> Research overview

> Cell-specific circuits

> Mechanisms of Rett Syndrome

> Neurons and astrocytes

> Structural correlates of cortical plasticity

MIT

dendritic spine on a layer V pyramidal neuron GFP labeled neuron orientation map of rewired A1

Cortical Development, Plasticity and Dynamics

Cell-specific circuits

Distinct populations of neurons contribute to the development and function of neural circuits for vision; the precise organization of these cell populations and integration of their inputs within cortical area V1 is necessary for the establishment of coherent internal representations of visual stimuli. This project aims to explore the integrative properties of visual cortex on spatial scales ranging from individual dendrites to neural networks, identifying vectors of visual system dysfunction and targets for their intervention.

Distinct cell types in the visual cortex contribute in unique ways to cortical circuits and function. Furthermore, the location of cortical cells within maps enables them to have specific functions. We use state-of-the-art tools to examine the roles of specific cell types in visual cortex circuits in vivo. We are examining how neurons in ferret visual cortex simultaneously map multiple response features at single cell resolution, using two-photon imaging of calcium signals. We hypothesize that neuronal representations maximize continuity and coverage by creating precise representations of response features that contain spatially offset regions of high and low rates of change. We are also examining the response characteristics and mappings of neuronal populations which project to specific cortical targets. For this project, we use retrograde labeling of fluorescent tracers combined with two-photon imaging to compare response features and representations of neurons that project to area PSS, and hence to a putative motion-processing stream, with neurons that project to area 21, and hence to a putative form-processing stream. We also compare the responses of inhibitory neuron subpopulations in ferret V1 recorded with high-resolution imaging in vivo and subsequently identified by immunohistochemical markers ex vivo, and examine the hypothesis that specific inhibitory neuron subsets have distinct response features and tuning.

We are examining the response features of inhibitory neuron subpopulations in mouse V1 marked by a genetic cre-lox system in order to test our hypothesis that parvalbumin- and calretinin-expressing interneurons have distinct response properties. In mice with selective genetic deletion of one subpopulation or the other of these interneuron types, we are testing our prediction of particular influences on response features of excitatory neurons. At the cellular level, we are examining whether individual neuronal dendrites show integrative responses that are summed and thresholded at the soma to impart unique responses to neurons. We are focusing our efforts on response features of individual dendrites and dendritic compartments of single neurons in ferret V1 that have specific projections such as to area PSS and area 21. We examine their dendritic responses by labeling with either (a) intracellular injection of calcium indicator dye, or (b) a novel genetically engineered CaMKII FRET probe, and comparing responses to those at the soma recorded by visualized whole-cell patch recording. Together, we expect that these studies will contribute significantly to an understanding of how specific cell types in visual cortex contribute to cortical function, and thus how cortical dysfunction might arise from diseases that target a particular type of cell.