Electrophysiological classes of layer 2/3 pyramidal cells in monkey prefrontal cortex.

The activity of supragranular pyramidal neurons in the dorsolateral prefrontal cortex (DLPFC) neurons is hypothesized to be a key contributor to the cellular basis of working memory in primates. Therefore, the intrinsic membrane properties, a crucial determinant of a neuron's functional properties, are important for the role of DLPFC pyramidal neurons in working memory. The present study aimed to investigate the biophysical properties of pyramidal cells in layer 2/3 of monkey DLPFC to create an unbiased electrophysiological classification of these cells. Whole cell voltage recordings in the slice preparation were performed in 77 pyramidal cells, and 24 electrophysiological measures of their passive and active intrinsic membrane properties were analyzed. Based on the results of cluster analysis of 16 independent electrophysiological variables, 4 distinct electrophysiological classes of monkey pyramidal cells were determined. Two classes contain regular-spiking neurons with low and high excitability and constitute 52% of the pyramidal cells sampled. These subclasses of regular-spiking neurons mostly differ in their input resistance, minimum current that evoked firing, and current-to-frequency transduction properties. A third class of pyramidal cells includes low-threshold spiking cells (17%), which fire a burst of three-five spikes followed by regular firing at all suprathreshold current intensities. The last class consists of cells with an intermediate firing pattern (31%). These cells have two modes of firing response, regular spiking and bursting discharge, depending on the strength of stimulation and resting membrane potential. Our results show that diversity in the functional properties of DLPFC pyramidal cells may contribute to heterogeneous modes of information processing during working memory and other cognitive operations that engage the activity of cortical circuits in the superficial layers of the DLPFC.

[1]  B. Sakmann,et al.  Dendritic Spikes in Apical Dendrites of Neocortical Layer 2/3 Pyramidal Neurons , 2007, The Journal of Neuroscience.

[2]  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.

[3]  J. Seamans,et al.  Electrophysiological and morphological properties of layers V-VI principal pyramidal cells in rat prefrontal cortex in vitro , 1996, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[4]  Yu-Ming Chang,et al.  Diversity of Layer 5 Pyramidal Cells in the Prefrontal Cortex of the Rhesus Monkey : In Vitro Slice Studies , 2007 .

[5]  A. Zaitsev,et al.  Localization of calcium-binding proteins in physiologically and morphologically characterized interneurons of monkey dorsolateral prefrontal cortex. , 2005, Cerebral cortex.

[6]  Y. Kawaguchi,et al.  Cell diversity and connection specificity between callosal projection neurons in the frontal cortex , 2010, Neuroscience Research.

[7]  A. Larkman,et al.  Correlations between morphology and electrophysiology of pyramidal neurons in slices of rat visual cortex. I. Establishment of cell classes , 1990, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[8]  Yuanye Ma,et al.  Distracters impair and create working memory-related neuronal activity in the prefrontal cortex. , 2009, Cerebral cortex.

[9]  Y. Kawaguchi,et al.  Groupings of nonpyramidal and pyramidal cells with specific physiological and morphological characteristics in rat frontal cortex. , 1993, Journal of neurophysiology.

[10]  D. Henze,et al.  Dopamine increases excitability of pyramidal neurons in primate prefrontal cortex. , 2000, Journal of neurophysiology.

[11]  J. Jacobs,et al.  Regional dendritic and spine variation in human cerebral cortex: a quantitative golgi study. , 2001, Cerebral cortex.

[12]  D. Prince,et al.  Temperature dependence of intrinsic membrane properties and synaptic potentials in hippocampal CA1 neurons in vitro , 1985, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[13]  Yu-Ming Chang,et al.  Increased action potential firing rates of layer 2/3 pyramidal cells in the prefrontal cortex are significantly related to cognitive performance in aged monkeys. , 2005, Cerebral cortex.

[14]  Edi Barkai,et al.  Long-Lasting Maintenance of Learning-Induced Enhanced Neuronal Excitability: Mechanisms and Functional Significance , 2009, Molecular Neurobiology.

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

[16]  A. Baddeley.  Working memory: looking back and looking forward , 2003, Nature Reviews Neuroscience.

[17]  P. Sah,et al.  Channels underlying neuronal calcium-activated potassium currents , 2002, Progress in Neurobiology.

[18]  M. Häusser,et al.  Targeted dendrotomy reveals active and passive contributions of the dendritic tree to synaptic integration and neuronal output , 2007, Proceedings of the National Academy of Sciences.

[19]  M. L. Pucak,et al.  Synaptic targets of pyramidal neurons providing intrinsic horizontal connections in monkey prefrontal cortex , 1998, The Journal of comparative neurology.

[20]  A. Hansen,et al.  Effect of anoxia on ion distribution in the brain. , 1985, Physiological reviews.

[21]  A. Larkman,et al.  Correlations between morphology and electrophysiology of pyramidal neurons in slices of rat visual cortex. II. Electrophysiology , 1990, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[22]  D. Lewis,et al.  Parvalbumin-positive basket interneurons in monkey and rat prefrontal cortex. , 2008, Journal of neurophysiology.

[23]  A. Zaitsev,et al.  Interneuron diversity in layers 2-3 of monkey prefrontal cortex. , 2009, Cerebral cortex.

[24]  A. Zaitsev,et al.  Properties of excitatory synaptic responses in fast-spiking interneurons and pyramidal cells from monkey and rat prefrontal cortex. , 2006, Cerebral cortex.

[25]  P. Goldman-Rakic,et al.  Modulation of memory fields by dopamine Dl receptors in prefrontal cortex , 1995, Nature.

[26]  Daeyeol Lee,et al.  Neuronal basis of age-related working memory decline , 2011, Nature.

[27]  Xiao-Jing Wang.  Synaptic reverberation underlying mnemonic persistent activity , 2001, Trends in Neurosciences.

[28]  J. Luebke,et al.  Age-related increase of sIAHP in prefrontal pyramidal cells of monkeys: relationship to cognition , 2012, Neurobiology of Aging.

[29]  L. Abbott,et al.  Synaptic Depression and Cortical Gain Control , 1997, Science.

[30]  J. Lisman.  Bursts as a unit of neural information: making unreliable synapses reliable , 1997, Trends in Neurosciences.

[31]  T R Vidyasagar,et al.  Membrane properties and spike generation in rat visual cortical cells during reversible cooling , 2000, The Journal of physiology.

[32]  E. Geijo-Barrientos,et al.  Laminar Localization, Morphology, and Physiological Properties of Pyramidal Neurons that Have the Low-Threshold Calcium Current in the Guinea-Pig Medial Frontal Cortex , 1996, The Journal of Neuroscience.

[33]  E. Tanaka,et al.  Ionic mechanisms underlying the depolarizing and hyperpolarizing afterpotentials of single spike in guinea-pig cingulate cortical neurons , 1993, Neuroscience.

[34]  C. Gray,et al.  Chattering Cells: Superficial Pyramidal Neurons Contributing to the Generation of Synchronous Oscillations in the Visual Cortex , 1996, Science.

[35]  Shintaro Funahashi,et al.  Neuronal activity throughout the primate mediodorsal nucleus of the thalamus during oculomotor delayed-responses. I. Cue-, delay-, and response-period activity. , 2004, Journal of neurophysiology.

[36]  G. Hu,et al.  Electrophysiological and morphological properties of pyramidal and nonpyramidal neurons in the cat motor cortex in vitro , 1996, Neuroscience.

[37]  H. Pape,et al.  Queer current and pacemaker: the hyperpolarization-activated cation current in neurons. , 1996, Annual review of physiology.

[38]  Nelson Spruston,et al.  Stability and plasticity of intrinsic membrane properties in hippocampal CA1 pyramidal neurons: effects of internal anions , 2007, The Journal of physiology.

[39]  Alex M Thomson,et al.  Robust correlations between action potential duration and the properties of synaptic connections in layer 4 interneurones in neocortical slices from juvenile rats and adult rat and cat , 2007, The Journal of physiology.

[40]  P. Sah,et al.  FUNCTIONS OF SK CHANNELS IN CENTRAL NEURONS , 2007, Clinical and experimental pharmacology & physiology.

[41]  P. Goldman-Rakic,et al.  Intrinsic circuit organization of the major layers and sublayers of the dorsolateral prefrontal cortex in the rhesus monkey , 1995, The Journal of comparative neurology.

[42]  P. Goldman-Rakic,et al.  Common cortical and subcortical targets of the dorsolateral prefrontal and posterior parietal cortices in the rhesus monkey: evidence for a distributed neural network subserving spatially guided behavior , 1988, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[43]  F. Dudek,et al.  Electrical properties of neocortical neurons in slices from children with intractable epilepsy. , 1996, Journal of neurophysiology.

[44]  G. Elston,et al.  The Pyramidal Cell in Cognition: A Comparative Study in Human and Monkey , 2001, The Journal of Neuroscience.

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

[46]  A. Zaitsev,et al.  Electrophysiological differences between neurogliaform cells from monkey and rat prefrontal cortex. , 2007, Journal of neurophysiology.

[47]  Yasuo Kawaguchi,et al.  Firing-Pattern-Dependent Specificity of Cortical Excitatory Feed-Forward Subnetworks , 2008, The Journal of Neuroscience.

[48]  S. Nelson,et al.  Layer V neurons in mouse cortex projecting to different targets have distinct physiological properties. , 2007, Journal of neurophysiology.

[49]  J. Seamans,et al.  The principal features and mechanisms of dopamine modulation in the prefrontal cortex , 2004, Progress in Neurobiology.

[50]  J. Seamans,et al.  Dopaminergic modulation of short-term synaptic plasticity in fast-spiking interneurons of primate dorsolateral prefrontal cortex. , 2005, Journal of neurophysiology.

[51]  K. Hikosaka,et al.  Increase of extracellular dopamine in primate prefrontal cortex during a working memory task. , 1997, Journal of neurophysiology.

[52]  R. Foehring,et al.  Correlation of physiologically and morphologically identified neuronal types in human association cortex in vitro. , 1991, Journal of neurophysiology.

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

[54]  B. Connors.  Initiation of synchronized neuronal bursting in neocortex , 1984, Nature.

[55]  D. Lewis,et al.  GABA transporter GAT1 prevents spillover at proximal and distal GABA synapses onto primate prefrontal cortex neurons. , 2009, Journal of neurophysiology.

[56]  J. Fuster.  Network memory , 1997, Trends in Neurosciences.

[57]  J. Grafman,et al.  Human prefrontal cortex: processing and representational perspectives , 2003, Nature Reviews Neuroscience.

[58]  P. Schwindt,et al.  Quantitative analysis of firing properties of pyramidal neurons from layer 5 of rat sensorimotor cortex. , 1997, Journal of neurophysiology.

[59]  D. Lewis,et al.  Horizontal synaptic connections in monkey prefrontal cortex: an in vitro electrophysiological study. , 2000, Cerebral cortex.

[60]  J. H. Ward.  Hierarchical Grouping to Optimize an Objective Function , 1963 .

[61]  Yves Gioanni,et al.  Electrophysiological properties of pyramidal neurons in the rat prefrontal cortex: an in vivo intracellular recording study. , 2002, Cerebral cortex.

[62]  S. Siegelbaum,et al.  Hyperpolarization-activated cation currents: from molecules to physiological function. , 2003, Annual review of physiology.

[63]  A. A. Velumian,et al.  Whole-cell recording of the Ca2+-dependent slow afterhyperpolarization in hippocampal neurones: effects of internally applied anions , 1994, Pflügers Archiv.

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

[65]  Xiao-Jing Wang,et al.  Cannabinoid-mediated disinhibition and working memory: dynamical interplay of multiple feedback mechanisms in a continuous attractor model of prefrontal cortex. , 2007, Cerebral cortex.

[66]  R. Desimone,et al.  Neural Mechanisms of Visual Working Memory in Prefrontal Cortex of the Macaque , 1996, The Journal of Neuroscience.

[67]  B. Connors,et al.  Correlation between intrinsic firing patterns and thalamocortical synaptic responses of neurons in mouse barrel cortex , 1992, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[68]  P. Goldman-Rakic.  Regional and cellular fractionation of working memory. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[69]  Bard Ermentrout,et al.  Spatially Structured Activity in Synaptically Coupled Neuronal Networks: I. Traveling Fronts and Pulses , 2001, SIAM J. Appl. Math..

[70]  Daeyeol Lee,et al.  Beyond working memory: the role of persistent activity in decision making , 2010, Trends in Cognitive Sciences.

[71]  B. Connors,et al.  Repetitive burst-firing neurons in the deep layers of mouse somatosensory cortex , 1989, Neuroscience Letters.

[72]  K. Svoboda,et al.  Development of intrinsic properties and excitability of layer 2/3 pyramidal neurons during a critical period for sensory maps in rat barrel cortex. , 2004, Journal of neurophysiology.

[73]  O. Hikosaka,et al.  Role of the basal ganglia in the control of purposive saccadic eye movements. , 2000, Physiological reviews.

[74]  Helen Barbas,et al.  Effects of normal aging on prefrontal area 46 in the rhesus monkey , 2010, Brain Research Reviews.

[75]  German Barrionuevo,et al.  Synaptic targets of the intrinsic axon collaterals of supragranular pyramidal neurons in monkey prefrontal cortex , 2001, The Journal of comparative neurology.

[76]  P. Goldman-Rakic.  Cellular basis of working memory , 1995, Neuron.

[77]  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.

[78]  A. Zaitsev,et al.  Functional maturation of excitatory synapses in layer 3 pyramidal neurons during postnatal development of the primate prefrontal cortex. , 2008, Cerebral cortex.

[79]  Thomas K. Berger,et al.  Brief Bursts Self-Inhibit and Correlate the Pyramidal Network , 2010, PLoS biology.

[80]  M Steriade,et al.  Electrophysiology of cat association cortical cells in vivo: intrinsic properties and synaptic responses. , 1993, Journal of neurophysiology.

[81]  J. B. Levitt,et al.  Patterns of intrinsic and associational circuitry in monkey prefrontal cortex , 1996, The Journal of comparative neurology.

[82]  German Barrionuevo,et al.  Selective reduction by dopamine of excitatory synaptic inputs to pyramidal neurons in primate prefrontal cortex , 2002, The Journal of physiology.

[83]  G. Elston.  Cortex, cognition and the cell: new insights into the pyramidal neuron and prefrontal function. , 2003, Cerebral cortex.

[84]  T. Sawaguchi,et al.  The effects of dopamine and its antagonists on directional delay-period activity of prefrontal neurons in monkeys during an oculomotor delayed-response task , 2001, Neuroscience Research.

[85]  D. Lewis,et al.  Cluster analysis-based physiological classification and morphological properties of inhibitory neurons in layers 2-3 of monkey dorsolateral prefrontal cortex. , 2005, Journal of neurophysiology.

[86]  M. Steriade,et al.  Dynamic properties of corticothalamic neurons and local cortical interneurons generating fast rhythmic (30-40 Hz) spike bursts. , 1998, Journal of neurophysiology.

[87]  P. Goldman-Rakic,et al.  Selective D2 Receptor Actions on the Functional Circuitry of Working Memory , 2004, Science.

[88]  E. Miller,et al.  THE PREFRONTAL CORTEX AND COGNITIVE CONTROL , 2000 .

[89]  Richard A. Johnson,et al.  Applied Multivariate Statistical Analysis , 1983 .

[90]  J. Callaway,et al.  Effects of temperature on calcium transients and Ca2+-dependent afterhyperpolarizations in neocortical pyramidal neurons. , 2005, Journal of neurophysiology.

[91]  D. McCormick,et al.  Ionic Mechanisms Underlying Repetitive High-Frequency Burst Firing in Supragranular Cortical Neurons , 2000, The Journal of Neuroscience.