The readings listed below, which include both review readings and articles from the primary literature, are the foundation of this course. Where available, journal article abstracts from PubMed (an online database providing access to citations from biomedial literature) are included.

Required Reading

Zigmond, Michael, ed. Fundamental Neuroscience. 1st ed. 1999.

Readings by Lecture

Lectures 2, 3, 4, and 5:

Textbook Chapters: 29, 33, 34, 35.


Bower, J. M. Prog. Brain Res 114 (1997): 463-496.

Graybiel. "The basal ganglia and chunking of action repertoires." Neurobiol Learn Mem 70 (1998): 119-136.

PubMed abstract: The basal ganglia have been shown to contribute to habit and stimulus-response (S-R) learning. These forms of learning have the property of slow acquisition and, in humans, can occur without conscious awareness. This paper proposes that one aspect of basal ganglia-based learning is the recoding of cortically derived information within the striatum. Modular corticostriatal projection patterns, demonstrated experimentally, are viewed as producing recoded templates suitable for the gradual selection of new input-output relations in cortico-basal ganglia loops. Recordings from striatal projection neurons and interneurons show that activity patterns in the striatum are modified gradually during the course of S-R learning. It is proposed that this recoding within the striatum can chunk the representations of motor and cognitive action sequences so that they can be implemented as performance units. This scheme generalizes Miller's notion of information chunking to action control. The formation and the efficient implementation of action chunks are viewed as being based on predictive signals. It is suggested that information chunking provides a mechanism for the acquisition and the expression of action repertoires that, without such information compression would be biologically unwieldy or difficult to implement. The learning and memory functions of the basal ganglia are thus seen as core features of the basal ganglia's influence on motor and cognitive pattern generators. Copyright 1998 Academic Press.

Hikosaka, et al. "Parallel neural networks for learning sequential procedures." TINS 22 (1999): 464-471.

PubMed abstract: Recent studies have shown that multiple brain areas contribute to different stages and aspects of procedural learning. On the basis of a series of studies using a sequence-learning task with trial-and-error, we propose a hypothetical scheme in which a sequential procedure is acquired independently by two cortical systems, one using spatial coordinates and the other using motor coordinates. They are active preferentially in the early and late stages of learning, respectively. Both of the two systems are supported by loop circuits formed with the basal ganglia and the cerebellum, the former for reward-based evaluation and the latter for processing of timing. The proposed neural architecture would operate in a flexible manner to acquire and execute multiple sequential procedures.

Rizzolatti, G., and G. Luppino. "The cortical motor system." Neuron 31 (2001): 889-901.

PubMed abstract: The cortical motor system of primates is formed by a mosaic of anatomically and functionally distinct areas. These areas are not only involved in motor functions, but also play a role in functions formerly attributed to higher order associative cortical areas. In the present review, we discuss three types of higher functions carried out by the motor cortical areas: sensory-motor transformations, action understanding, and decision processing regarding action execution. We submit that generating internal representations of actions is central to cortical motor function. External contingencies and motivational factors determine then whether these action representations are transformed into actual actions.

Tanji, J. "Sequential organization of multiple movements: involvement of cortical motor areas." Annu. Rev. Neurosci. 24 (2001): 631-651.

PubMed abstract: Much of our normal behavior depends on the sequential execution of multiphased movements, or the execution of multiple movements arranged in a correct temporal order. This article deals with the issue of motor selection to arrange multiple movements in an appropriate temporal order, rather than the issue of constructing spatio-temporal structures in a single action. Planning, generating, and controlling the sequential motor behavior involves multiple cortical and subcortical neural structures. Studies on human subjects and nonhuman primates, however, have revealed that the medial motor areas in the frontal cortex and the basal ganglia play particularly important roles in the temporal sequencing of multiple movements. Cellular activity observed in the supplementary and presupplementary motor areas while performing specifically designed motor tasks suggests the way in which these areas take part in constructing the time structure for the sequential execution of multiple movements

Thach, W. T., H. P. Goodkin, and J. T. Keating. "The cerebellum and the adaptive coordination of movement." Annu. Rev. Neurosci. 15 (1992): 403-442.

PubMed abstract: Based on a review of cerebellar anatomy, neural discharge in relation to behavior, and focal ablation syndromes, we propose a model of cerebellar function that we believe is both comprehensive as to the available information (at these levels) and unique in several respects. The unique features are the inclusion of new information on (a) cerebellar output--its replicative representation of body maps in each of the deep nuclei, each coding a different type and context of movement, and each appearing to control movement of multiple body parts more than of single body parts; and (b) the newly assessed long length of the parallel fiber. The parallel fiber, by virtue of its connection through Purkinje cells to the deep nuclei, appears optimally designed to combine the actions at several joints and to link the modes of adjacent nuclei into more complex coordinated acts. We review the old question of whether the cerebellum is responsible for the coordination of body parts as opposed to the tuning of downstream executive centers, and conclude that it is both, through mechanisms that have been described in the cerebellar cortex. We argue that such a mechanism would require an adaptive capacity, and support the evidence and interpretation that it has one. We point out that many parts of the motor system may be involved in different types of motor learning for different purposes, and that the presence of the many does not exclude an existence of the one in the cerebellar cortex. The adaptive role of the cerebellar cortex would appear to be specialized for combining simpler elements of movement into more complex synergies, and also in enabling simple, stereotyped reflex apparatus to respond differently, specifically, and appropriately under different task conditions. Speed of learning and magnitude of memory for both novel synergies and task-specific performance modifications are other attributes of the cerebellar cortex.

Discussion Articles:

Graziano, M. S. A., et al. "Complex movements evoked by microstimulation of precentral cortex." Neuron 34 (2002): 841-851.

PubMed abstract: Electrical microstimulation was used to study primary motor and premotor cortex in monkeys. Each stimulation train was 500 ms in duration, approximating the time scale of normal reaching and grasping movements and the time scale of the neuronal activity that normally accompanies movement. This stimulation on a behaviorally relevant time scale evoked coordinated, complex postures that involved many joints. For example, stimulation of one site caused the mouth to open and also caused the hand to shape into a grip posture and move to the mouth. Stimulation of this site always drove the joints toward this final posture, regardless of the direction of movement required to reach the posture. Stimulation of other cortical sites evoked different postures. Postures that involved the arm were arranged across cortex to form a map of hand positions around the body. This stimulation-evoked map encompassed both primary motor and the adjacent premotor cortex. We suggest that these regions fit together into a single map of the workspace around the body.

Imamizu, H., et al. "Human cerebellar activity reflecting an acquired internal model of a new tool." Nature 403 (2000): 192-195.

PubMed abstract: Theories of motor control postulate that the brain uses internal models of the body to control movements accurately. Internal models are neural representations of how, for instance, the arm would respond to a neural command, given its current position and velocity. Previous studies have shown that the cerebellar cortex can acquire internal models through motor learning. Because the human cerebellum is involved in higher cognitive function as well as in motor control, we propose a coherent computational theory in which the phylogenetically newer part of the cerebellum similarly acquires internal models of objects in the external world. While human subjects learned to use a new tool (a computer mouse with a novel rotational transformation), cerebellar activity was measured by functional magnetic resonance imaging. As predicted by our theory, two types of activity were observed. One was spread over wide areas of the cerebellum and was precisely proportional to the error signal that guides the acquisition of internal models during learning. The other was confined to the area near the posterior superior fissure and remained even after learning, when the error levels had been equalized, thus probably reflecting an acquired internal model of the new tool.

Krauzlis, R. J. "Commentary." Neuron 34 (2002): 673-674.

Lauwereyns, J., et al. "A neural correlate of response bias in monkey caudate nucleus." Nature 418 (2002): 413-417.

PubMed abstract: Primates are equipped with neural circuits in the prefrontal cortex, the parietal cortex and the basal ganglia that predict the availability of reward during the performance of behavioural tasks. It is not known, however, how reward value is incorporated in the control of action. Here we identify neurons in the monkey caudate nucleus that create a spatially selective response bias depending on the expected gain. In behavioural tasks, the monkey had to make a visually guided eye movement in every trial, but was rewarded for a correct response in only half of the trials. Reward availability was predictable on the basis of the spatial position of the visual target. We found that caudate neurons change their discharge rate systematically, even before the appearance of the visual target, and usually fire more when the contralateral position is associated with reward. Strong anticipatory activity of neurons with a contralateral preference is associated with decreased latency for eye movements in the contralateral direction. We conclude that this neuronal mechanism creates an advance bias that favours a spatial response when it is associated with a high reward value.

Wessberg, J., et al. "Real-time prediction of hand trajectory by ensembles of cortical neurons in primates." Nature 408 (2000): 361-365.

PubMed abstract: Signals derived from the rat motor cortex can be used for controlling one-dimensional movements of a robot arm. It remains unknown, however, whether real-time processing of cortical signals can be employed to reproduce, in a robotic device, the kind of complex arm movements used by primates to reach objects in space. Here we recorded the simultaneous activity of large populations of neurons, distributed in the premotor, primary motor and posterior parietal cortical areas, as non-human primates performed two distinct motor tasks. Accurate real-time predictions of one- and three-dimensional arm movement trajectories were obtained by applying both linear and nonlinear algorithms to cortical neuronal ensemble activity recorded from each animal. In addition, cortically derived signals were successfully used for real-time control of robotic devices, both locally and through the Internet. These results suggest that long-term control of complex prosthetic robot arm movements can be achieved by simple real-time transformations of neuronal population signals derived from multiple cortical areas in primates.

Lectures 7, 8, 9, 10, 11:

Textbook Chapters: 28, 36.


Schiller, P. H. "The neural control of visually guided eye movements." In Cognitive Neuroscience of Attention. Edited by J. E. Richards. Erlbaum Associates, 1998.

___. "The ON and OFF channels of the mammalian visual system." In Progress in Retinal and Eye Research. Vol. 15. Edited by N. N. Osborne, and G. J. Chader. Oxford, England: Pergamon Press, 1995.

Schiller, P. H., and N. K. Logothetis. "The color-opponent and broad-band channels of the primate visual system." Trends in Neurosciences 13 (1990): 392-398.

PubMed abstract: hysiological, anatomical and psychophysical studies have identified several parallel channels of information processing in the primate visual system. Two of these, the color-opponent and the broad-band channels, originate in the retina and remain in part segregated through several higher cortical stations. To improve understanding of their function, recent studies have examined the visual capacities of monkeys following selective disruption of these channels. Color vision, fine- but not coarse-form vision and stereopsis are severely impaired in the absence of the color-opponent channel, whereas motion and flicker perception are impaired at high but not low temporal frequencies in the absence of the broad-band channel. The results suggest that the color-opponent channel extends the range of vision in the spatial and wavelength domains, and that the broad-band channel extends it in the temporal domain. Lesion studies also indicate that these channels must reach higher cortical centers through extrastriate regions other than just area V4 and the middle temporal area, and that the analysis performed by these two regions cannot be uniquely identified with specific visual capacities.

Wassle, H., and B. B. Boycott. "Functional architecture of the mammalian retina." Physiological Rev. 71 (1991): 447-479.

Discussion Articles:

Dacey, D. M., B. B. Lee, D. K. Stafford, J. Pokorny, and V. C. Smith. "Horizontal cells of the primate retina: cone specificity without spectral opponency." Science 271 (1996): 656-9.

PubMed abstract: The chromatic dimensions of human color vision have a neural basis in the retina. Ganglion cells, the output neurons of the retina, exhibit spectral opponency; they are excited by some wavelengths and inhibited by others. The hypothesis that the opponent circuitry emerges from selective connections between horizontal cell interneurons and cone photoreceptors sensitive to long, middle, and short wavelengths (L-, M-, and S-cones) was tested by physiologically and anatomically characterizing cone connections of horizontal cell mosaics in macaque monkeys. H1 horizontal cells received input only from L- and M-cones, whereas H2 horizontal cells received a strong input from S-cones and a weaker input from L- and M-cones. All cone inputs were the same sign, and both horizontal cell types lacked opponency. Despite cone type selectivity, the horizontal cell cannot be the locus of an opponent transformation in primates, including humans.

Ferrera, V. P., T. A. Nealy, and J. H. R. Maunsell. "Mixed parvocellular and magnocellular geniculate signals in visual area v4." Nature 358 (1992): 756-758.

PubMed abstract: Visual information from the retina is transmitted to the cerebral cortex by way of the lateral geniculate nucleus (LGN) in the thalamus. In primates, most of the retinal ganglion cells that project to the LGN belong to one of two classes, P and M, whose axons terminate in the parvocellular or magnocellular subdivisions of the LGN. These cell classes give rise to two channels that have been distinguished anatomically, physiologically and behaviourally. The visual cortex also can be subdivided into two pathways, one specialized for motion processing and the other for colour and form information. Several lines of indirect evidence have suggested a close correspondence between the subcortical and cortical pathways, such that the M channel provides input to the motion pathway and the P channel drives the colour/form pathway. This hypothesis was tested directly by selectively inactivating either the magnocellular or parvocellular subdivision of the LGN and recording the effects on visual responses in the cortex. We have previously reported that, in accordance with the hypothesis, responses in the motion pathway in the cortex depend primarily on magnocellular LGN. We now report that in the colour/form pathway, visual responses depend on both P and M input. These results argue against a simple correspondence between the subcortical and cortical pathways.

Hikosaka, O., and R. H. Wurtz. "Modification of saccadic eye movements by GABA-related substances. I. Effect of muscimol and bicuculine in monkey superior colliculus." J. Neurophysiol 53 (1985): 266-291.

PubMed abstract: Our previous observations led to the hypothesis that cells in the substantia nigra pars reticulata (SNr) tonically inhibit saccade-related cells in the intermediate layers of the superior colliculus (SC). Before saccades to visual or remembered targets, cells in SNr briefly reduce that inhibition, allowing a burst of spikes of SC cells that, in turn, leads to the initiation of a saccadic eye movement. Since this inhibition is likely to be mediated by gamma-aminobutyric acid (GABA), we tested this hypothesis by injecting a GABA agonist (muscimol) or a GABA antagonist (bicuculline) into the superior colliculus and measured the effects on saccadic eye movements made to visual or remembered targets. An injection of muscimol selectively suppressed saccades to the movement field of the cells near the injection site. The affected area expanded over time, thus suggesting the diffusion of muscimol in the SC; the area never included the other hemifield, suggesting that the diffusion was limited to one SC. One of the monkeys became unable to make any saccades to the affected area. Saccades to visual targets following injection of muscimol had longer latency and slightly shorter amplitudes that were corrected by subsequent saccades. The most striking change was a decrease in the peak velocity of the saccade, frequently to less than half the preinjection value. Saccades to remembered targets following injection of muscimol also showed an increase in latency and decrease in velocity, but in addition, showed a striking decrease in the accuracy of the saccades. The trajectories of saccades became distorted as if they were deflected away from the affected area. After muscimol injection, the area over which spontaneous eye movements were made shifted toward the side ipsilateral to the injection. Saccades toward the contralateral side were less frequent and slower. In nystagmus, which developed later, the slow phase was toward the contralateral side. In contrast to muscimol, injection of bicuculline facilitated the initiation of saccades. Injection was followed almost immediately by stereotyped and apparently irrepressible saccades made toward the center of the movement field of the SC cells at the injection site. The monkeys became unable to fixate during the tasks; the fixation was interrupted by saccadic jerks made to the affected area of the visual field and then back to the fixation point.

___. "Modification of saccadic eye movements by GABA-related substances. II. Effect of muscimol in monkey substantia nigra pars reticulata." J. Neurophysiol 53 (1985): 292-307.

PubMed abstract: The preceding study (21) showed that a gamma-aminobutyric acid (GABA) agonist or antagonist injected into the superior colliculus (SC) disrupted saccadic eye movements. The purpose of the present experiments was to determine whether this result was due to altering the inhibitory input to the SC from the substantia nigra pars reticulata (SNr). SNr cells are themselves inhibited by GABA. Injection of muscimol, a GABA agonist, into the SNr should increase the inhibition acting on SNr cells and should reduce the inhibition acting on the SC. If the effects of GABA inhibition in the SC results from terminals originating in the SNr, muscimol in the SNr should act like bicuculline in the SC. Muscimol in the SNr has the same general effect as bicuculline in the SC. The monkey made irrepressible saccades toward the contralateral visual field where cells in the SNr at the injection site had their visual or movement field. During visual fixation saccadic jerks occurred, interspersed with spontaneous saccades, instead of saccades to visual targets or to remembered targets. Saccades to remembered targets were more vulnerable to these saccadic intrusions than were saccades to visual targets. Since muscimol in the SNr acts like bicuculline in the SC, we conclude that a substantial fraction of GABA-mediated inhibitory inputs in the SC originates from the SNr. These experiments, in conjunction with previous experiments, show that the SNr exerts a tonic inhibition on saccade-related cells in SC and that this inhibition is mediated by GABA. The role of the SNr in initiation of saccades to remembered targets is particularly important since these saccades are more severely disrupted by muscimol in the SNr as well as in the SC. We suggest that both of these conclusions about eye movement might apply to skeletal movements as well. First, the basal ganglia contribute to the initiation of movement by a release of the target structure from tonic inhibition. Second, this mechanism is particularly critical of the movements based on stored or remembered signals that are not currently available as incoming sensory inputs.

Maunsell, J. H. R., T. A. Nealy, and D. D. DePriest. "Magnocellular and parovcellular contributions to responses in the middle temporal area (MT) of the macaque monkey." J. Neurosci. 10 (1990): 3323-3334.

PubMed abstract: Many lines of evidence suggest that the visual signals relayed through the magnocellular and parvocellular subdivisions of the primate dorsal LGN remain largely segregated through several levels of cortical processing. It has been suggested that this segregation persists through to the highest stages of the visual cortex, and that the pronounced differences between the neuronal response properties in the parietal cortex and inferotemporal cortex may be attributed to differential contributions from magnocellular and parvocellular signals. We have examined this hypothesis directly by recording the responses of cortical neurons while selectively blocking responses in the magnocellular or parvocellular layers of the LGN. Responses were recorded from single units or multiunit clusters in the middle temporal visual area (MT), which is part of the pathway leading to parietal cortex and thought to receive primarily magnocellular inputs. Responses in the MT were consistently reduced when the magnocellular subdivision of the LGN was inactivated. The reduction was almost always pronounced and often complete. In contrast, parvocellular block rarely produced striking changes in MT responses and typically had very little effect. Nevertheless, unequivocal parvocellular contributions could be demonstrated for a minority of MT responses. At a few MT sites, responses were recorded while magnocellular and parvocellular blocks were made simultaneously. Responses were essentially eliminated for all these paired blocks. These results provide direct evidence for segregation of magnocellular and parvocellular contributions in the extrastriate visual cortex and support the suggestion that these signals remain largely segregated through the highest levels of cortical processing.

Oyster, C. W., and H. B. Barlow. "Direction-selective units in rabbit retina: Distribution of preferred directions." Science 155 (1967): 841-842.

Additional Background:

Schiller, P. H. "The central visual system." Vision Res. 26 (1986): 1351-1386.

___. "Past and present ideas about how the visual scene is analyzed by the brain." Cerebral Cortex 12. Edited by Extrastriate Cortex, Kaas, and Rockland. Plenum Press (1997).

Sekuler, R., and R. Blake. Chap. 5, 6, 7, and 8 in Perception. 3rd ed. McGraw-Hill, 1995. This is for students with no background in vision.


Textbook Chapters: 23, 27.


Brown, M. C. "Functional neuroanatomy of the cochlea." In Physiology of the Ear. Edited by A. F. Jahn, and J. Santos-Sacchi. New York: Raven Press, 2001, pp. 529-548.

Hudspeth, A. J. "Hearing." Chap. 30 in Principles of Neural Science. Edited by E. R. Kandel, J. H. Schwartz, and T. M. Jessell. New York: McGraw-Hill, 2000, pp. 590-613.

___. "Sensory Transduction in the Ear." Chap. 31 in Principles of Neural Science. Edited by E. R. Kandel, J. H. Schwartz, and T. M. Jessell. 4th ed. New York: McGraw-Hill, pp. 614-624.

Discussion Articles:

Brand, A., O. Behrend, T. Marquardt, D. McAlpine, and B. Grothe. "Precise inhibition is essential for microsecond interaural time difference coding." Nature 417 (2002): 543-547.

Kanold, P. O., and E. D. Young. "Proprioceptive information from the pinna provides somatosensory input to cat dorsal cochlear nucleus." J. Neurosci. 21 (2001): 7848-7858.

PubMed abstract: The dorsal cochlear nucleus (DCN) is a second-order auditory structure that also receives nonauditory information, including somatosensory inputs from the dorsal column and spinal trigeminal nuclei. Here we investigate the peripheral sources of the somatosensory inputs to DCN. Electrical stimulation was applied to cervical nerves C1-C8, branches of C2, branches of the trigeminal nerve, and hindlimb nerves. The largest evoked potentials in the DCN were produced by C2 stimulation and by stimulation of its branches that innervate the pinna. Electrical stimulation of C2 produced a pattern of inhibition and excitation of DCN principal cells comparable with that seen in previous studies with stimulation of the primary somatosensory nuclei, suggesting that the same pathway was activated. Because C2 contains both proprioceptive and cutaneous fibers, we applied peripheral somatosensory stimulation to identify the effective somatosensory modalities. Only stimuli that activate pinna muscle receptors, such as stretch or vibration of the muscles connected to the pinna, were effective in driving DCN units, whereas cutaneous stimuli such as light touch, brushing of hairs, and stretching of skin were ineffective. These results suggest that the largest somatosensory inputs to the DCN originate from muscle receptors associated with the pinna. They support the hypothesis that a role of the DCN in hearing is to coordinate pinna orientation to sounds or to support correction for the effects of pinna orientation on sound-localization cues.

Liberman, M. C., et al. "Prestin is required for electromotility of the outer hair cell and for the cochlear amplifier." Nature 419 (2002): 300-304.

May, B. J. and S. J. McQuone. "Effects of bilateral olivocochlear lesions on pure-tone intensity discrimination in cats." Auditory Neurosci. 1 (1995): 385-400.

Portfors, C. V., and J. J. Wenstrup. "Delay-tuned neurons in the inferior colliculus of the mustached bat: Implications for analyses of target distance." J. Neurophysiol 82 (1999): 1326-1338.

PubMed abstract: We examined response properties of delay-tuned neurons in the central nucleus of the inferior colliculus (ICC) of the mustached bat. In the mustached bat, delay-tuned neurons respond best to the combination of the first-harmonic, frequency-modulated (FM1) sweep in the emitted pulse and a higher harmonic frequency-modulated (FM2, FM3 or FM4) component in returning echoes and are referred to as FM-FM neurons. We also examined H1-CF2 neurons. H1-CF2 neurons responded to simultaneous presentation of the first harmonic (H1) in the emitted pulse and the second constant frequency (CF2) component in returning echoes. These neurons served as a comparison as they are thought to encode different features of sonar targets than FM-FM neurons. Only 7% of our neurons (14/198) displayed a single excitatory tuning curve. The rest of the neurons (184) displayed complex responses to sounds in two separate frequency bands. The majority (51%, 101) of neurons were facilitated by the combination of specific components in the mustached bat's vocalizations. Twenty-five percent showed purely inhibitory interactions. The remaining neurons responded to two separate frequencies, without any facilitation or inhibition. FM-FM neurons (69) were facilitated by the FM1 component in the simulated pulse and a higher harmonic FM component in simulated echoes, provided the high-frequency signal was delayed the appropriate amount. The delay producing maximal facilitation ("best delay") among FM-FM neurons ranged between 0 and 20 ms, corresponding to target distances </=3.4 m. Sharpness of delay tuning varied among FM-FM neurons with 50% delay widths between 2 and 13 ms. On average, the facilitated responses of FM-FM neurons were 104% greater than the sum of the responses to the two signals alone. In comparing response properties of delay-tuned, FM-FM neurons in the ICC with those in the medial geniculate body (MGB) from other studies, we find that the range of best delays, sharpness of delay tuning and strength of facilitation are similar in the ICC and MGB. This suggests that by the level of the IC, the basic response properties of FM-FM neurons are established, and they do not undergo extensive transformations with ascending auditory processing.


Textbook Chapters: 46, 53, 55, 56.


Luscher, C., R. A. Nicoll, R. C. Malenka, and D. Muller. "Synaptic plasticity and dynamic modulation of the postsynaptic membrane." Nature Neuroscience 5 (2000): 545-550.

PubMed abstract: The biochemical composition of the postsynaptic membrane and the structure of dendritic spines may be rapidly modulated by synaptic activity. Here we review these findings, discuss their implications for long-term potentiation (LTP) and long-term depression (LTD) and propose a model of sequentially occurring expression mechanisms.

Moser, E. I., and O. Paulsen. "New excitement in cognitive space: between place cells and spatial memory." Current Opinion in Neurobiology 11 (2001): 745-751.

PubMed abstract: Hippocampal principal neurons-'place cells'-exhibit location-specific firing. Recent work addresses the link between place cell activity and hippocampal memory function. New tasks that challenge spatial memory allow recording from single neurons, as well as ensembles of neurons, during memory computations, and insights into the cellular mechanisms of spatial memory are beginning to emerge.

Discussion Articles

Frank, L. M., E. N. Brown, and M. Wilson. "Trajectory encoding in the hippocampus and entorhinal cortex." Neuron 27 (2000): 169-178

PubMed abstract: We recorded from single neurons in the hippocampus and entorhinal cortex (EC) of rats to investigate the role of these structures in navigation and memory representation. Our results revealed two novel phenomena: first, many cells in CA1 and the EC fired at significantly different rates when the animal was in the same position depending on where the animal had come from or where it was going. Second, cells in deep layers of the EC, the targets of hippocampal outputs, appeared to represent the similarities between locations on spatially distinct trajectories through the environment. Our findings suggest that the hippocampus represents the animal's position in the context of a trajectory through space and that the EC represents regularities across different trajectories that could allow for generalization across experiences.

Louie, K., and M. A. Wilson. "Temporally structured replay of awake hippocampal ensemble activity during rapid eye movement sleep." Neuron 29 (2001): 145-156.

PubMed abstract: Human dreaming occurs during rapid eye movement (REM) sleep. To investigate the structure of neural activity during REM sleep, we simultaneously recorded the activity of multiple neurons in the rat hippocampus during both sleep and awake behavior. We show that temporally sequenced ensemble firing rate patterns reflecting tens of seconds to minutes of behavioral experience are reproduced during REM episodes at an equivalent timescale. Furthermore, within such REM episodes behavior-dependent modulation of the subcortically driven theta rhythm is also reproduced. These results demonstrate that long temporal sequences of patterned multineuronal activity suggestive of episodic memory traces are reactivated during REM sleep. Such reactivation may be important for memory processing and provides a basis for the electrophysiological examination of the content of dream states.

Nakazawa, K., et al. "Requirement for hippocampal CA3 NMDA receptors in associative memory recall." Science 297 (2002): 211-218.

PubMed abstract: Pattern completion, the ability to retrieve complete memories on the basis of incomplete sets of cues, is a crucial function of biological memory systems. The extensive recurrent connectivity of the CA3 area of hippocampus has led to suggestions that it might provide this function. We have tested this hypothesis by generating and analyzing a genetically engineered mouse strain in which the N-methyl-D-asparate (NMDA) receptor gene is ablated specifically in the CA3 pyramidal cells of adult mice. The mutant mice normally acquired and retrieved spatial reference memory in the Morris water maze, but they were impaired in retrieving this memory when presented with a fraction of the original cues. Similarly, hippocampal CA1 pyramidal cells in mutant mice displayed normal place-related activity in a full-cue environment but showed a reduction in activity upon partial cue removal. These results provide direct evidence for CA3 NMDA receptor involvement in associative memory recall.

Shi, S-H., Y. Hayashi, J. A. Esteban, and R. Malinow. "Subunit-specific rules governing AMPA-receptor trafficking to synapses in hippocampal pyramidal neurons." Cell 105 (2001): 331-343.

PubMed abstract: Synaptic transmission in the brain. In hippocampus, most AMPA-Rs are hetero-oligomers composed of GluR1/GluR2 or GluR2/GluR3 subunits. Here we show that these AMPA-R forms display different synaptic delivery mechanisms. GluR1/GluR2 receptors are added to synapses during plasticity; this requires interactions between GluR1 and group I PDZ domain proteins. In contrast, GluR2/GluR3 receptors replace existing synaptic receptors continuously; this occurs only at synapses that already have AMPA-Rs and requires interactions by GluR2 with NSF and group II PDZ domain proteins. The combination of regulated addition and continuous replacement of synaptic receptors can stabilize long-term changes in synaptic efficacy and may serve as a general model for how surface receptor number is established and maintained.


Textbook Chapters: 53*, 54, 59 (*different from Wilson 53)


Fuster, J. M. "Executive frontal functions." Exp. Brain Res. 133, 1 (Jul 2000): 66-70.

PubMed abstract: This chapter presents a conceptual model of the representational and executive functions of the cortex of the frontal lobe derived from empirical evidence obtained principally in the monkey. According to this model, the neuronal networks of the frontal lobe that represent motor or executive memories are probably the same networks that cooperate with other cerebral structures in the temporal organization of behavior. The prefrontal cortex, at the top of the perception-action cycle, plays a critical role in the mediation of contingencies of action across time, an essential aspect of the temporal organization of behavior. That role of cross-temporal mediation is based on the interplay of two short-term cognitive functions: one retrospective, of short-term memory or sensory working memory, and the other prospective, of attentive set (or motor working memory). Both appear represented in the neuronal populations of dorsolateral prefrontal cortex. At least one of the mechanisms for the retention of working memory of either kind seems to be the reentry of excitability through recurrent cortical circuits. With those two complementary and temporally symmetrical cognitive functions of active memory for the sensory past and for the motor future, the prefrontal cortex secures the temporal closure at the top of the perception-action cycle.

Miller, E. K., and J. D. Cohen. "An integrative theory of prefrontal cortex function." Annual Review of Neuroscience 24 (2001): 167-202.

PubMed abstract: The prefrontal cortex has long been suspected to play an important role in cognitive control, in the ability to orchestrate thought and action in accordance with internal goals. Its neural basis, however, has remained a mystery. Here, we propose that cognitive control stems from the active maintenance of patterns of activity in the prefrontal cortex that represent goals and the means to achieve them. They provide bias signals to other brain structures whose net effect is to guide the flow of activity along neural pathways that establish the proper mappings between inputs, internal states, and outputs needed to perform a given task. We review neurophysiological, neurobiological, neuroimaging, and computational studies that support this theory and discuss its implications as well as further issues to be addressed.

Discussion Articles:

Bichot, N. P., and J. D. Schall. "Effects of similarity and history on neural mechanisms of visual selection." Nat. Neurosci. 2, 6 (Jun): 549-54.

PubMed abstract: To investigate how the brain combines knowledge with visual processing to locate eye movement targets, we trained monkeys to search for a target defined by a conjunction of color and shape. On successful trials, neurons in the frontal eye field not only discriminated the target from distractors, but also discriminated distractors that shared a target feature as well as distractors that had been the search target during the previous session. Likewise, occasional errant saccades tended to direct gaze to distractors that either resembled the current target or had been the previous target. These findings show that the frontal eye field is involved in visual and not just motor selection and that visual selection is influenced by long-term priming. The data support the hypothesis that visual selection can be accomplished by parallel processing of objects based on their elementary features.

Everling, S., C. J. Tinsley, D. Gaffan, and J. Duncan. "Filtering of neural signals by focused attention in the monkey prefrontal cortex." Nat. Neurosci. 5, 7 (Jul 2002): 671-6.

PubMed abstract: Prefrontal cortex is thought to be important in attention and awareness. Here we recorded the activity of prefrontal neurons in monkeys carrying out a focused attention task. Having directed attention to one location, monkeys monitored a stream of visual objects, awaiting a predefined target. Although neurons rarely discriminated between one non-target and another, they commonly discriminated between targets and non-targets. From the onset of the visual response, this target/non-target discrimination was effectively eliminated when the same objects appeared at an unattended location in the opposite visual hemifield. The results show that, in prefrontal cortex, filtering of ignored locations is strong, early and spatially global. Such filtering may be important in blindness to unattended signals--a conspicuous aspect of human selective attention.

Tomita, H., M. Ohbayashi, K. Nakahara, I. Hasegawa, and Y. Miyashita. "Top-down signal from prefrontal cortex in executive control of memory retrieval." Nature 401, 6754 (14 Oct 1999): 699-703.

PubMed abstract: Knowledge or experience is voluntarily recalled from memory by reactivation of the neural representations in the cerebral association cortex. In inferior temporal cortex, which serves as the storehouse of visual long-term memory, activation of mnemonic engrams through electric stimulation results in imagery recall in humans, and neurons can be dynamically activated by the necessity for memory recall in monkeys. Neuropsychological studies and previous split-brain experiments predicted that prefrontal cortex exerts executive control upon inferior temporal cortex in memory retrieval; however, no neuronal correlate of this process has ever been detected. Here we show evidence of the top-down signal from prefrontal cortex. In the absence of bottom-up visual inputs, single inferior temporal neurons were activated by the top-down signal, which conveyed information on semantic categorization imposed by visual stimulus-stimulus association. Behavioural performance was severely impaired with loss of the top-down signal. Control experiments confirmed that the signal was transmitted not through a subcortical but through a fronto-temporal cortical pathway. Thus, feedback projections from prefrontal cortex to the posterior association cortex appear to serve the executive control of voluntary recall.

Tremblay, L., S. N. Gettner, and C. R. Olson. "Neurons with object-centered spatial selectivity in macaque SEF: do they represent locations or rules?" J. Neurophysiol 87 (2002): 330-550.

PubMed abstract: In macaque monkeys performing a task that requires eye movements to the leftmost or rightmost of two dots in a horizontal array, some neurons in the supplementary eye field (SEF) fire differentially according to which side of the array is the target regardless of the array's location on the screen. We refer to these neurons as exhibiting selectivity for object-centered location. This form of selectivity might arise from involvement of the neurons in either of two processes: representing the locations of targets or representing the rules by which targets are selected. To distinguish between these possibilities, we monitored neuronal activity in the SEF of two monkeys performing a task that required the selection of targets by either an object-centered spatial rule or a color rule. On each trial, a sample array consisting of two side-by-side dots appeared; then a cue flashed on one dot; then the display vanished and a delay ensued. Next a target array consisting of two side-by-side dots appeared at an unpredictable location and another delay ensued; finally the monkey had to make an eye movement to one of the target dots. On some trials, the monkey had to select the dot on the same side as the cue (right or left). On other trials, he had to select the target of the same color as the cue (red or green). Neuronal activity robustly encoded the object-centered locations first of the cue and then of the target regardless of the whether the monkey was following a rule based on object-centered location or color. Neuronal activity was at most weakly affected by the type of rule the monkey was following (object-centered-location or color) or by the color of the cue and target (red or green). On trials involving a color rule, neuronal activity was moderately enhanced when the cue and target appeared on opposite sides of their respective arrays. We conclude that the general function of SEF neurons selective for object-centered location is to represent where the cue and target are in their respective arrays rather than to represent the rule for target selection.

Wallis, J. D., K. C. Anderson, and E. K. Miller. "Single neurons in the prefrontal cortex encode abstract rules." Nature 411 (2001): 953-956.

PubMed abstract: The ability to abstract principles or rules from direct experience allows behaviour to extend beyond specific circumstances to general situations. For example, we learn the 'rules' for restaurant dining from specific experiences and can then apply them in new restaurants. The use of such rules is thought to depend on the prefrontal cortex (PFC) because its damage often results in difficulty in following rules. Here we explore its neural basis by recording from single neurons in the PFC of monkeys trained to use two abstract rules. They were required to indicate whether two successively presented pictures were the same or different depending on which rule was currently in effect. The monkeys performed this task with new pictures, thus showing that they had learned two general principles that could be applied to stimuli that they had not yet experienced. The most prevalent neuronal activity observed in the PFC reflected the coding of these abstract rules.