Monkey Prefrontal Cortical Pyramidal and Putative Interneurons Exhibit Differential Patterns of Activity Between Prosaccade and Antisaccade Tasks

Previous studies have shown that prefrontal cortex (PFC) neurons carry task-related activity; however, it is largely unknown how this selectivity is implemented in PFC microcircuitry. Here, we exploited known differences in extracellular action potential waveforms, and antidromic identification, to classify PFC neurons as putative pyramidal or interneurons, and investigate their relative contributions to task-selectivity. We recorded the activity of prefrontal neurons while monkeys performed a blocked pro/antisaccade task in which they were required to look either toward or away from a peripheral visual stimulus. We found systematic differences in activity between neuron classes. Putative pyramidal neurons had higher stimulus-related activity on antisaccade trials, whereas putative interneurons exhibited greater activity for prosaccades. These findings suggest that task-selectivity in the PFC may be shaped by interactions between these neuronal classes. They are also consistent with the robust deficits in antisaccade performance frequently observed in disease states associated with PFC dysfunction.

[1]  J. Schall,et al.  Neural Control of Voluntary Movement Initiation , 1996, Science.

[2]  P S Goldman-Rakic,et al.  Functional synergism between putative gamma-aminobutyrate-containing neurons and pyramidal neurons in prefrontal cortex. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[3]  G. Leichnetz,et al.  The prefrontal corticotectal projection in the monkey; An anterograde and retrograde horseradish peroxidase study , 1981, Neuroscience.

[4]  David A Lewis,et al.  Functional properties of fast spiking interneurons and their synaptic connections with pyramidal cells in primate dorsolateral prefrontal cortex. , 2005, Journal of neurophysiology.

[5]  D. McCormick,et al.  Comparative electrophysiology of pyramidal and sparsely spiny stellate neurons of the neocortex. , 1985, Journal of neurophysiology.

[6]  E. Miller,et al.  Task-specific neural activity in the primate prefrontal cortex. , 2000, Journal of neurophysiology.

[7]  Mingsha Zhang,et al.  Neuronal switching of sensorimotor transformations for antisaccades , 2000, Nature.

[8]  Stefan Everling,et al.  Focused attention modulates visual responses in the primate prefrontal cortex. , 2004, Journal of neurophysiology.

[9]  S. Wise,et al.  Rule-dependent neuronal activity in the prefrontal cortex , 1999, Experimental Brain Research.

[10]  Earl K. Miller,et al.  Neurobiology: Straight from the top , 1999, Nature.

[11]  Madeleine Schlag-Rey,et al.  Primate antisaccade. II. Supplementary eye field neuronal activity predicts correct performance. , 2004, Journal of neurophysiology.

[12]  Jude F. Mitchell,et al.  Differential Attention-Dependent Response Modulation across Cell Classes in Macaque Visual Area V4 , 2007, Neuron.

[13]  N. P. Bichot,et al.  Perceptual and motor processing stages identified in the activity of macaque frontal eye field neurons during visual search. , 1996, Journal of neurophysiology.

[14]  Trevor J. Crawford,et al.  Parsing cognition in schizophrenia using saccadic eye movements: a selective overview , 2001, Neuropsychologia.

[15]  S P Wise,et al.  The role of ventral and orbital prefrontal cortex in conditional visuomotor learning and strategy use in rhesus monkeys (Macaca mulatta). , 2001, Behavioral neuroscience.

[16]  P. Goldman-Rakic,et al.  Correlated discharges among putative pyramidal neurons and interneurons in the primate prefrontal cortex. , 2002, Journal of neurophysiology.

[17]  Masaki Tanaka,et al.  Enhanced modulation of neuronal activity during antisaccades in the primate globus pallidus. , 2009, Cerebral cortex.

[18]  B. Bean.  The action potential in mammalian central neurons , 2007, Nature Reviews Neuroscience.

[19]  K. Johnston,et al.  Monkey Dorsolateral Prefrontal Cortex Sends Task-Selective Signals Directly to the Superior Colliculus , 2006, The Journal of Neuroscience.

[20]  D. Munoz,et al.  Look away: the anti-saccade task and the voluntary control of eye movement , 2004, Nature Reviews Neuroscience.

[21]  D. Lewis,et al.  Cortical inhibitory neurons and schizophrenia , 2005, Nature Reviews Neuroscience.

[22]  M. Goldberg,et al.  Activity of neurons in the lateral intraparietal area of the monkey during an antisaccade task , 1999, Nature Neuroscience.

[23]  Matthew F S Rushworth,et al.  Attentional Selection and Action Selection in the Ventral and Orbital Prefrontal Cortex , 2005, The Journal of Neuroscience.

[24]  H. Markram,et al.  Interneurons of the neocortical inhibitory system , 2004, Nature Reviews Neuroscience.

[25]  S. Hutton,et al.  The antisaccade task as a research tool in psychopathology: a critical review. , 2006, Psychophysiology.

[26]  J. Hartigan,et al.  The Dip Test of Unimodality , 1985 .

[27]  M. Schlag-Rey,et al.  Antisaccade performance predicted by neuronal activity in the supplementary eye field , 1997, Nature.

[28]  D P Munoz,et al.  Neuronal Correlates for Preparatory Set Associated with Pro-Saccades and Anti-Saccades in the Primate Frontal Eye Field , 2000, The Journal of Neuroscience.

[29]  K. Fukushima,et al.  Disturbances of voluntary control of saccadic eye movements in schizophrenic patients , 1988, Biological Psychiatry.

[30]  Stefan Everling,et al.  Task-relevant Output Signals are Sent from Monkey Dorsolateral Prefrontal Cortex to the Superior Colliculus during a Visuospatial Working Memory Task , 2009, Journal of Cognitive Neuroscience.

[31]  A. Nieder,et al.  Complementary Contributions of Prefrontal Neuron Classes in Abstract Numerical Categorization , 2008, The Journal of Neuroscience.

[32]  P. Goldman-Rakic,et al.  Synaptic mechanisms and network dynamics underlying spatial working memory in a cortical network model. , 2000, Cerebral cortex.

[33]  Hannah Monyer,et al.  Functional and Molecular Differences between Voltage-Gated K+ Channels of Fast-Spiking Interneurons and Pyramidal Neurons of Rat Hippocampus , 1998, The Journal of Neuroscience.

[34]  Y Agid,et al.  Cortical control of reflexive visually-guided saccades. , 1991, Brain : a journal of neurology.

[35]  A. Sillito,et al.  Modulatory and inhibitory processes in the visual cortex , 1985, Vision Research.

[36]  R. Douglas,et al.  Frontal lobe lesions in man cause difficulties in suppressing reflexive glances and in generating goal-directed saccades , 2004, Experimental Brain Research.

[37]  Amanda Parker,et al.  Memory after frontal/temporal disconnection in monkeys: conditional and non-conditional tasks, unilateral and bilateral frontal lesions , 1998, Neuropsychologia.

[38]  E. Miller,et al.  A Neural Circuit Model of Flexible Sensorimotor Mapping: Learning and Forgetting on Multiple Timescales , 2007, Neuron.

[39]  D. Simons.  Response properties of vibrissa units in rat SI somatosensory neocortex. , 1978, Journal of neurophysiology.

[40]  H. Spinnler.  The prefrontal cortex, Anatomy, physiology, and neuropsychology of the frontal lobe, J.M. Fuster. Raven Press, New York (1980), IX-222 pages , 1981 .

[41]  David A Lewis,et al.  Synaptic efficacy during repetitive activation of excitatory inputs in primate dorsolateral prefrontal cortex. , 2004, Cerebral cortex.

[42]  J. Duncan,et al.  Filtering of neural signals by focused attention in the monkey prefrontal cortex , 2002, Nature Neuroscience.

[43]  Stefan Everling,et al.  Rule-dependent Activity for Prosaccades and Antisaccades in the Primate Prefrontal Cortex , 2005, Journal of Cognitive Neuroscience.

[44]  E. Miller,et al.  An integrative theory of prefrontal cortex function. , 2001, Annual review of neuroscience.

[45]  S. Everling,et al.  The antisaccade: a review of basic research and clinical studies , 1998, Neuropsychologia.

[46]  P. Goldman-Rakic,et al.  Isodirectional tuning of adjacent interneurons and pyramidal cells during working memory: evidence for microcolumnar organization in PFC. , 1999, Journal of neurophysiology.

[47]  Michele A. Basso,et al.  The tell-tale tasks: A review of saccadic research in psychiatric patient populations , 2008, Brain and Cognition.

[48]  Earl K. Miller,et al.  Selective representation of relevant information by neurons in the primate prefrontal cortex , 1998, Nature.

[49]  P. E. Hallett,et al.  Primary and secondary saccades to goals defined by instructions , 1978, Vision Research.

[50]  M Gur,et al.  Physiological properties of macaque V1 neurons are correlated with extracellular spike amplitude, duration, and polarity. , 1999, Journal of neurophysiology.

[51]  K. C. Anderson,et al.  Single neurons in prefrontal cortex encode abstract rules , 2001, Nature.

[52]  K. Johnston,et al.  Top-Down Control-Signal Dynamics in Anterior Cingulate and Prefrontal Cortex Neurons following Task Switching , 2007, Neuron.

[53]  K. Johnston,et al.  Microstimulation of monkey dorsolateral prefrontal cortex impairs antisaccade performance , 2008, Experimental Brain Research.

[54]  D. Munoz,et al.  Reflex suppression in the anti-saccade task is dependent on prestimulus neural processes. , 1998, Journal of neurophysiology.

[55]  P. Goldman-Rakic,et al.  Prefrontal neuronal activity in rhesus monkeys performing a delayed anti-saccade task , 1993, Nature.

[56]  S. Anderson,et al.  The origin and specification of cortical interneurons , 2006, Nature Reviews Neuroscience.

[57]  Maria V. Sanchez-Vives,et al.  Electrophysiological classes of cat primary visual cortical neurons in vivo as revealed by quantitative analyses. , 2003, Journal of neurophysiology.

[58]  Stefan Everling,et al.  Neural Activity in Monkey Prefrontal Cortex Is Modulated by Task Context and Behavioral Instruction during Delayed-match-to-sample and Conditional ProsaccadeAntisaccade Tasks , 2006, Journal of Cognitive Neuroscience.

[59]  J. Lipski,et al.  Antidromic activation of neurones as an analytic tool in the study of the central nervous system , 1981, Journal of Neuroscience Methods.

[60]  P. Goldman-Rakic,et al.  Division of labor among distinct subtypes of inhibitory neurons in a cortical microcircuit of working memory. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[61]  H. Niki,et al.  Encoding of behavioral significance of visual stimuli by primate prefrontal neurons: relation to relevant task conditions , 2004, Experimental Brain Research.

[62]  Thomas Naselaris,et al.  Dynamic Sculpting of Directional Tuning in the Primate Motor Cortex during Three-Dimensional Reaching , 2008, The Journal of Neuroscience.

[63]  Keiji Tanaka,et al.  Mnemonic Function of the Dorsolateral Prefrontal Cortex in Conflict-Induced Behavioral Adjustment , 2007, Science.

[64]  D P Munoz,et al.  Role of Primate Superior Colliculus in Preparation and Execution of Anti-Saccades and Pro-Saccades , 1999, The Journal of Neuroscience.

[65]  Marjorie Sorge.  STRAIGHT FROM THE TOP , 1998 .

[66]  B. Connors,et al.  Intrinsic firing patterns of diverse neocortical neurons , 1990, Trends in Neurosciences.

[67]  B J Richmond,et al.  Temporal encoding of two-dimensional patterns by single units in primate inferior temporal cortex. II. Quantification of response waveform. , 1987, Journal of neurophysiology.

[68]  P. Goldman-Rakic,et al.  Destruction and Creation of Spatial Tuning by Disinhibition: GABAA Blockade of Prefrontal Cortical Neurons Engaged by Working Memory , 2000, The Journal of Neuroscience.

[69]  J. Hyvärinen,et al.  Cortical neuronal mechanisms in flutter-vibration studied in unanesthetized monkeys. Neuronal periodicity and frequency discrimination. , 1969, Journal of neurophysiology.