The motor cortex (MC) functions as a major node in the cortical sensorimotor network. The specific circuits and synaptic mechanisms carrying long-range excitatory projections from sensory/association areas to key cell classes in MC such as corticospinal neurons have not yet been identified. Research on cortical sensory processing has previously established the concept of multiple pathways carrying spatial and non-spatial information from primary sensory to higher-order parietal areas, but how these excitatory projections from these areas converge on the cortical motor system remains poorly understood. Here we propose an experimental program designed to elucidate the cell-type specific connectivity underlying long-range corticocortical projections from higher-order sensory/association areas in parietal cortex to identified classes of MC neurons, focusing on corticospinal neurons. We will approach this overall goal using the mouse as our experimental model, retrograde and optogenetic labeling, and targeted opto-physiological recordings of functional synaptic connectivity in select pathways.
Our aims are: (1) Determine the synaptic organization of retrosplenial cortex (RSC) projections to MC. (2) Define the input-output organization of RSC as a visuo-motor relay to MC. (3) Determine the synaptic organization of S2 inputs to MC. (4) Define the input-output organization of S2 corticospinal neurons. The proposed research program is highly innovative, we believe, because it brings together powerful new techniques to tackle an important, but experimentally previously inaccessible, issue in the field of sensorimotor research: the specific cellular mechanisms mediating corticocortical communication from higher-order sensory/association areas to motor cortical networks. The proposed research is significant because it will generate foundational knowledge about the macro- and microcircuit basis for feedforward corticocortical excitation of specific classes of MC neurons by higher-order sensory/association areas involved in sensorimotor integration.
The proposed research on motor cortex (MC) circuits is directly relevant to public health because pathology in these circuits severely impairs the control of voluntary movements, causing paralysis and other movement disorders. Here we propose a systematic, quantitative experimental approach to elucidate basic mechanisms and pathways in mammalian MC at the cellular level. This research is relevant to those aspects of the NIH mission aimed at improving health through understanding pathophysiological mechanisms in disorders causing disability, and to the NINDS mission to unravel the complexities of information transfer within the brain and gain a greater understanding of brain mechanisms underlying higher mental functions and complex behaviors.
|Neymotin, Samuel A; Suter, Benjamin A; Dura-Bernal, Salvador et al. (2017) Optimizing computer models of corticospinal neurons to replicate in vitro dynamics. J Neurophysiol 117:148-162|
|Heuermann, Robert J; Jaramillo, Thomas C; Ying, Shui-Wang et al. (2016) Reduction of thalamic and cortical Ih by deletion of TRIP8b produces a mouse model of human absence epilepsy. Neurobiol Dis 85:81-92|
|Yamawaki, Naoki; Radulovic, Jelena; Shepherd, Gordon M G (2016) A Corticocortical Circuit Directly Links Retrosplenial Cortex to M2 in the Mouse. J Neurosci 36:9365-74|
|Yamawaki, Naoki; Suter, Benjamin A; Wickersham, Ian R et al. (2016) Combining Optogenetics and Electrophysiology to Analyze Projection Neuron Circuits. Cold Spring Harb Protoc 2016:pdb.prot090084|
|Suter, Benjamin A; Shepherd, Gordon M G (2015) Reciprocal interareal connections to corticospinal neurons in mouse M1 and S2. J Neurosci 35:2959-74|
|Jovasevic, Vladimir; Corcoran, Kevin A; Leaderbrand, Katherine et al. (2015) GABAergic mechanisms regulated by miR-33 encode state-dependent fear. Nat Neurosci 18:1265-71|
|Yamawaki, Naoki; Shepherd, Gordon M G (2015) Synaptic circuit organization of motor corticothalamic neurons. J Neurosci 35:2293-307|
|Harris, Kenneth D; Shepherd, Gordon M G (2015) The neocortical circuit: themes and variations. Nat Neurosci 18:170-81|
|Joshi, Ankur; Middleton, Jason W; Anderson, Charles T et al. (2015) Cell-specific activity-dependent fractionation of layer 2/3?5B excitatory signaling in mouse auditory cortex. J Neurosci 35:3112-23|
|Shepherd, Gordon M G (2014) Diversity and complexity in the pyramidal tract projectome. Nat Rev Neurosci 15:63|
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