Neural Circuits and the Coordination of Neuronal Activity

One of the critical issues in the field of neuroscience is to determine how different regions of the brain interact with each other to mediate perception, cognition, and a variety of other neurological functions. In addition, many neurological disorders are produced by biochemical or morphological lesions that alter processing in one brain region and disrupt the transmission of information to successive levels of the nervous system. To address these issues, experiments in our laboratory are concerned with determining how neuronal responses in one brain region affect processing in other anatomically-connected regions of the nervous system.

We use a variety of anatomical, computational, electrophysiological, and neurochemical approaches to investigate these issues. Our laboratory has been instrumental in refining the use of cross-correlation analysis to characterize neuronal interactions between several different brain regions. This technique involves using mathematical algorithms to analyze the relative timing of extracellular discharges recorded simultaneously from multiple neurons. The results of this analysis allow us to quantify the strength of synaptic connections between pairs of neurons and to characterize the precise nature of these interactions. Ultimately this information is used to make inferences about the anatomical connections in the underlying neural circuits and to determine the rules that govern their dynamic operation.

A major goal in our laboratory is to understand how sensory information is transmitted from the periphery through subcortical relay centers and then to multiple areas of the cerebral cortex. As part of this goal we have characterized interactions between neurons at different levels of the neuraxis including the brainstem, thalamus, and neocortex of the somatosensory system. Our results indicate a significant decline in the efficacy of neurotransmission as sensory signals progress from the periphery to higher levels of the neuraxis. Once a sensory signal reaches the neocortex, information is transmitted by a combination of parallel and serial routes to the different layers of each cortical column. We are currently analyzing thalamocortical and corticocortial interactions to determine if synchronous activity is a basic coding strategy used by sensory networks to recognize stimulus features that vary continuously in the spatial and/or temporal domain.

Another research focus in our laboratory involves the analysis of neuronal activity in the neostriatum and related brain regions. Neostriatal circuits are poorly understood despite the intensive research effort that has followed the discovery that Parkinson's disease, Huntington's chorea, schizophrenia, and other psychomotor disorders are caused, in part, by dysfunctional circuits in this brain region. Sensory and motor regions of the cerebral cortex send prominent projections to the neostriatum and we are characterizing the anatomical pattern of those connections and examining their role in coordinating neostriatal activity. We also plan to characterize neuronal interactions within the neostriatum as a function of their location in specific neurochemically-defined neostriatal compartments and to determine how different classes of psychotherapeutic drugs alter the coordination of neostriatal activity.