Synaptic circuit organization in mouse motor-frontal cortex

Local synaptic circuits in motor-frontal cortex engage in neural operations underlying many aspects of cognition and behavior – motor control, executive functions, working memory, and more – yet circuit organization at the synaptic, cellular, and molecular levels remains poorly understood in this agranular cortex. What is the functional organization of these synaptic pathways? What cellular and circuit-level operations do neurons in these perform? How do these local circuits communicate with each other and how do they interact with subcortical systems in the basal ganglia and thalamus? The focus of our laboratory is to apply multiple tools of quantitative synaptic circuit analysis to elucidate the functional ‘wiring diagrams’ of neocortical neurons in motor-frontal cortex. We use laser scanning photostimulation (LSPS) microscopy, based on glutamate uncaging and channelrhodopsin-2 excitation, for rapid functional mapping of synaptic pathways onto single neurons in brain slices of motor-frontal cortex. We are also applying a variety of circuit analysis tools in efforts to identify circuit-level mechanisms in mouse models of disease, including autism, Rett syndrome, epilepsy, and motor neuron diseases.

Software for laser scanning applications and electrophysiology: ScanImage and Ephus

Our lab is also involved in the development and maintenance of software tools for imaging and electrophysiology applications:

POST-DOCTORAL POSITIONS AVAILABLE to pursue studies of synaptic circuit organization in cortical and subcortical motor-frontal areas, in normal rodents and in mouse models of autism and neurological disease. Candidates with experience with quantitative methods in cellular electrophysiology and imaging are encouraged to apply. Send inquiries, with CV and list of references, to

Gordon MG Shepherd
Assistant Professor
MD, PhD Harvard University
Ward 7-233A
(312) 503-1342

Selected Publications:

Weiler N, Wood L, Yu J, Solla SA, Shepherd GMG (2008) Top-down laminar organization of the excitatory network in motor cortex. Nature Neuroscience 11:360-366

Wood L, Gray N, Zhou Z, Greenberg ME, Shepherd GMG (2009) Synaptic circuit abnormalities of MeCP2-deficient layer 2/3 pyramidal neurons in mouse motor-frontal cortex. Journal of Neuroscience 29:12440-12448

Anderson CT, Sheets PL, Kiritani T, Shepherd GMG (2010) Sublayer-specific microcircuits of corticospinal and corticostriatal neurons in motor cortex. Nature Neuroscience 13:739-744


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