CRCNS: Gamma Rhythms and Cell Assemblies

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DESCRIPTION (provided by applicant): Gamma frequency oscillations (30-90 Hz) are found in many parts of the nervous system, including the hippocampus, neocortex, entorhinal cortex and amygdala. They are believed to be important for a range of functions, including attention, early sensory processing, short term memory, motor activity. Mental illnesses, notably schizophrenia, are associated with pathologies in this rhythm, and many people are now studying these pathologies for clues to the pathophysiology of the diseases. At a simple level of description, gamma oscillations are thought to come about as interactions of parvalbumin positive (PV+) fast-spiking (FS) interneurons and pyramidal cells. However, it is known that other cell types, especially interneurons, participate in gamma rhythms and/or may modulate power and coherence of those rhythms. To understand the functional importance of these rhythms, it is necessary to better understand mechanisms that create and modulate them. Here we propose to use, for the first time, the combination of mathematical modeling with application of a set of emerging techniques involving molecular biology, optics, and electrophysiology to study the cell-type specific and circuitry properties of networks that produce gamma oscillations in the cortex. We will use in vitro models of the primary auditory cortex, with gamma oscillations induced using the glutamatergic agonist kainate or the cholinergic agonist carbachol. Specific classes of cells will be activated or suppressed by brief or longer periods of light. The work will focus on pyramidal cells, PV+ cells, cholecystokinin-expressing (CCK+) cells and somatostatin-containing (SOM+) interneurons. Minimal models will be constructed of these cells types and networks containing all of them. The model networks will be used to understand how the CCK+ and SOM+ interneurons interact with the PV+ cells to alter the gamma rhythms, in connection with experimental manipulations of the activity of different cell types. The experiments and models will also be used to understand how the CCK+ and SOM+ cells may affect the creation of cells assemblies. Broader Impacts: This work is part of a broader set of research by these labs on the importance of dynamics in cognitive function. The investigator is head of the Cognitive Rhythms Collaborative in the Boston area, a group of about 20 senior scientists, whose aim is to create and support new collaborations, including those making use of basic science and modeling in the study of disease, including Epilepsy, Parkinson's Disease, Autism and Schizophrenia. The work done in this project will provide new science that will interact with the work of many others in that group. The experimental work provides, for the first time, a combination of molecular biology, optics, and electrophysiology to study the cell-type specific and circuitry properties of networks; these techniques, pioneered by a member of this group, can then be used in many other contexts, beyond this group. The techniques and results will help provide information about the pathophysiology of mental illnesses; this has the potential of controlling such diseases by correcting the "oscillapathy" (defects in brain dynamics) associated with the symptoms. Finally, the specific project will also help train two graduate students and a postdoctoral fellow.