Local-Circuit Phenotypes of Layer 5 Neurons in Motor-Frontal Cortex of YFP-H Mice

Layer 5 pyramidal neurons comprise an important but heterogeneous group of cortical projection neurons. In motor-frontal cortex, these neurons are centrally involved in the cortical control of movement. Recent studies indicate that local excitatory networks in mouse motor-frontal cortex are dominated by descending pathways from layer 2/3 to 5. However, those pathways were identified in experiments involving unlabeled neurons in wild type mice. Here, to explore the possibility of class-specific connectivity in this descending pathway, we mapped the local sources of excitatory synaptic input to a genetically labeled population of cortical neurons: YFP-positive layer 5 neurons of YFP-H mice. We found, first, that in motor cortex, YFP-positive neurons were distributed in a double blade, consistent with the idea of layer 5B having greater thickness in frontal neocortex. Second, whereas unlabeled neurons in upper layer 5 received their strongest inputs from layer 2, YFP-positive neurons in the upper blade received prominent layer 3 inputs. Third, YFP-positive neurons exhibited distinct electrophysiological properties, including low spike frequency adaptation, as reported previously. Our results with this genetically labeled neuronal population indicate the presence of distinct local-circuit phenotypes among layer 5 pyramidal neurons in mouse motor-frontal cortex, and present a paradigm for investigating local circuit organization in other genetically labeled populations of cortical neurons.

[1]  Z. Molnár,et al.  Towards the classification of subpopulations of layer V pyramidal projection neurons , 2006, Neuroscience Research.

[2]  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.

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

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

[5]  V. Caviness,et al.  Interhemispheric neocortical connections of the corpus callosum in the normal mouse: A study based on anterograde and retrograde methods , 1975, The Journal of comparative neurology.

[6]  E. Callaway,et al.  Photostimulation using caged glutamate reveals functional circuitry in living brain slices. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[7]  A Keller,et al.  Intrinsic synaptic organization of the motor cortex. , 1993, Cerebral cortex.

[8]  P. Arlotta,et al.  Fezl Is Required for the Birth and Specification of Corticospinal Motor Neurons , 2005, Neuron.

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

[10]  V. Caviness,et al.  Interhemispheric neocortical connections of the corpus callosum in the reeler mutant mouse: A study based on anterograde and retrograde methods , 1975, The Journal of comparative neurology.

[11]  D. Tank,et al.  Imaging Large-Scale Neural Activity with Cellular Resolution in Awake, Mobile Mice , 2007, Neuron.

[12]  C. Quattrocchi,et al.  Reelin Promotes Hippocampal Dendrite Development through the VLDLR/ApoER2-Dab1 Pathway , 2004, Neuron.

[13]  Robert H. Brown,et al.  Molecular biology of amyotrophic lateral sclerosis: insights from genetics , 2006, Nature Reviews Neuroscience.

[14]  K. Svoboda,et al.  Channelrhodopsin-2–assisted circuit mapping of long-range callosal projections , 2007, Nature Neuroscience.

[15]  R. Kötter,et al.  Layer-Specific Intracolumnar and Transcolumnar Functional Connectivity of Layer V Pyramidal Cells in Rat Barrel Cortex , 2001, The Journal of Neuroscience.

[16]  Paola Arlotta,et al.  Neuronal Subtype-Specific Genes that Control Corticospinal Motor Neuron Development In Vivo , 2005, Neuron.

[17]  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.

[18]  E. G. Jones,et al.  The organization and postnatal development of the commissural projection of the rat somatic sensory cortex , 1976, The Journal of comparative neurology.

[19]  Joshua C. Brumberg,et al.  The sensorimotor slice , 2007, Journal of Neuroscience Methods.

[20]  M. Schieber Constraints on somatotopic organization in the primary motor cortex. , 2001, Journal of neurophysiology.

[21]  J. D. Macklis,et al.  Large‐scale maintenance of dual projections by callosal and frontal cortical projection neurons in adult mice , 2005, The Journal of comparative neurology.

[22]  J. Sanes,et al.  PDAPP; YFP double transgenic mice: A tool to study amyloid‐β associated changes in axonal, dendritic, and synaptic structures , 2003, The Journal of comparative neurology.

[23]  Timothy H Murphy,et al.  Rapid Reversible Changes in Dendritic Spine Structure In Vivo Gated by the Degree of Ischemia , 2005, The Journal of Neuroscience.

[24]  C. G. Phillips,et al.  Corticospinal neurones. Their role in movement. , 1977, Monographs of the Physiological Society.

[25]  D. Prince,et al.  Heterogeneity of rat corticospinal neurons , 1993, The Journal of comparative neurology.

[26]  H Asanuma,et al.  Information processing within the motor cortex. II. Intracortical connections between neurons receiving somatosensory cortical input and motor output neurons of the cortex , 1994, The Journal of comparative neurology.

[27]  Richard R. Ribchester,et al.  Quantitative and qualitative analysis of Wallerian degeneration using restricted axonal labelling in YFP-H mice , 2004, Journal of Neuroscience Methods.

[28]  Karel Svoboda,et al.  Circuit Analysis of Experience-Dependent Plasticity in the Developing Rat Barrel Cortex , 2003, Neuron.

[29]  J. Sanes,et al.  A compensatory subpopulation of motor neurons in a mouse model of amyotrophic lateral sclerosis , 2005, The Journal of comparative neurology.

[30]  T. Kaneko,et al.  Predominant information transfer from layer III pyramidal neurons to corticospinal neurons , 2000, The Journal of comparative neurology.

[31]  T. Powell,et al.  The intrinsic connections of the cortex of area 4 of the monkey. , 1978, Brain : a journal of neurology.

[32]  Takeshi Kaneko,et al.  Intracellularly labeled pyramidal neurons in the cortical areas projecting to the spinal cord II. Intra- and juxta-columnar projection of pyramidal neurons to corticospinal neurons , 2004, Neuroscience Research.

[33]  N. Kasthuri,et al.  Long-term dendritic spine stability in the adult cortex , 2002, Nature.

[34]  S. Nelson,et al.  Molecular taxonomy of major neuronal classes in the adult mouse forebrain , 2006, Nature Neuroscience.

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

[36]  A. Thomson,et al.  Functional Maps of Neocortical Local Circuitry , 2007, Front. Neurosci..

[37]  S P Wise,et al.  Size, laminar and columnar distribution of efferent cells in the sensory‐motor cortex of monkeys , 1977, The Journal of comparative neurology.

[38]  M. Pericak-Vance,et al.  The gene encoding alsin, a protein with three guanine-nucleotide exchange factor domains, is mutated in a form of recessive amyotrophic lateral sclerosis , 2001, Nature Genetics.

[39]  G. Feng,et al.  Imaging Neuronal Subsets in Transgenic Mice Expressing Multiple Spectral Variants of GFP , 2000, Neuron.

[40]  R. Ribchester,et al.  Late onset distal axonal swelling in YFP-H transgenic mice , 2009, Neurobiology of Aging.

[41]  Bertrand Fontaine,et al.  Spastin, a new AAA protein, is altered in the most frequent form of autosomal dominant spastic paraplegia , 1999, Nature Genetics.

[42]  Jianing Yu,et al.  Top-down laminar organization of the excitatory network in motor cortex , 2008, Nature Neuroscience.

[43]  George J Augustine,et al.  Imaging synaptic inhibition in transgenic mice expressing the chloride indicator, Clomeleon , 2006, Brain cell biology.

[44]  V. Caviness Architectonic map of neocortex of the normal mouse , 1975, The Journal of comparative neurology.

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

[46]  Pat Levitt,et al.  Anatomical abnormalities in dopaminoceptive regions of the cerebral cortex of dopamine D1 receptor mutant mice , 2005, The Journal of comparative neurology.