INTRINSIC SYNAPTIC CIRCUITRY IN THE CEREBRAL CORTEX

University Of Maryland Baltimore, Baltimore MD

Investigators

Linked publications & trials

Abstract

The proposed research will investigate mechanisms that shape and modulate the response properties of cortical neurons. Key to understanding these mechanisms is the elucidation of both the physiological and morphological attributes of cortical neurons, and the synaptic interactions by which they form functional circuits. In addition, our recent findings suggest that the receptive fields of cortical neurons are dynamically regulated by patterns of sensory inputs. These studies focus on the barrel cortex, the region of the somatosensory cortex containing discrete representations of individual whiskers on rodents' snouts. The first aim is to test the hypothesis that the microcircuitry within individual barrels is sufficient for integration of inputs from multiple whiskers. Cortical neurons respond best to inputs from their principal whisker, and these responses are shaped principally by thalamocortical (TC) inputs. In contrast, there is controversy about the mechanisms that shape the responses to inputs from adjacent whiskers - the surround receptive field (SRF). One hypothesis states that SRFs are shaped entirely by intracortical interactions between barrels. The second hypothesis is that they are shaped entirely by synaptic interactions within an individual barrel. We will test these hypotheses with the use of functional imaging, whole-cell recordings, photostimulation, and neuroanatomical approaches, applied to in vitro slice preparations. The second aim is to test the hypothesis that corticothalamic (CT) neurons play a critical role in the initial stages of cortical processing. Anatomical considerations suggest that CT cells play a critical role in this process. In addition, CT cells are strategically placed to provide potent feed-forward inhibition to layer IV neurons. These postulates will be tested by determining the responses of CT neurons to TC inputs, and their postsynaptic influences on layer IV cells, in both in vivo and in vitro preparations. The third aim is to test the hypothesis that the receptive field properties of barrel cortex neurons are dynamically regulated by patterns of sensory inputs. The preceding aims address steady-state mechanisms involved in shaping receptive fields. Based on preliminary data we propose that SRFs are continually modulated by whisking frequency during exploratory behavior. We will test this hypothesis in vivo, and determine the mechanisms responsible for this dynamic regulation in vitro. The proposed studies will provide data pertinent to understanding the normal functions of the cerebral cortex and the processes underlying congenital or acquired neurological diseases resulting in sensory-motor deficits.