Spatial Profile of Excitatory and Inhibitory Synaptic Connectivity in Mouse Primary Auditory Cortex

The role of local cortical activity in shaping neuronal responses is controversial. Among other questions, it is unknown how the diverse response patterns reported in vivo—lateral inhibition in some cases, approximately balanced excitation and inhibition (co-tuning) in others—compare to the local spread of synaptic connectivity. Excitatory and inhibitory activity might cancel each other out, or, whether one outweighs the other, receptive field properties might be substantially affected. As a step toward addressing this question, we used multiple intracellular recording in mouse primary auditory cortical slices to map synaptic connectivity among excitatory pyramidal cells and the two broad classes of inhibitory cells, fast-spiking (FS) and non-FS cells in the principal input layer. Connection probability was distance-dependent; the spread of connectivity, parameterized by Gaussian fits to the data, was comparable for all cell types, ranging from 85 to 114 μm. With brief stimulus trains, unitary synapses formed by FS interneurons were stronger than other classes of synapses; synapse strength did not correlate with distance between cells. The physiological data were qualitatively consistent with predictions derived from anatomical reconstruction. We also analyzed the truncation of neuronal processes due to slicing; overall connectivity was reduced but the spatial pattern was unaffected. The comparable spatial patterns of connectivity and relatively strong excitatory-inhibitory interconnectivity are consistent with a theoretical model where either lateral inhibition or co-tuning can predominate, depending on the structure of the input.

[1]  M. Marín‐padilla Origin of the pericellular baskets of the pyramidal cells of the human motor cortex: a Golgi study. , 1969, Brain research.

[2]  H. Markram,et al.  Differential signaling via the same axon of neocortical pyramidal neurons. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[3]  Anne-Marie M Oswald,et al.  Development of inhibitory timescales in auditory cortex. , 2011, Cerebral cortex.

[4]  W. Wong The tangential organization of dendrites and axons in three auditory areas of the cat's cerebral cortex. , 1967, Journal of anatomy.

[5]  N Suga,et al.  Peripheral specialization for fine analysis of doppler-shifted echoes in the auditory system of the "CF-FM" bat Pteronotus parnellii. , 1975, The Journal of experimental biology.

[6]  H. Markram,et al.  Physiology and anatomy of synaptic connections between thick tufted pyramidal neurones in the developing rat neocortex. , 1997, The Journal of physiology.

[7]  T. Harkany,et al.  Pyramidal cell communication within local networks in layer 2/3 of rat neocortex , 2003, The Journal of physiology.

[8]  J. Lübke,et al.  Columnar Organization of Dendrites and Axons of Single and Synaptically Coupled Excitatory Spiny Neurons in Layer 4 of the Rat Barrel Cortex , 2000, The Journal of Neuroscience.

[9]  P. Goldman-Rakic,et al.  The synaptology of parvalbumin‐immunoreactive neurons in the primate prefrontal cortex , 1992, The Journal of comparative neurology.

[10]  G. Ehret Development of absolute auditory thresholds in the house mouse (Mus musculus). , 1976, Journal of the American Audiology Society.

[11]  T. Wiesel,et al.  Functional architecture of macaque monkey visual cortex , 1977 .

[12]  A. Reyes,et al.  Synaptic mechanisms underlying auditory processing , 2006, Current Opinion in Neurobiology.

[13]  Robert B. Levy,et al.  Coexistence of Lateral and Co-Tuned Inhibitory Configurations in Cortical Networks , 2011, PLoS Comput. Biol..

[14]  D. Chklovskii,et al.  Neurogeometry and potential synaptic connectivity , 2005, Trends in Neurosciences.

[15]  S. Hestrin,et al.  Intracortical circuits of pyramidal neurons reflect their long-range axonal targets , 2009, Nature.

[16]  N Suga,et al.  Sharpening of frequency tuning by inhibition in the thalamic auditory nucleus of the mustached bat. , 1997, Journal of neurophysiology.

[17]  B. Sakmann,et al.  The Excitatory Neuronal Network of Rat Layer 4 Barrel Cortex , 2000, The Journal of Neuroscience.

[18]  B Sakmann,et al.  Functionally Independent Columns of Rat Somatosensory Barrel Cortex Revealed with Voltage-Sensitive Dye Imaging , 2001, The Journal of Neuroscience.

[19]  R. Yuste,et al.  Neural Circuits Original Research Article Materials and Methods Preparation of Brain Slices , 2022 .

[20]  D. Prince,et al.  Cholinergic switching within neocortical inhibitory networks. , 1998, Science.

[21]  Boris Barbour,et al.  Combining loose cell-attached stimulation and recording , 2000, Journal of Neuroscience Methods.

[22]  E. White Cortical Circuits , 1989, Birkhäuser Boston.

[23]  Alex S. Ferecskó,et al.  The fractions of short- and long-range connections in the visual cortex , 2009, Proceedings of the National Academy of Sciences.

[24]  R. Metherate,et al.  Intrinsic electrophysiology of neurons in thalamorecipient layers of developing rat auditory cortex. , 1999, Brain research. Developmental brain research.

[25]  J. Budd,et al.  A numerical analysis of the geniculocortical input to striate cortex in the monkey. , 1994, Cerebral cortex.

[26]  J. McGee,et al.  Frequency- and level-dependent changes in auditory brainstem responses (ABRS) in developing mice. , 2006, The Journal of the Acoustical Society of America.

[27]  H. Markram,et al.  Anatomical, physiological and molecular properties of Martinotti cells in the somatosensory cortex of the juvenile rat , 2004, The Journal of physiology.

[28]  Wong Wc The tangential organization of dendrites and axons in three auditory areas of the cat's cerebral cortex. , 1967 .

[29]  A. Peters,et al.  Numerical relationships between geniculocortical afferents and pyramidal cell modules in cat primary visual cortex. , 1993, Cerebral cortex.

[30]  Brent Doiron,et al.  Spatial Profile and Differential Recruitment of GABAB Modulate Oscillatory Activity in Auditory Cortex , 2009, The Journal of Neuroscience.

[31]  S. Cruikshank,et al.  Auditory thalamocortical synaptic transmission in vitro. , 2002, Journal of neurophysiology.

[32]  G. Blasdel,et al.  Termination of afferent axons in macaque striate cortex , 1983, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[33]  Bernhard Hellwig,et al.  A quantitative analysis of the local connectivity between pyramidal neurons in layers 2/3 of the rat visual cortex , 2000, Biological Cybernetics.

[34]  M. Colonnier THE TANGENTIAL ORGANIZATION OF THE VISUAL CORTEX. , 1964, Journal of anatomy.

[35]  Henry Markram,et al.  Deriving physical connectivity from neuronal morphology , 2003, Biological Cybernetics.

[36]  G. Fishell,et al.  Three groups of interneurons account for nearly 100% of neocortical GABAergic neurons , 2011, Developmental neurobiology.

[37]  E. Young,et al.  Responses to tones and noise of single cells in dorsal cochlear nucleus of unanesthetized cats. , 1976, Journal of neurophysiology.

[38]  A. Agmon,et al.  Distinct Subtypes of Somatostatin-Containing Neocortical Interneurons Revealed in Transgenic Mice , 2006, The Journal of Neuroscience.

[39]  G. Knott,et al.  Experience and Activity-Dependent Maturation of Perisomatic GABAergic Innervation in Primary Visual Cortex during a Postnatal Critical Period , 2004, The Journal of Neuroscience.

[40]  K. Harris,et al.  Slices Have More Synapses than Perfusion-Fixed Hippocampus from both Young and Mature Rats , 1999, The Journal of Neuroscience.

[41]  N. Seidah,et al.  Regulation by gastric acid of the processing of progastrin‐derived peptides in rat antral mucosa , 1997, The Journal of physiology.

[42]  R. Yuste,et al.  Dense, Unspecific Connectivity of Neocortical Parvalbumin-Positive Interneurons: A Canonical Microcircuit for Inhibition? , 2011, The Journal of Neuroscience.

[43]  J. Kelly,et al.  Organization of auditory cortex in the albino rat: sound frequency. , 1988, Journal of neurophysiology.

[44]  H. Markram,et al.  The neocortical microcircuit as a tabula rasa. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[45]  Erika E Fanselow,et al.  Selective, state-dependent activation of somatostatin-expressing inhibitory interneurons in mouse neocortex. , 2008, Journal of neurophysiology.

[46]  T. Hromádka,et al.  Sparse Representation of Sounds in the Unanesthetized Auditory Cortex , 2008, PLoS biology.

[47]  H. Markram,et al.  Organizing principles for a diversity of GABAergic interneurons and synapses in the neocortex. , 2000, Science.

[48]  S. Levay,et al.  Synaptic organization of claustral and geniculate afferents to the visual cortex of the cat , 1986, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[49]  U. Mitzdorf,et al.  Functional anatomy of the inferior colliculus and the auditory cortex: current source density analyses of click-evoked potentials , 1984, Hearing Research.

[50]  T. Hackett,et al.  Linking Topography to Tonotopy in the Mouse Auditory Thalamocortical Circuit , 2011, The Journal of Neuroscience.

[51]  Guangying K. Wu,et al.  Lateral Sharpening of Cortical Frequency Tuning by Approximately Balanced Inhibition , 2008, Neuron.

[52]  C. Petersen The Functional Organization of the Barrel Cortex , 2007, Neuron.

[53]  C. Koch,et al.  Recurrent excitation in neocortical circuits , 1995, Science.

[54]  R. Yuste,et al.  Dense Inhibitory Connectivity in Neocortex , 2011, Neuron.

[55]  J. Winer,et al.  Auditory thalamocortical projections in the cat: Laminar and areal patterns of input , 2000, The Journal of comparative neurology.

[56]  Christoph E. Schreiner,et al.  Developmental sensory experience balances cortical excitation and inhibition , 2010, Nature.

[57]  B. Connors,et al.  Two dynamically distinct inhibitory networks in layer 4 of the neocortex. , 2003, Journal of neurophysiology.

[58]  M. Marín‐padilla Double origin of the pericellular baskets of the pyramidal cells of the human motor cortex: a Golgi study. , 1969, Brain research.

[59]  R. Shapley,et al.  New perspectives on the mechanisms for orientation selectivity , 1997, Current Opinion in Neurobiology.

[60]  J. Deuchars,et al.  Single axon excitatory postsynaptic potentials in neocortical interneurons exhibit pronounced paired pulse facilitation , 1993, Neuroscience.

[61]  P. Somogyi,et al.  Target-cell-specific facilitation and depression in neocortical circuits , 1998, Nature Neuroscience.

[62]  Y. Kawaguchi,et al.  Cortical Inhibitory Cell Types Differentially Form Intralaminar and Interlaminar Subnetworks withExcitatory Neurons , 2009, The Journal of Neuroscience.

[63]  Y. Kubota,et al.  Correlation of physiological subgroupings of nonpyramidal cells with parvalbumin- and calbindinD28k-immunoreactive neurons in layer V of rat frontal cortex. , 1993, Journal of neurophysiology.

[64]  Robert Shapley,et al.  The dynamics of visual responses in the primary visual cortex. , 2007, Progress in brain research.

[65]  Y. Kubota,et al.  GABAergic cell subtypes and their synaptic connections in rat frontal cortex. , 1997, Cerebral cortex.

[66]  B. Sakmann,et al.  Patch-clamp recordings from the soma and dendrites of neurons in brain slices using infrared video microscopy , 1993, Pflügers Archiv.

[67]  Karen L. Smith,et al.  Novel Hippocampal Interneuronal Subtypes Identified Using Transgenic Mice That Express Green Fluorescent Protein in GABAergic Interneurons , 2000, The Journal of Neuroscience.

[68]  P. Somogyi,et al.  Synaptic target selectivity and input of GABAergic basket and bistratified interneurons in the CA1 area of the rat hippocampus , 1996, Hippocampus.

[69]  G. Shepherd,et al.  Geometric and functional organization of cortical circuits , 2005, Nature Neuroscience.

[70]  C. Schreiner,et al.  Modular organization of frequency integration in primary auditory cortex. , 2000, Annual review of neuroscience.

[71]  KF Jensen,et al.  Terminal arbors of axons projecting to the somatosensory cortex of the adult rat. I. The normal morphology of specific thalamocortical afferents , 1987, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[72]  R. Metherate,et al.  Auditory thalamocortical transmission is reliable and temporally precise. , 2005, Journal of neurophysiology.

[73]  Rafael Yuste,et al.  Global dendritic calcium spikes in mouse layer 5 low threshold spiking interneurones: implications for control of pyramidal cell bursting , 2004, The Journal of physiology.

[74]  A. Reyes,et al.  Linking the Response Properties of Cells in Auditory Cortex with Network Architecture: Cotuning versus Lateral Inhibition , 2008, The Journal of Neuroscience.

[75]  J. Deuchars,et al.  Properties of single axon excitatory postsynaptic potentials elicited in spiny interneurons by action potentials in pyramidal neurons in slices of rat neocortex , 1995, Neuroscience.

[76]  Anne E Takesian,et al.  Presynaptic GABAB Receptors Regulate Experience-Dependent Development of Inhibitory Short-Term Plasticity , 2010, The Journal of Neuroscience.

[77]  Mu Zhou,et al.  Fine-tuning of pre-balanced excitation and inhibition during auditory cortical development , 2010, Nature.

[78]  A. Zador,et al.  Balanced inhibition underlies tuning and sharpens spike timing in auditory cortex , 2003, Nature.

[79]  R. Yuste,et al.  Two-photon mapping of neural circuits. , 2011, Cold Spring Harbor protocols.

[80]  D. Hubel,et al.  Ferrier lecture - Functional architecture of macaque monkey visual cortex , 1977, Proceedings of the Royal Society of London. Series B. Biological Sciences.

[81]  Anne-Marie M Oswald,et al.  Maturation of intrinsic and synaptic properties of layer 2/3 pyramidal neurons in mouse auditory cortex. , 2008, Journal of neurophysiology.

[82]  Shihab A. Shamma,et al.  Dichotomy of functional organization in the mouse auditory cortex , 2010, Nature Neuroscience.

[83]  Erika E Fanselow,et al.  The roles of somatostatin-expressing (GIN) and fast-spiking inhibitory interneurons in UP-DOWN states of mouse neocortex. , 2010, Journal of neurophysiology.

[84]  Thomas K. Berger,et al.  A synaptic organizing principle for cortical neuronal groups , 2011, Proceedings of the National Academy of Sciences.