CiteULike: Tag neurobiology

Systematic analysis of genes required for synapse structure and function

Derek Sieburth — 2005-07-27T22:46:24-00:00

Nature, Vol. 436, No. 7050., pp. 510-517.

Domain-specificity and theory of mind: evaluating neuropsychological evidence

Ian Apperly — 2005-11-25T13:03:15-00:00

Trends in Cognitive Sciences, Vol. 9, No. 12. (December 2005), pp. 572-577.

Humans' unique aptitude for reasoning about mental states, known as Theory of Mind (ToM), can help explain the unique character of human communication and social interaction. ToM has been studied extensively in children, but there is no clear account of the cognitive basis of ToM in adults. Evidence from functional imaging and neuropsychology is beginning to address this surprising gap in our understanding, and this evidence is often thought to favour a domain-specific or modular architecture for ToM. We present a systematic approach to this issue for the paradigmatic case of belief reasoning, and argue that neuropsychological data provide no clear evidence for domain-specificity or modularity. Progress in understanding ToM requires new tasks that isolate potentially distinct components of this complex ability.

Drug addiction. Part II. Neurobiology of addiction.

J Vetulani — 2006-03-25T21:29:34-00:00

Pol J Pharmacol, Vol. 53, No. 4. (g 2001), pp. 303-317.

The drug addiction may be regarded as the disease of the brain reward system. This system, closely related to the system of emotional arousal, is located predominantly in the limbic structures of the brain. Its existence was proved by demonstration of the "pleasure centers," that were discovered as location from which electrical self-stimulation is readily evoked. The main neurotransmitter involved in the reward is dopamine, but other monoamines and acetylcholine may also participate. The anatomical core of the reward system are dopaminergic neurons of the ventral tegmentum that project to the nucleus accumbens, amygdala, prefrontal cortex and other forebrain structures. Several of those structures may be specifically involved in the reward produced by different substances, when anticipating the reward. The recent discovery of CART peptides may importantly expand our knowledge about the neurochemistry of reward. Natural rewarding activities and artificial chemical rewarding stimuli act at the same locations, but while natural activities are controlled by feedback mechanisms that activate aversive centers, no such restrictions bind the responses to artificial stimuli. There are several groups of substances that activate the reward system and they may produce addiction, which in humans is a chronic, recurrent disease, characterized by absolute dominance of drug-seeking behavior. The craving induced by substances of addiction inhibits other behaviors. The adaptation of an organism to a chronic intake of drugs involves development of adaptive changes, sensitization or tolerance. It is thought that the gap between sensitization developing for the incentive value of the drug and tolerance to the reward induced by its consumption underlies the vicious circle of events leading to drug dependence. The vulnerability to addiction is dependent not only on the environment, but also on genetic factors.

Neurobiology of addiction and implications for treatment.

A Lingford-Hughes — 2006-03-25T21:25:58-00:00

Br J Psychiatry, Vol. 182 (February 2003), pp. 97-100.

Evidence for Differential Cortical Input to Direct Pathway versus Indirect Pathway Striatal Projection Neurons in Rats

Wanlong Lei — 2006-09-28T07:58:32-00:00

J. Neurosci., Vol. 24, No. 38. (22 September 2004), pp. 8289-8299.

The two main types of corticostriatal neurons are those that project only intratelencephalically (IT-type), the intrastriatal terminals of which are 0.41 microm in mean diameter, and those that send their main axon into pyramidal tract and have a collateral projection to striatum (PT-type), the intrastriatal terminals of which are 0.82 microm in mean diameter. We used three approaches to examine whether the two striatal projection neuron types (striatonigral direct pathway vs striatopallidal indirect pathway) differ in their input from IT-type and PT-type neurons. First, we retrogradely labeled one striatal projection neuron type or the other with biotinylated dextran amine (BDA)-3000 molecular weight. We found that terminals making asymmetric axospinous contact with striatonigral neurons were 0.43 microm in mean diameter, whereas those making asymmetric axospinous contact with striatopallidal neurons were 0.69 microm. Second, we preferentially immunolabeled striatonigral neurons for D1 dopamine receptors or striatopallidal neurons for D2 dopamine receptors and found that axospinous terminals had a smaller mean size (0.45 microm) on D1+ spines than on D2+ spines (0.61 microm). Finally, we combined selective BDA labeling of IT-type or PT-type terminals with immunolabeling for D1 or D2, and found that IT-type terminals were twice as common as PT-type on D1+ spines, whereas PT-type terminals were four times as common as IT-type on D2+ spines. These various results suggest that striatonigral neurons preferentially receive input from IT-type cortical neurons, whereas striatopallidal neurons receive greater input from PT-type cortical neurons. This differential cortical connectivity may further the roles of the direct and indirect pathways in promoting desired movements and suppressing unwanted movements, respectively. 10.1523/JNEUROSCI.1990-04.2004

Spiking Interest in Computational Modeling: A Unified Approach to Cognitive Neuroscience. Review of Computational Explorations in Cognitive Neuroscience: Understanding the Mind by Simulating the Brain, by O'Reilly, R. C., & Munakata, Y.

Richard Golden — 2006-01-08T17:58:48-00:00

Journal of Mathematical Psychology, Vol. 46, No. 5. (October 2002), pp. 636-653.

Randall C. O'Reilly is an assistant professor in the Department of Psychology and Institute of Cognitive Science at the University of Colorado at Boulder. In 1996, he received his Ph.D. in psychology from Carnegie Mellon University under the supervision of Professor James L. McClelland. From 1996 to 1997, Randall O'Reilly was awarded a McDonnell-Pew Cognitive Neuroscience Postdoctoral Fellowship to study at the Department of Brain and Cognitive Sciences at the Massachusetts Institute of Technology. He has served on several National Institutes of Health grant peer review panels and is currently an associate editor of the journal Cognitive Science. Professor O'Reilly's primary research interests are concerned with understanding the biological basis of cognitive processes through a variety of methodologies including computational and formal models of the biological bases of cognition.Yuko Munakata is an associate professor in the Department of Psychology at the University of Denver. In 1996, she received her Ph.D. in psychology from Carnegie Mellon University under the supervision of Professor James L. McClelland. Professor Munakata is a panel member of the NIH Biobehavioral and Behavioral Processes Study Section, a recent recipient of the Boyd R. McCandless Young Scientist Award (American Psychological Association), and Co-Editor (with M. Johnson and R. O. Gilmore) of the book Brain Development and Cognition: A Reader (2nd ed.). From 1996 to 1997, Yuko Munakata was awarded a McDonnell-Pew Cognitive Neuroscience Postdoctoral Fellowship to study at the Department of Brain and Cognitive Sciences at the Massachusetts Institute of Technology. Professor Munakata's primary research interests are concerned with the development and evaluation of neural network models and other representational systems for the purposes of understanding human cognitive development.Richard M. Golden is associate professor of psychology, cognitive science, and electrical engineering at the University of Texas at Dallas. Professor Golden is currently a member of the editorial boards of the journals Neural Networks, Neural Processing Letters, and the Journal of Mathematical Psychology, which focus upon computational and mathematical analyses of neurally inspired mathematical models. He is also a member of the Governing Board of the Society for Text and Discourse and the author of the book Mathematical Methods for Neural Network Analysis and Design. Professor Golden's primary research interests are concerned with the development and evaluation of formal models of higher level cognitive processes through a variety of methodologies from fields such as dynamical systems theory, optimization theory, statistical pattern recognition, and computational cognitive neuroscience.

A Computational Model of How the Basal Ganglia Produce Sequences

Gregory Berns — 2005-12-12T16:17:14-00:00

Journal of Cognitive Neuroscience, Vol. 10, No. 1. (1 January 1998), pp. 108-121.

We propose a systems-level computational model of the basal ganglia based closely on known anatomy and physiology. First, we assume that the thalamic targets, which relay ascending information to cortical action and planning areas, are tonically inhibited by the basal ganglia. Second, we assume that the output stage of the basal ganglia, the internal segment of the globus pallidus (GPi), selects a single action from several competing actions via lateral interactions. Third, we propose that a form of local working memory exists in the form of reciprocal connections between the external globus pallidus (GPe) and the subthalamic nucleus (STN). As a test of the model, the system was trained to learn a sequence of states that required the context of previous actions. The striatum, which was assumed to represent a conjunction of cortical states, directly selected the action in the GP during training. The STN-to-GP connection strengths were modified by an associative learning rule and came to encode the sequence after 20 to 40 iterations through the sequence. Subsequently, the system automatically reproduced the sequence when cued to the first action. The behavior of the model was found to be sensitive to the ratio of the striatal-nigral learning rate to the STN-GP learning rate. Additionally, the degree of striatal inhibition of the globus pallidus had a significant influence on both learning and the ability to select an action. Low learning rates, which would be hypothesized to reflect low levels of dopamine, as in Parkinson's disease, led to slow acquisition of contextual information. However, this could be partially offset by modeling a lesion of the globus pallidus that resulted in an increase in the gain of the STN units. The parameter sensitivity of the model is discussed within the framework of existing behavioral and lesion data.

Efficient computation and cue integration with noisy population codes.

S Deneve — 2005-02-08T23:09:14-00:00

Nat Neurosci, Vol. 4, No. 8. (August 2001), pp. 826-831.

The brain represents sensory and motor variables through the activity of large populations of neurons. It is not understood how the nervous system computes with these population codes, given that individual neurons are noisy and thus unreliable. We focus here on two general types of computation, function approximation and cue integration, as these are powerful enough to handle a range of tasks, including sensorimotor transformations, feature extraction in sensory systems and multisensory integration. We demonstrate that a particular class of neural networks, basis function networks with multidimensional attractors, can perform both types of computation optimally with noisy neurons. Moreover, neurons in the intermediate layers of our model show response properties similar to those observed in several multimodal cortical areas. Thus, basis function networks with multidimensional attractors may be used by the brain to compute efficiently with population codes.

Biometric analyses of vibrissal tactile discrimination in the rat

Ge Carvell — 2006-04-26T08:54:32-00:00

J. Neurosci., Vol. 10, No. 8. (1 August 1990), pp. 2638-2648.

Hold your horses: A dynamic computational role for the subthalamic nucleus in decision making.

Michael Frank — 2006-09-28T18:04:56-00:00

Neural Networks (29 August 2006)

The basal ganglia (BG) coordinate decision making processes by facilitating adaptive frontal motor commands while suppressing others. In previous work, neural network simulations accounted for response selection deficits associated with BG dopamine depletion in Parkinson's disease. Novel predictions from this model have been subsequently confirmed in Parkinson patients and in healthy participants under pharmacological challenge. Nevertheless, one clear limitation of that model is in its omission of the subthalamic nucleus (STN), a key BG structure that participates in both motor and cognitive processes. The present model incorporates the STN and shows that by modulating when a response is executed, the STN reduces premature responding and therefore has substantial effects on which response is ultimately selected, particularly when there are multiple competing responses. Increased cortical response conflict leads to dynamic adjustments in response thresholds via cortico-subthalamic-pallidal pathways. The model accurately captures the dynamics of activity in various BG areas during response selection. Simulated dopamine depletion results in emergent oscillatory activity in BG structures, which has been linked with Parkinson's tremor. Finally, the model accounts for the beneficial effects of STN lesions on these oscillations, but suggests that this benefit may come at the expense of impaired decision making.

Intensification of cataleptic response in 6-hydroxydopamine-induced neurodegeneration of substantia nigra is not dependent on the degree of dopamine depletion.

J Srinivasan — 2006-10-02T10:00:59-00:00

Synapse, Vol. 51, No. 3. (1 March 2004), pp. 213-218.

An intensification of catalepsy has been observed upon repeated testing in rats with permanent neurodegeneration of substantia nigra. Here, the question is addressed whether the rate of development of intensification of catalepsy upon repeated testing in the same context is dependent on dopamine level in the basal ganglia. Rats were lesioned with 2 microg or 6 microg of 6-hydroxydopamine in the median forebrain bundle to produce dopamine depletion in substantia nigra in two different proportions. Both groups were exposed to catalepsy tests for 7 successive days in the same context, and the context was changed on day 8. On day 9 the catalepsy test was repeated with the old context. After the completion of the behavioral experiments, various regions of basal ganglia were analyzed for dopamine and its metabolites 3,4-dihydroxyphenylacetic acid, 3-methyl tyronine, and homovanillic acid. Lesions with 6 microg of 6-hydroxydopamine produced strong dopamine depletion (78%) and akinetic response in the catalepsy test on day 1. Repeated exposure of this group to the catalepsy tests in the same context produced intensification of cataleptic response. Changing the context on day 8 reduced catalepsy. Performing the experiments again with the old context on day 9 produced an intensified response. Lesions with 2 microg of 6-hydroxydopamine produced partial dopamine depletion (46%) without any motor disturbances. However, repeated exposure and context changes produced a similar pattern of catalepsy as in the 6 microg lesioned animals. These results indicate that the rate of building up of intensification of catalepsy is not dependent on the degree of dopamine depletion. It signifies the importance of context in the expression and augmentation of parkinsonian symptoms during the course of the disease to subjects with subthreshold dopaminergic neurodegeneration that could not produce motor disturbances alone. Prevention of context-dependent intensification of catalepsy could be beneficial in the treatment of Parkinson's disease.

Behavioural pharmacology of glutamate receptors in the basal ganglia.

WJ Schmidt — 2006-10-02T09:57:23-00:00

Neurosci Biobehav Rev, Vol. 21, No. 4. (July 1997), pp. 381-392.

Glutamate receptors play a major role in the transmitter balance within the basal ganglia (BG). N-methyl-D-aspartate (NMDA) receptor stimulation within the striatum acts behaviourally depressant while intrastriatal as well as systemic administration of NMDA receptor-antagonists have rather stimulatory effects despite the different profiles of non-competitive-, competitive NMDA receptor- and glycine site-antagonists. In animal models of Parkinson's disease all these NMDA receptor antagonists counteract parkinsonian symptoms or act synergistically with L-3,4-dihydroxyphenylalanine (L-DOPA). The strong locomotion-inducing effect of the non-competitive NMDA receptor antagonists is partly, but not fully, mediated by a dopamine (DA) release in the nucleus accumbens. Manipulations at alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptors produce poor behavioural effects. These, however, are different or even opposed to NMDA receptor mediated effects. Local infusions of AMPA receptor-antagonists into the BG output nuclei have an anti-parkinsonian effect but systemic injections are ineffective. These drugs even counteract the anti-parkinsonian effect of DA agonists and of non-competitive NMDA receptor antagonists as well as the DA releasing effects of the latter drugs. Only few data on the role of metabotropic receptors exist but the different receptor subtypes with different regional distribution represent a promising target for pharmacological interventions.

NMDA receptor antagonists do not block the development of sensitization of catalepsy, but make its expression state-dependent.

A Lanis — 2006-10-02T09:52:09-00:00

Behav Pharmacol, Vol. 12, No. 2. (April 2001), pp. 143-149.

Dopamine (DA) receptor blockade induces catalepsy in rats which increases in strength upon retesting. This increase in catalepsy represents a form of sensitization which has been shown to be completely context dependent. Sensitization of catalepsy therefore represents a good model for studying the neurobiological mechanisms underlying the interaction between the cellular effect of a drug (DA-receptor blockade) and the context. This study investigated whether glutamatergic mechanisms are involved in the development of sensitization. Rats were treated with either haloperidol or haloperidol plus an N-methyl-D-aspartate (NMDA) receptor antagonist. Haloperidol consistently induced catalepsy which developed sensitization upon retesting. Co-administration of D-CPPene (5 mg/kg and 10 mg/kg, i.p.), eliprodil (30 mg/kg, i.p.) or Ro 25-6981 (15 mg/kg, i.p.) did not have any effect on sensitization, although all three drugs exerted some anticataleptic effects. When sensitization developed under haloperidol plus NMDA receptor antagonist, the sensitized response was expressed only in the presence of the NMDA receptor antagonist. This strongly suggests that the NMDA receptor antagonists represent contextual stimuli to which catalepsy has been conditioned, and this implies that the expression of sensitization has been rendered state-dependent.

Intrastriatal injection of DL-2-amino-5-phosphonovaleric acid (AP-5) induces sniffing stereotypy that is antagonized by haloperidol and clozapine.

WJ Schmidt — 2006-10-02T09:47:18-00:00

Psychopharmacology (Berl), Vol. 90, No. 1. (1986), pp. 123-130.

DL-2-amino-5-phosphonovaleric acid (AP-5), which blocks glutamatergic transmission at the NMDA-preferring receptor, was injected into the antero-dorsal striatum of rats. AP-5-induced behavioural changes were assessed i) using a stereotypy rating scale and ii) using an experimental chamber designed to quantify sniffing. In both behavioural situations it was shown that AP-5 (10 micrograms/0.5 microliter) induced continuous intensive sniffing similar to that induced by small doses of systemically administered amphetamine or apomorphine. However, oral stereotypies were not induced by AP-5. Systemically injected clozapine (5 and 10 mg/kg SC) as well as haloperidol (0.1 mg/kg IP) antagonized AP-5-induced sniffing. These results show that besides dopamine receptors, NMDA receptors are involved in the control of sniffing. In behavioural terms, the effect of glutamate mediated by the NMDA receptor in the striatum is opposite to that of dopamine.

Computer modeling methods for neurons

Michael Hines — 2006-01-10T14:46:57-00:00

(1998), pp. 226-230.

A somatotopic map of vibrissa motion direction within a barrel column

Mark Andermann — 2006-03-27T16:11:32-00:00

Nature Neuroscience, Vol. 9, No. 4. (19 March 2006), pp. 543-551.

Neural Correlates of Vibrissa Resonance: Band-Pass and Somatotopic Representation of High-Frequency Stimuli

Mark Andermann — 2006-04-24T12:41:59-00:00

Neuron, Vol. 42, No. 3. (13 May 2004), pp. 451-463.

The array of vibrissae on a rat's face is the first stage of a high-resolution tactile sensing system. Recently, it was discovered that vibrissae (whiskers) resonate when stimulated at specific frequencies, generating several-fold increases in motion amplitude. We investigated the neural correlates of vibrissa resonance in trigeminal ganglion and primary somatosensory cortex (SI) neurons (regular and fast spiking units) by presenting low-amplitude, high-frequency vibrissa stimulation. We found that somatosensory neurons showed band-pass tuning and enhanced sensitivity to small amplitude stimuli, reflecting the resonance amplification of vibrissa motion. Further, a putative somatotopic map of frequency selectivity was observed in SI, with isofrequency columns extending along the representations of arcs of vibrissae, in agreement with the gradient in vibrissa resonance across the vibrissa pad. These findings suggest several parallels between frequency processing in the vibrissa system and the auditory system and have important implications for detection and discrimination of tactile information.

Frequency-Dependent Processing in the Vibrissa Sensory System

Christopher Moore — 2006-04-24T12:38:27-00:00

J Neurophysiol, Vol. 91, No. 6. (1 June 2004), pp. 2390-2399.

The vibrissa sensory system is a key model for investigating principles of sensory processing. Specific frequency ranges of vibrissa motion, generated by rodent sensory behaviors (e.g., active exploration or resting) and by stimulus features, characterize perception by this system. During active exploration, rats typically sweep their vibrissae at [~]4-12 Hz against and over tactual surfaces, and during rest or quiescence, their vibrissae are typically still (<1 Hz). When a vibrissa is swept over an object, microgeometric surface features (e.g., grains on sandpaper) likely create higher frequency vibrissa vibrations that are greater than or equal to several hundred Hertz. In this article, I first review thalamic and cortical neural responses to vibrissa stimulation at 1-40 Hz. I then propose that neural dynamics optimize the detection of stimuli in low-frequency contexts (e.g., 1 Hz) and the discrimination of stimuli in the whisking frequency range. In the third section, I describe how the intrinsic biomechanical properties of vibrissae, their ability to resonate when stimulated at specific frequencies, may promote detection and discrimination of high-frequency inputs, including textured surfaces. In the final section, I hypothesize that distinct low- and high-frequency processing modes may exist in the somatosensory cortex (SI), such that neural responses to stimuli at 1-40 Hz do not necessarily predict responses to higher frequency inputs. In total, these studies show that several frequency-specific mechanisms impact information transmission in the vibrissa sensory system and suggest that these properties play a crucial role in perception. 10.1152/jn.00925.2003

Dynamic Dopamine Modulation in the Basal Ganglia: A Neurocomputational Account of Cognitive Deficits in Medicated and Nonmedicated Parkinsonism

Michael Frank — 2006-01-05T13:43:21-00:00

J. Cogn. Neurosci., Vol. 17, No. 1. (1 January 2005), pp. 51-72.

Dopamine (DA) depletion in the basal ganglia (BG) of Parkinson's patients gives rise to both frontal-like and implicit learning impairments. Dopaminergic medication alleviates some cognitive deficits but impairs those that depend on intact areas of the BG, apparently due to DA "overdose." These findings are difficult to accommodate with verbal theories of BG/DA function, owing to complexity of system dynamics: DA dynamically modulates function in the BG, which is itself a modulatory system. This article presents a neural network model that instantiates key biological properties and provides insight into the underlying role of DA in the BG during learning and execution of cognitive tasks. Specifically, the BG modulates the execution of "actions" (e.g., motor responses and working memory updating) being considered in different parts of the frontal cortex. Phasic changes in DA, which occur during error feedback, dynamically modulate the BG threshold for facilitating/suppressing a cortical command in response to particular stimuli. Reduced dynamic range of DA explains Parkinson and DA overdose deficits with a single underlying dysfunction, despite overall differences in raw DA levels. Simulated Parkinsonism and medication effects provide a theoretical basis for behavioral data in probabilistic classification and reversal tasks. The model also provides novel testable predictions for neuropsychological and pharmacological studies, and motivates further investigation of BG/DA interactions with the prefrontal cortex in working memory.

Context-dependent catalepsy intensification is due to classical conditioning and sensitization.

J Amtage — 2006-06-14T16:20:13-00:00

Behav Pharmacol, Vol. 14, No. 7. (November 2003), pp. 563-567.

Haloperidol-induced catalepsy represents a model of neuroleptic-induced Parkinsonism. Daily administration of haloperidol, followed by testing for catalepsy on a bar and grid, results in a day-to-day increase in catalepsy that is completely context dependent, resulting in a strong placebo effect and in a failure of expression after a change in context. The aim of this study was to analyse the associative learning process that underlies context dependency. Catalepsy intensification was induced by a daily threshold dose of 0.25 mg/kg haloperidol. Extinction training and retesting under haloperidol revealed that sensitization was composed of two components: a context-conditioning component, which can be extinguished, and a context-dependent sensitization component, which cannot be extinguished. Context dependency of catalepsy thus follows precisely the same rules as context dependency of psychostimulant-induced sensitization. Catalepsy sensitization is therefore due to conditioning and sensitization.

Evolutionary, neurobiological, gene-based solution of the ideological "puzzle" of human altruism and cooperation.

R Baschetti — 2007-09-26T11:55:10-00:00

Med Hypotheses, Vol. 69, No. 2. (2007), pp. 241-249.

Despite hundreds of published articles about humankind's eusocial behaviours, most scholars still regard the origin of human altruism and cooperation as an enduring puzzle, because it seems incompatible with two central tenets of evolution, namely, the competition between individuals and the consequent selective advantages of selfish traits. This "puzzle", however, rather than being due to insurmountable scientific difficulties, is to be attributed to two powerful ideologies, which are politically opposite, but nevertheless concurred to prevent scholars from solving it. One ideology rejects the concept of genetic determinism, whereas the other dislikes the concept of group selection. As a consequence, these widespread ideologies, which are common in the scientific community, too, kept scholars from realising that the puzzle of human altruism and cooperation can only be solved by proposing a theoretical model that is based precisely on both genetic determinism and group selection. This model, which was never advanced in published papers, is presented here. This article also proposes to regard ancestral environments as determinants of human eusociality. By contrast, virtually all previous articles about it leave primitive habitats unmentioned. To support the hypothesis that human unselfish behaviours represent genetically conserved traits that evolved ancestrally, not products of cultural transmission, this paper also discusses six groups of arguments in the section "Genes versus culture". Finally, this article advances a purely genetic evolutionary explanation for the uniqueness of human eusociality, thereby challenging prevailing cultural explanations for the incomparably developed levels of cooperation in humankind, which are observed in no other social species.

A neurobiological model of visual attention and invariant pattern recognition based on dynamic routing of information

BA Olshausen — 2008-04-08T07:58:51-00:00

J. Neurosci., Vol. 13, No. 11. (1 November 1993), pp. 4700-4719.

Deoxyglucose analysis of retinotopic organization in primate striate cortex

Rb Tootell — 2007-02-10T01:20:15-00:00

Science, Vol. 218, No. 4575. (26 November 1982), pp. 902-904.

We have anatomically analyzed retinotopic organization using the 14C-labeled 2-deoxy-D-glucose method. The method has several advantages over conventional electrophysiological mapping techniques. In the striate cortex, the anatomical substrate for retinotopic organization is surprisingly well ordered, and there seems to be a systematic relationship between ocular dominance strips and cortical magnification. The 2-deoxyglucose maps in this area appear to be largely uninfluenced by known differences in long-term metabolic activity. This method should prove useful in analyzing retinotopic organization in various visual areas of the brain and in different species. 10.1126/science.7134981

Receptive fields and trigger features of ganglion cells in the visual streak of the rabbits retina.

WR Levick — 2008-07-25T23:28:16-00:00

The Journal of physiology, Vol. 188, No. 3. (February 1967), pp. 285-307.

1. A survey of the properties of retinal ganglion cells in the central part of the rabbit retina has been carried out.2. The five types of unit previously encountered in the peripheral retina were also found in the central region. Their receptive fields were smaller, and tended to be oval-shaped with the long axis horizontal.3. In addition, three new types were discovered: orientation-selective cells, local-edge-detectors, uniformity-detectors.4. Orientation-selective cells were sensitive to either vertically or horizontally extended targets. Analysis suggested they were modified concentric units with an incomplete antagonistic surround.5. Local-edge-detectors responded to the appearance or movement of a contrasting border within the receptive field. They were inhibited by similar stimulation of the region surrounding the receptive field. Detailed attention was given to the demonstration of edge-detection.6. Uniformity detectors had a relatively high level of ongoing activity in the absence of stimulation. All forms of stimulation (lights flashed on or off, movement of darker or lighter targets) produced a diminution or cessation of ongoing activity.7. The results are compared with behaviour described in other species.

Eye, Brain, and Vision (Scientific American Library)

David Hubel — 2008-07-19T23:44:47-00:00

Receptive fields and functional architecture of monkey striate cortex.

DH Hubel — 2006-08-13T19:45:22-00:00

J Physiol, Vol. 195, No. 1. (March 1968), pp. 215-243.

Thalamic relay functions and their role in corticocortical communication: generalizations from the visual system.

RW Guillery — 2008-08-04T08:51:52-00:00

Neuron, Vol. 33, No. 2. (17 January 2002), pp. 163-175.

All neocortical areas receive thalamic inputs. Some thalamocortical pathways relay information from ascending pathways (first order thalamic relays) and others relay information from other cortical areas (higher order thalamic relays), thus serving a role in corticocortical communication. Most, possibly all, afferents reaching thalamus, ascending and cortical, are branches of axons that innervate lower (motor) centers, so that thalamocortical pathways can be viewed generally as monitors of ongoing motor instructions. In terms of numbers, the thalamic relay is dominated by synapses that modulate the relay functions. One of the roles of these modulatory pathways is to change the transfer of information through the thalamus, in accord with current attentional demands. Other roles remain to be explored. These modulatory functions can be expected to act on corticocortical communication in addition to their action on ascending pathways.

How Close Are We to Understanding V1?

Bruno Olshausen — 2005-05-30T21:32:14-00:00

Neural Computation, Vol. 17, No. 8. (August 2005), pp. 1665-1699.

The Synaptic Organization of the Brain

2008-07-06T15:49:17-00:00

(06 November 2003)

It is widely recognized that the neural basis of brain function can be fully understood only by integrating many disciplines at many levels. Studies of synaptic organization are bringing about a quiet revolution in achieving this goal, as documented by this unique book over the past 30 years. In this fifth edition, the results of the mouse and human genome projects are incorporated for the first time. Molecular biologists interested in functional genomics and proteomics of the brain will find answers here to the critical questions: what are the cell and circuit functions of gene products? Also for the first time, the reader is oriented to supporting neuroscience databases. Among the new advances covered are 2-photon confocal laser microscopy of dendrites and dendritic spines, biochemical analyses, and dual patch and multielectrode recordings, applied together with an increasing range of behavioral and gene- targeting methods. Leading experts in the best understood brain regions bring together the molecular, anatomical, functional, and behavioral data in authoritative integrated accounts. The chapters are organized in the same format, covering the neural elements, synaptic connections, basic circuits, physiology, neurotransmitters, neuromodulators, membrane properties, dendritic properties, and with a final section on how the circuits mediate specific behaviors. The uniform framework for each chapter enables the authors to higlight the principles that are common to all regions, as well as the adaptations unique to each, thus serving as a model for understanding the neural basis of behavior.

The unsolved mystery of vision

Richard Masland — 2008-06-10T22:36:15-00:00

Current Biology, Vol. 17, No. 15. (7 August 2007), pp. R577-R582.

Vision looms large in neuroscience -- it is the subject of a gigantic literature and four Nobel prizes -- but there is a growing realization that there are problems with the textbook explanation of how mammalian vision works. Here we will summarize the evidence behind this disquiet. In effect, we shall present a portrait of a field that is [`]stuck'. Our initial focus, because it is our area of expertise, is on evidence that the early steps of mammalian vision are more diverse and more interesting than is usually imagined, so that our understanding of the later stages is in trouble right from the start. But we will also summarize problems, raised by others, with the later stages themselves.

The neural code of the retina.

M Meister — 2005-09-14T15:29:22-00:00

Neuron, Vol. 22, No. 3. (March 1999), pp. 435-450.

The receptive fields of cat retinal ganglion cells in physiological and pathological states: where we are after half a century of research.

JB Troy — 2008-07-25T12:49:00-00:00

Progress in retinal and eye research, Vol. 21, No. 3. (May 2002), pp. 263-302.

Studies on the receptive field properties of cat retinal ganglion cells over the past half-century are reviewed within the context of the role played by the receptive field in visual information processing. Emphasis is placed on the work conducted within the past 20 years, but a summary of key contributions from the 1950s to 1970s is provided. We have sought to review aspects of the ganglion cell receptive field that have not been featured prominently in previous review articles. Our review of the receptive field properties of X- and Y-cells focuses on quantitative studies and includes consideration of the function of the receptive field in visual signal processing. We discuss the non-classical as well as the classical receptive field. Attention is also given to the receptive field properties of the less well-studied cat ganglion cells-the W-cells-and the effect of pathology on cat ganglion cell properties. Although work from our laboratories is highlighted, we hope that we have given a reasonably balanced view of the current state of the field.

The fundamental plan of the retina

Richard Masland — 2007-09-07T14:50:57-00:00

Nat Neurosci, Vol. 4, No. 9. (2001), pp. 877-886.

Neurobiology: Feeling right about doing right

Deborah Talmi — 2007-04-18T22:42:07-00:00

Nature, Vol. 446, No. 7138. (18 April 2007), pp. 865-866.

Genes and the Environment in Neurodegeneration

Coppede — 2007-01-12T22:05:06-00:00

Bioscience Reports, Vol. 26, No. 5. (October 2006), pp. 341-367.

The neurobiology of positive emotions

Jeffrey Burgdorf — 2005-08-19T12:57:24-00:00

Neuroscience & Biobehavioral Reviews, Vol. In Press, Corrected Proof

Compared to the study of negative emotions such as fear, the neurobiology of positive emotional processes and the associated positive affect (PA) states has only recently received scientific attention. Biological theories conceptualize PA as being related to (i) signals indicating that bodies are returning to equilibrium among those studying homeostasis, (ii) utility estimation among those favoring neuroeconomic views, and (iii) approach and other instinctual behaviors among those cultivating neuroethological perspectives. Indeed, there are probably several distinct forms of positive affect, but all are closely related to ancient sub-neocortical limbic brain regions we share with other mammals. There is now a convergence of evidence to suggest that various regions of the limbic system, including especially ventral striatal dopamine systems are implemented in an anticipatory (appetitive) positive affective state. Dopamine independent mechanisms utilizing opiate and GABA receptors in the ventral striatum, amygdala and orbital frontal cortex are important in elaborating consummatory PA (i.e. sensory pleasure) states, and various neuropeptides mediate homeostatic satisfactions.

Electrical activity in early neuronal development

Nicholas Spitzer — 2006-12-06T23:59:52-00:00

Nature, Vol. 444, No. 7120., pp. 707-712.

Choosing the greater of two goods: neural currencies for valuation and decision making

Leo Sugrue — 2005-04-29T23:08:04-00:00

Nature Reviews Neuroscience, Vol. 6, No. 5. (01 May 2005), pp. 363-375.

Memory systems of the brain: a brief history and current perspective.

LR Squire — 2007-04-16T23:39:55-00:00

Neurobiol Learn Mem, Vol. 82, No. 3. (November 2004), pp. 171-177.

The idea that memory is composed of distinct systems has a long history but became a topic of experimental inquiry only after the middle of the 20th century. Beginning about 1980, evidence from normal subjects, amnesic patients, and experimental animals converged on the view that a fundamental distinction could be drawn between a kind of memory that is accessible to conscious recollection and another kind that is not. Subsequent work shifted thinking beyond dichotomies to a view, grounded in biology, that memory is composed of multiple separate systems supported, for example, by the hippocampus and related structures, the amygdala, the neostriatum, and the cerebellum. This article traces the development of these ideas and provides a current perspective on how these brain systems operate to support behavior.

Brain substrates of infant-mother attachment: contributions of opioids, oxytocin, and norepinephrine.

EE Nelson — 2005-10-22T22:01:46-00:00

Neurosci Biobehav Rev, Vol. 22, No. 3. (May 1998), pp. 437-452.

The aim of this paper is to review recent work concerning the psychobiological substrates of social bonding, focusing on the literature attributed to opioids, oxytocin and norepinephrine in rats. Existing evidence and thinking about the biological foundations of attachment in young mammalian species and the neurobiology of several other affiliative behaviors including maternal behavior, sexual behavior and social memory is reviewed. We postulate the existence of social motivation circuitry which is common to all mammals and consistent across development. Oxytocin, vasopressin, endogenous opioids and catecholamines appear to participate in a wide variety of affiliative behaviors and are likely to be important components in this circuitry. It is proposed that these same neurochemical and neuroanatomical patterns will emerge as key substrates in the neurobiology of infant attachments to their caregivers.

Traumatic entrapment, appeasement and complex post-traumatic stress disorder: evolutionary perspectives of hostage reactions, domestic abuse and the Stockholm syndrome.

C Cantor — 2007-09-01T05:02:00-00:00

Aust N Z J Psychiatry, Vol. 41, No. 5. (May 2007), pp. 377-384.

Evolutionary theory and cross-species comparisons are explored to shed new insights into behavioural responses to traumatic entrapment, examining their relationships to the Stockholm syndrome (a specific response to traumatic entrapment) and complex post-traumatic stress disorder (PTSD). A selective literature review is undertaken examining responses to traumatic entrapment (including hostage, domestic abuse and similar situations) and the Stockholm syndrome, before examining mammalian, reptilian and other defensive responses to relevant threats. Chimpanzees, the closest relatives of humans, are closely examined from this perspective and commonalities in behavioural responses are highlighted. The neurobiological basis of defensive behaviours underlying PTSD is explored with reference to the triune brain model. Victims of protracted traumatic entrapment under certain circumstances may display the Stockholm syndrome, which involves paradoxically positive relationships with their oppressors that may persist beyond release. Similar responses are observed in many mammalian species, especially primates. Ethological concepts including dominance hierarchies, reverted escape, de-escalation and conditional reconciliation appear relevant and are illustrated. These phenomena are commonly encountered in victims of severe abuse and understanding these concepts may assist clinical management. Appeasement is the mammalian defence most relevant to the survival challenge presented by traumatic entrapment and appears to be the foundation of complex PTSD. Evolutionary perspectives have considerable potential to bridge and integrate neurobiology and the social sciences with respect to traumatic stress responses.

Hypothalamic-pituitary-adrenal axis, neuroendocrine factors and stress

Constantine Tsigos — 2004-12-09T19:48:35-00:00

Journal of Psychosomatic Research, Vol. 53, No. 4. (October 2002), pp. 865-871.

The stress system coordinates the adaptive responses of the organism to stressors of any kind.1 The main components of the stress system are the corticotropin-releasing hormone (CRH) and locus ceruleus-norepinephrine (LC/NE)-autonomic systems and their peripheral effectors, the pituitary-adrenal axis, and the limbs of the autonomic system. Activation of the stress system leads to behavioral and peripheral changes that improve the ability of the organism to adjust homeostasis and increase its chances for survival. The CRH and LC/NE systems stimulate arousal and attention, as well as the mesocorticolimbic dopaminergic system, which is involved in anticipatory and reward phenomena, and the hypothalamic [beta]-endorphin system, which suppresses pain sensation and, hence, increases analgesia. CRH inhibits appetite and activates thermogenesis via the catecholaminergic system. Also, reciprocal interactions exist between the amygdala and the hippocampus and the stress system, which stimulates these elements and is regulated by them. CRH plays an important role in inhibiting GnRH secretion during stress, while, via somatostatin, it also inhibits GH, TRH and TSH secretion, suppressing, thus, the reproductive, growth and thyroid functions. Interestingly, all three of these functions receive and depend on positive catecholaminergic input. The end-hormones of the hypothalamic-pituitary-adrenal (HPA) axis, glucocorticoids, on the other hand, have multiple roles. They simultaneously inhibit the CRH, LC/NE and [beta]-endorphin systems and stimulate the mesocorticolimbic dopaminergic system and the CRH peptidergic central nucleus of the amygdala. In addition, they directly inhibit pituitary gonadotropin, GH and TSH secretion, render the target tissues of sex steroids and growth factors resistant to these substances and suppress the 5' deiodinase, which converts the relatively inactive tetraiodothyronine (T4) to triiodothyronine (T3), contributing further to the suppression of reproductive, growth and thyroid functions. They also have direct as well as insulin-mediated effects on adipose tissue, ultimately promoting visceral adiposity, insulin resistance, dyslipidemia and hypertension (metabolic syndrome X) and direct effects on the bone, causing "low turnover" osteoporosis. Central CRH, via glucocorticoids and catecholamines, inhibits the inflammatory reaction, while directly secreted by peripheral nerves CRH stimulates local inflammation (immune CRH). CRH antagonists may be useful in human pathologic states, such as melancholic depression and chronic anxiety, associated with chronic hyperactivity of the stress system, along with predictable behavioral, neuroendocrine, metabolic and immune changes, based on the interrelations outlined above. Conversely, potentiators of CRH secretion/action may be useful to treat atypical depression, postpartum depression and the fibromyalgia/chronic fatigue syndromes, all characterized by low HPA axis and LC/NE activity, fatigue, depressive symptomatology, hyperalgesia and increased immune/inflammatory responses to stimuli.

Earlier Development of the Accumbens Relative to Orbitofrontal Cortex Might Underlie Risk-Taking Behavior in Adolescents

Adriana Galvan — 2007-01-29T20:53:46-00:00

J. Neurosci., Vol. 26, No. 25. (21 June 2006), pp. 6885-6892.

Adolescence has been characterized by risk-taking behaviors that can lead to fatal outcomes. This study examined the neurobiological development of neural systems implicated in reward-seeking behaviors. Thirty-seven participants (7-29 years of age) were scanned using event-related functional magnetic resonance imaging and a paradigm that parametrically manipulated reward values. The results show exaggerated accumbens activity, relative to prefrontal activity in adolescents, compared with children and adults, which appeared to be driven by different time courses of development for these regions. Accumbens activity in adolescents looked like that of adults in both extent of activity and sensitivity to reward values, although the magnitude of activity was exaggerated. In contrast, the extent of orbital frontal cortex activity in adolescents looked more like that of children than adults, with less focal patterns of activity. These findings suggest that maturing subcortical systems become disproportionately activated relative to later maturing top-down control systems, biasing the adolescent's action toward immediate over long-term gains. 10.1523/JNEUROSCI.1062-06.2006

The neurobiology of attachment.

TR Insel — 2005-10-25T06:21:06-00:00

Nat Rev Neurosci, Vol. 2, No. 2. (February 2001), pp. 129-136.

It is difficult to think of any behavioural process that is more intrinsically important to us than attachment. Feeding, sleeping and locomotion are all necessary for survival, but humans are, as Baruch Spinoza famously noted, "a social animal" and it is our social attachments that we live for. Over the past decade, studies in a range of vertebrates, including humans, have begun to address the neural basis of attachment at a molecular, cellular and systems level. This review describes some of the important insights from this work.

Neurobiology of Depression

Eric Nestler — 2007-06-15T13:22:13-00:00

Neuron, Vol. 34, No. 1. (28 March 2002), pp. 13-25.

Current treatments for depression are inadequate for many individuals, and progress in understanding the neurobiology of depression is slow. Several promising hypotheses of depression and antidepressant action have been formulated recently. These hypotheses are based largely on dysregulation of the hypothalamic-pituitary-adrenal axis and hippocampus and implicate corticotropin-releasing factor, glucocorticoids, brain-derived neurotrophic factor, and CREB. Recent work has looked beyond hippocampus to other brain areas that are also likely involved. For example, nucleus accumbens, amygdala, and certain hypothalamic nuclei are critical in regulating motivation, eating, sleeping, energy level, circadian rhythm, and responses to rewarding and aversive stimuli, which are all abnormal in depressed patients. A neurobiologic understanding of depression also requires identification of the genes that make individuals vulnerable or resistant to the syndrome. These advances will fundamentally improve the treatment and prevention of depression.

Psychobiological mechanisms of resilience and vulnerability: implications for successful adaptation to extreme stress.

DS Charney — 2005-05-04T08:47:11-00:00

Am J Psychiatry, Vol. 161, No. 2. (February 2004), pp. 195-216.

OBJECTIVE: Most research on the effects of severe psychological stress has focused on stress-related psychopathology. Here, the author develops psychobiological models of resilience to extreme stress. METHOD: An integrative model of resilience and vulnerability that encompasses the neurochemical response patterns to acute stress and the neural mechanisms mediating reward, fear conditioning and extinction, and social behavior is proposed. RESULTS: Eleven possible neurochemical, neuropeptide, and hormonal mediators of the psychobiological response to extreme stress were identified and related to resilience or vulnerability. The neural mechanisms of reward and motivation (hedonia, optimism, and learned helpfulness), fear responsiveness (effective behaviors despite fear), and adaptive social behavior (altruism, bonding, and teamwork) were found to be relevant to the character traits associated with resilience. CONCLUSIONS: The opportunity now exists to bring to bear the full power of advances in our understanding of the neurobiological basis of behavior to facilitate the discoveries needed to predict, prevent, and treat stress-related psychopathology.

The neurobiology of love.

S Zeki — 2007-08-20T04:02:45-00:00

FEBS Lett, Vol. 581, No. 14. (12 June 2007), pp. 2575-2579.

Romantic and maternal love are highly rewarding experiences. Both are linked to the perpetuation of the species and therefore have a closely linked biological function of crucial evolutionary importance. The newly developed ability to study the neural correlates of subjective mental states with brain imaging techniques has allowed neurobiologists to learn something about the neural bases of both romantic and maternal love. Both types of attachment activate regions specific to each, as well as overlapping regions in the brain's reward system that coincide with areas rich in oxytocin and vasopressin receptors. Both deactivate a common set of regions associated with negative emotions, social judgment and 'mentalizing' that is, the assessment of other people's intentions and emotions. Human attachment seems therefore to employ a push-pull mechanism that overcomes social distance by deactivating networks used for critical social assessment and negative emotions, while it bonds individuals through the involvement of the reward circuitry, explaining the power of love to motivate and exhilarate. Yet the biological study of love, and especially romantic love, must go beyond and look for biological insights that can be derived from studying the world literature of love, and thus bring the output of the humanities into its orbit.

Neurobiological Correlates of Social Conformity and Independence During Mental Rotation

Gregory Berns — 2006-08-30T16:22:27-00:00

Biological Psychiatry, Vol. 58, No. 3. (1 August 2005), pp. 245-253.

BackgroundWhen individual judgment conflicts with a group, the individual will often conform his judgment to that of the group. Conformity might arise at an executive level of decision making, or it might arise because the social setting alters the individual's perception of the world.MethodsWe used functional magnetic resonance imaging and a task of mental rotation in the context of peer pressure to investigate the neural basis of individualistic and conforming behavior in the face of wrong information.ResultsConformity was associated with functional changes in an occipital-parietal network, especially when the wrong information originated from other people. Independence was associated with increased amygdala and caudate activity, findings consistent with the assumptions of social norm theory about the behavioral saliency of standing alone.ConclusionsThese findings provide the first biological evidence for the involvement of perceptual and emotional processes during social conformity.

The neural systems that mediate human perceptual decision making

Hauke Heekeren — 2008-05-20T13:20:10-00:00

Nature Reviews Neuroscience, Vol. 9, No. 6. (09 May 2008), pp. 467-479.

Neural systems responding to degrees of uncertainty in human decision-making

M Hsu — 2006-01-16T11:14:30-00:00

Science, Vol. 310, No. 5754. (9 December 2005), pp. 1680-1683.

Much is known about how people make decisions under varying levels of probability (risk). Less is known about the neural basis of decision-making when probabilities are uncertain because of missing information (ambiguity). In decision theory, ambiguity about probabilities should not affect choices. Using functional brain imaging, we show that the level of ambiguity in choices correlates positively with activation in the amygdala and orbitofrontal cortex, and negatively with a striatal system. Moreover, striatal activity correlates positively with expected reward. Neurological subjects with orbitofrontal lesions were insensitive to the level of ambiguity and risk in behavioral choices. These data suggest a general neural circuit responding to degrees of uncertainty, contrary to decision theory.