Local synaptic circuits in the frontal lobes engage in neural operations related to aspects of cognition and behavior such as motor control, executive functions, working memory, and more, yet the circuit organization at the synaptic, cellular, and molecular levels remains poorly understood for many of these neocortical areas. What is the functional organization of these synaptic pathways? What cellular and circuit-level operations do neurons in these circuits perform? How do these local circuits communicate with each other, and how do they functionally interact with subcortical systems in the basal ganglia and thalamus?

The focus of my research is to apply multiple tools of quantitative synaptic circuit analysis to understand the functional 'wiring diagrams' of neocortical neurons. We use laser scanning photostimulation (LSPS) microscopy as an electrophysiologically based in vitro imaging modality for rapid functional mapping of synaptic pathways onto single neurons in the frontal neocortex. In LSPS, one or more neurons are whole-cell recorded while small clusters of presynaptic neurons are excited at discrete locations to gauge the strength of inputs from those regions of the cortex. By stimulating hundreds of sites in a grid, an image of synaptic connectivity onto single neurons is generated. Complementary electrophysiological approaches include dual dendritic and somatic recordings, and paired recordings from two or more neurons, while complementary morphological approaches include quantitative 3D reconstructions of the axonal and dendritic components of these synaptic pathways. We are also applying these circuit analysis methods in efforts to identify 'circuitopathies' in mouse models of autism and other neurological diseases.

Gordon Shepherd
Assistant Professor
MD, PhD Harvard University
g-shepherd@northwestern.edu
Ward 7-233A
(312) 503-1342
 
 

Selected Publications:

Sternson SM, Shepherd GMG, Friedman JM. (2005) Topographic mapping of VMH-->arcuate nucleus microcircuits. Nature Neuroscience 8:1356-63.

Shepherd GMG, Svoboda K. (2005) Laminar and columnar organization of ascending excitatory projections to layer 2/3 pyramidal neurons in rat barrel cortex. Journal of Neuroscience 25:5670-5679.

Shepherd GMG, Stepanyants A, Bureau I, Chklovskii DB, Svoboda K. (2005) Geometric and functional organization of cortical circuits. Nature Neuroscience 8:782-790.

Holtmaat AJGD, Trachtenberg JY, Wilbrecht L, Shepherd GMG, Zhang X, Knott GW, Svoboda K. (2005) Turnover and stability of dendritic spines in the somatosensory and visual cortex in vivo. Neuron 45:279-291.

ZitoK, Knott G, Shepherd GMG, Shenolikar S, Svoboda K. (2004) Induction of spine growth and synapse formation by regulation of the spine actin cytoskeleton. Neuron 44:321-334.

Bureau I, Shepherd GMG, Svoboda K. (2004) Precise development of functional and anatomical columns in the neocortex. Neuron 42:789-801.

Shepherd GMG, Pologruto TA, Svoboda K. (2003) Circuit analysis of experience-dependent plasticity in the developing rat barrel cortex. Neuron 38:277-289.

Shepherd GMG, Raastad M. (2003) Axonal varicosity spacing: a new angle on cerebellar circuits. Cerebellum 2:110-113.

Raastad M, Shepherd GMG. (2003) Single-axon action potentials in the rat hippocampal cortex. Journal of Physiology 548:745-752.

Shepherd GMG, Raastad M, Andersen P. (2002) General and variable features of varicosity spacing along unmyelinated fibers of the hippocampus and cerebellum. Proceedings of the National Academy of Sciences USA 99:6340-6345.

 

 

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