions lead to the complex network dynamics that underlie neural computation which, in turn, forms the basis of cognition, perception and consciousness. In vivo imaging allows the study of both form and function in reasonably intact preparations, often with subcellular spatial resolution, a time resolution of milliseconds and a purview of months. Recently, the limits of what can be achieved in vivo have been pushed into terrain that was previously only accessible in vitro, due to advances in both physical-imaging technology and the design of molecular contrast agents.

The hippocampus and memory: insights from spatial processing

Chris Bird — 2008-02-20T11:45:18-00:00

Nat Rev Neurosci, Vol. 9, No. 3. (March 2008), pp. 182-194.

Impaired Spatial Representation in CA1 after Lesion of Direct Input from Entorhinal Cortex

Vegard Brun — 2008-01-24T01:04:55-00:00

Neuron, Vol. 57, No. 2. (24 January 2008), pp. 290-302.

Summary Place-specific firing in the hippocampus is determined by path integration-based spatial representations in the grid-cell network of the medial entorhinal cortex. Output from this network is conveyed directly to CA1 of the hippocampus by projections from principal neurons in layer III, but also indirectly by axons from layer II to the dentate gyrus and CA3. The direct pathway is sufficient for spatial firing in CA1, but it is not known whether similar firing can also be supported by the input from CA3. To test this possibility, we made selective lesions in layer III of medial entorhinal cortex by local infusion of the neurotoxin [gamma]-acetylenic GABA. Firing fields in CA1 became larger and more dispersed after cell loss in layer III, whereas CA3 cells, which receive layer II input, still had sharp firing fields. Thus, the direct projection is necessary for precise spatial firing in the CA1 place cell population.

Neuronal representations of cognitive state: reward or attention?

John Maunsell — 2005-10-05T14:41:04-00:00

Trends in Cognitive Sciences, Vol. 8, No. 6. (1 June 2004), pp. 261-265.

The effects of spatial or featural attention on the activity of neurons have been studied in many experiments that have used a variety of neurophysiological approaches. Other experiments have examined how expectations about reward are represented in neuronal activity in various brain regions. Although attention and reward are distinct concepts, I argue here that many neurophysiological experiments on attention and reward do not permit a clean dissociation between the two. This problem arises in part because reward contingencies are the only parameter manipulated in any of these experiments. I describe how attention and reward expectations have been confounded, giving rise to uncertainty about how signals related to attention and reward are distributed in the brain.

In vitro and in vivo measures of evoked excitatory and inhibitory conductance dynamics in sensory cortices

C Monier — 2008-02-14T11:50:08-00:00

Journal of Neuroscience Methods, Vol. In Press, Corrected Proof

In order to better understand the synaptic nature of the integration process operated by cortical neurons during sensory processing, it is necessary to devise quantitative methods which allow one to infer the level of conductance change evoked by the sensory stimulation and, consequently, the dynamics of the balance between excitation and inhibition. Such detailed measurements are required to characterize the static versus dynamic nature of the non-linear interactions triggered at the single cell level by sensory stimulus. This paper primarily reviews experimental data from our laboratory based on direct conductance measurements during whole-cell patch clamp recordings in two experimental preparations: (1) in vitro, during electrical stimulation in the visual cortex of the rat and (2) in vivo, during visual stimulation, in the primary visual cortex of the anaesthetized cat. Both studies demonstrate that shunting inhibition is expressed as well in vivo as in vitro. Our in vivo data reveals that a high level of diversity is observed in the degree of interaction (from linear to non-linear) and in the temporal interplay (from push-pull to synchronous) between stimulus-driven excitation (E) and inhibition (I). A detailed analysis of the E/I balance during evoked spike activity further shows that the firing strength results from a simultaneous decrease of evoked inhibition and increase of excitation. Secondary, the paper overviews the various computational methods used in the literature to assess conductance dynamics, measured in current clamp as well as in voltage clamp in different neocortical areas and species, and discuss the consistency of their estimations.

Methods for whole-cell recording from visually preselected neurons of perirhinal cortex in brain slices from young and aging rats

James Moyer — 2008-02-12T10:42:09-00:00

Journal of Neuroscience Methods, Vol. 86, No. 1. (31 December 1998), pp. 35-54.

This manuscript describes methods for preparing, visualizing, and recording from healthy perirhinal cortex neurons in brain slices from young and aging rats. We focused on perirhinal cortex because of its role in learning, memory, and aging-related cognitive decline. Detailed accounts of our dissection procedures are reported. Procedures that reliably yielded healthy neurons from juvenile rats were not conducive to obtaining healthy, readily-patchable neurons from aging rats, suggesting a procedure-by-age interaction. Performing an intracardiac perfusion, using a temperature-controlled vibratome, matching osmolarity between the cutting and incubation saline, using a slow cutting speed, and incubating slices at a warm temperature for 30 min were important when working with older tissue. Excellent visualization of neurons at depths of up to 100 [mu]m was achieved in slices from all ages (without tissue clearing)--avoiding the need to record from surface neurons, which are more likely to have truncated processes. Whole-cell recordings typically remained stable for several hours in neurons prepared from rats at all ages. These procedures should benefit neuroscientists interested in applying visually-guided whole-cell patch-clamp techniques to brain slice experiments using aged tissue. These methods should also facilitate the application of fluorescent imaging technology to brain slices for studying aging-related changes.

An efficient algorithm for continuous time cross correlogram of spike trains

Il Park — 2008-02-11T10:52:51-00:00

Journal of Neuroscience Methods, Vol. 168, No. 2. (15 March 2008), pp. 514-523.

We propose an efficient algorithm to compute the smoothed correlogram for the detection of temporal relationship between two spike trains. Unlike the conventional histogram-based correlogram estimations, the proposed algorithm operates on continuous time and does not bin either the spike train nor the correlogram. Hence it can be more precise in detecting the effective delay between two recording sites. Moreover, it can take advantage of the higher temporal resolution of the spike times provided by the current recording methods. The Laplacian kernel for smoothing enables efficient computation of the algorithm. We also provide the basic statistics of the estimator and a guideline for choosing the kernel size. This new technique is demonstrated by estimating the effective delays in a neuronal network from synthetic data and recordings of dissociated cortical tissue.

Cocaine Seeking Habits Depend upon Dopamine-Dependent Serial Connectivity Linking the Ventral with the Dorsal Striatum

David Belin — 2008-02-11T10:34:40-00:00

Neuron, Vol. 57, No. 3. (7 February 2008), pp. 432-441.

Summary A neuroanatomical principle of striatal organization has been established through which ventral domains, including the nucleus accumbens, exert control over dorsal striatal processes mediated by so-called "spiraling," striato-nigro-striatal, circuitry. We have investigated the functional significance of this circuitry in the control over a cocaine-seeking habit by using an intrastriatal disconnection procedure that combined a selective, unilateral lesion of the nucleus accumbens core and infusion of a dopamine receptor antagonist into the contralateral dorsolateral striatum, thereby disrupting striato-midbrain-striatal serial connectivity bilaterally. We show that this disconnection selectively decreased drug-seeking behavior in rats extensively trained under a second-order schedule of cocaine reinforcement. These data thereby define the importance of interactions between ventral and dorsal domains of the striatum, mediated by dopaminergic transmission, in the neural mechanisms underlying the development and performance of cocaine-seeking habits that are a key characteristic of drug addiction.

Functional neuroanatomy of aversion and its anticipation.

JB Nitschke — 2008-02-04T12:31:32-00:00

Neuroimage, Vol. 29, No. 1. (1 January 2006), pp. 106-116.

The capacity to anticipate aversive circumstances is central not only to successful adaptation but also to understanding the abnormalities that contribute to excessive worry and anxiety disorders. Forecasting and reacting to aversive events mobilize a host of affective and cognitive capacities and corresponding brain processes. Rapid event-related functional magnetic resonance imaging (fMRI) in 21 healthy volunteers assessed the overlap and divergence in the neural instantiation of anticipating and being exposed to aversive pictures. Brain areas jointly activated by the anticipation of and exposure to aversive pictures included the dorsal amygdala, anterior insula, dorsal anterior cingulate cortex (ACC), right dorsolateral prefrontal cortex (DLPFC), and right posterior orbitofrontal cortex (OFC). Anticipatory processes were uniquely associated with activations in rostral ACC, a more superior sector of the right DLPFC, and more medial sectors of the bilateral OFC. Activation of the right DLPFC in anticipation of aversion was associated with self-reports of increased negative affect, whereas OFC activation was associated with increases in both positive and negative affect. These results show that anticipation of aversion recruits key brain regions that respond to aversion, thereby potentially enhancing adaptive responses to aversive events.