In this program project application, a group of three independent faculty at the same institution, UCLA, have combined expertise in electrophysiology, neuroanatomy, biochemistry, and molecular biology to approach important questions in basic neurobiology which would be difficult for any one individual. The them chosen for collaborative research is """"""""Plasticity of GABA Receptors"""""""". Program Director Richard Olsen has assembled, like the structure of GABA/A receptors themselves, a """"""""heterooligomer"""""""" of scientists. Olsen's component project is 'Benzodiazepine-induced GABA/A receptor plasticity'. Carolyn Houser's project is 'Plasticity of GABA/A receptor subunit localization', and involves the kindling model of chronic epilepsy in rats. All projects focus on GABA/A receptors, the major postsynaptic receptors involved in rapid inhibitory neurotransmission. These receptors, and 'plastic' alterations in them that occur in response to a variety of extraordinary experiences, are implicated in many neurological and psychiatric disorders. The wide variety of employed techniques promises a level of investigation aimed at understanding the assembly, functioning, and plasticity of GABA/A receptors in the mammalian nervous system. It is both hoped and expected that the proposed studies will serve as a leading inquisitive collaboration to unveil the short and long-term control of inhibition in the mammalian brain. The proposed studies deal with the nature of the alterations in the molecular structure and function of GABA/A receptors that contribute to chronic changes in excitability of neurons or to the mechanism of tolerance and withdrawal from chronic drug exposure. Ultimately, therapeutic strategies could be based on our studied, aimed rationally at preventing the unwanted or pathological alterations in GABA/A receptors characteristic of several neurological and psychiatric disorders.
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