Layer 6 Corticothalamic Neurons Activate a Cortical Output Layer, Layer 5a

Layer 6 corticothalamic neurons are thought to modulate incoming sensory information via their intracortical axons targeting the major thalamorecipient layer of the neocortex, layer 4, and via their long-range feedback projections to primary sensory thalamic nuclei. However, anatomical reconstructions of individual layer 6 corticothalamic (L6 CT) neurons include examples with axonal processes ramifying within layer 5, and the relative input of the overall population of L6 CT neurons to layers 4 and 5 is not well understood. We compared the synaptic impact of L6 CT cells on neurons in layers 4 and 5. We found that the axons of L6 CT neurons densely ramified within layer 5a in both visual and somatosensory cortices of the mouse. Optogenetic activation of corticothalamic neurons generated large EPSPs in pyramidal neurons in layer 5a. In contrast, excitatory neurons in layer 4 exhibited weak excitation or disynaptic inhibition. Fast-spiking parvalbumin-positive cells in both layer 5a and layer 4 were also strongly activated by L6 CT neurons. The overall effect of L6 CT activation was to suppress layer 4 while eliciting action potentials in layer 5a pyramidal neurons. Together, our data indicate that L6 CT neurons strongly activate an output layer of the cortex.

[1]  K. Harris,et al.  Cortical connectivity and sensory coding , 2013, Nature.

[2]  R. Guillery,et al.  Thalamic Relay Functions and Their Role in Corticocortical Communication Generalizations from the Visual System , 2002, Neuron.

[3]  R. Douglas,et al.  A Quantitative Map of the Circuit of Cat Primary Visual Cortex , 2004, The Journal of Neuroscience.

[4]  A. Sillito,et al.  Differential properties of cells in the feline primary visual cortex providing the corticofugal feedback to the lateral geniculate nucleus and visual claustrum , 1995, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[5]  T. Wiesel,et al.  The Sharpey-Schafer lecture. Morphological basis of visual cortical function. , 1983, Quarterly journal of experimental physiology.

[6]  J. C. Anderson,et al.  Map of the synapses formed with the dendrites of spiny stellate neurons of cat visual cortex , 1994, The Journal of comparative neurology.

[7]  J. C. Anderson,et al.  Polyneuronal innervation of spiny stellate neurons in cat visual cortex , 1994, The Journal of comparative neurology.

[8]  C. Petersen,et al.  The Excitatory Neuronal Network of the C2 Barrel Column in Mouse Primary Somatosensory Cortex , 2009, Neuron.

[9]  E. White,et al.  Intrinsic circuitry involving the local axon collaterals of corticothalamic projection cells in mouse SmI cortex , 1987, The Journal of comparative neurology.

[10]  D Ferster,et al.  Augmenting responses evoked in area 17 of the cat by intracortical axon collaterals of cortico‐geniculate cells. , 1985, The Journal of physiology.

[11]  K. Martin,et al.  Excitatory synaptic inputs to spiny stellate cells in cat visual cortex , 1996, Nature.

[12]  E. Callaway.  Local circuits in primary visual cortex of the macaque monkey. , 1998, Annual review of neuroscience.

[13]  B. Sakmann,et al.  Three-dimensional axon morphologies of individual layer 5 neurons indicate cell type-specific intracortical pathways for whisker motion and touch , 2011, Proceedings of the National Academy of Sciences.

[14]  D. Feldmeyer.  Excitatory neuronal connectivity in the barrel cortex , 2012, Front. Neuroanat..

[15]  M. Deschenes,et al.  Intracortical Axonal Projections of Lamina VI Cells of the Primary Somatosensory Cortex in the Rat: A Single-Cell Labeling Study , 1997, The Journal of Neuroscience.

[16]  George Paxinos,et al.  The Mouse Brain in Stereotaxic Coordinates , 2001 .

[17]  M. Sirota,et al.  Three Channels of Corticothalamic Communication during Locomotion , 2005, The Journal of Neuroscience.

[18]  Alex M. Thomson,et al.  Neocortical Layer 6, A Review , 2010, Front. Neuroanat..

[19]  T. Kaneko,et al.  Green fluorescent protein expression and colocalization with calretinin, parvalbumin, and somatostatin in the GAD67‐GFP knock‐in mouse , 2003, The Journal of comparative neurology.

[20]  L C Katz,et al.  Local circuitry of identified projection neurons in cat visual cortex brain slices , 1987, The Journal of neuroscience : the official journal of the Society for Neuroscience.

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

[22]  Corbett Bennett,et al.  Prolonged Disynaptic Inhibition in the Cortex Mediated by Slow, Non-α7 Nicotinic Excitation of a Specific Subset of Cortical Interneurons , 2012, The Journal of Neuroscience.

[23]  Shawn R. Olsen,et al.  Gain control by layer six in cortical circuits of vision , 2012, Nature.

[24]  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.

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

[26]  A. Sillito,et al.  Always returning: feedback and sensory processing in visual cortex and thalamus , 2006, Trends in Neurosciences.

[27]  T. Wiesel,et al.  Patterns of synaptic input to layer 4 of cat striate cortex , 1984, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[28]  Jochen F. Staiger,et al.  Recurrent axon collaterals of corticothalamic projection neurons in rat primary somatosensory cortex contribute to excitatory and inhibitory feedback-loops , 1996, Anatomy and Embryology.

[29]  Bryan M. Hooks,et al.  Laminar Analysis of Excitatory Local Circuits in Vibrissal Motor and Sensory Cortical Areas , 2011, PLoS biology.

[30]  P. Somogyi.  Synaptic Organization of GABAergic Neurons and GABA A Receptors in the Lateral Geniculate Nucleus and Visual Cortex , 2006 .

[31]  R. Douglas,et al.  Neuronal circuits of the neocortex. , 2004, Annual review of neuroscience.

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

[33]  W. Usrey,et al.  Emerging views of corticothalamic function , 2008, Current Opinion in Neurobiology.

[34]  Charles R. Gerfen,et al.  Targeting Cre Recombinase to Specific Neuron Populations with Bacterial Artificial Chromosome Constructs , 2007, The Journal of Neuroscience.

[35]  Shawn R. Olsen,et al.  Translaminar Inhibitory Cells Recruited by Layer 6 Corticothalamic Neurons Suppress Visual Cortex , 2014, Neuron.

[36]  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.

[37]  S. Sherman,et al.  Thalamic relays and cortical functioning. , 2005, Progress in brain research.

[38]  J. Rubenstein,et al.  Pyramidal Neurons in Prefrontal Cortex Receive Subtype-Specific Forms of Excitation and Inhibition , 2014, Neuron.

[39]  Arto V. Nurmikko,et al.  Pathway-Specific Feedforward Circuits between Thalamus and Neocortex Revealed by Selective Optical Stimulation of Axons , 2010, Neuron.

[40]  K. Martin,et al.  Map of the synapses onto layer 4 basket cells of the primary visual cortex of the cat , 1997, The Journal of comparative neurology.

[41]  Allan R. Jones,et al.  A toolbox of Cre-dependent optogenetic transgenic mice for light-induced activation and silencing , 2012, Nature Neuroscience.

[42]  K. Svoboda,et al.  Interdigitated Paralemniscal and Lemniscal Pathways in the Mouse Barrel Cortex , 2006, PLoS biology.

[43]  Allan R. Jones,et al.  A robust and high-throughput Cre reporting and characterization system for the whole mouse brain , 2009, Nature Neuroscience.