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Regulation of excitation and inhibition balance in C. elegans

  • Author(s): Stawicki, Tamara M.
  • et al.
Abstract

Proper neurological function requires a regulated balance of excitation and inhibition in the nervous system. An imbalance of these two forms of neuronal transmission is a hallmark of the neurological disorder, epilepsy. In this dissertation I describe my work on a C. elegans model mimicking the neurological condition of epilepsy. A gain of function mutation in the acetylcholine receptor subunit gene, acr-2, causes increased cholinergic excitation and decreased GABAergic inhibition, resulting in whole body convulsions. Through screening for genetic suppressors of this mutant the composition of the ACR-2 receptor was determined. Further studies of a unique genetic suppressor identified a key role for TRPM channels and systemic ion homeostasis in the control of excitation and inhibition imbalance. Lastly, I found that the cholinergic motor neurons use neuropeptides to alleviate the severity of convulsions caused by the acr-2(gf) mutation. My thesis work identifies a new model for studying excitation and inhibition balance in vivo. While traditional work on neuronal network balance has focused on fast excitatory or inhibitory transmitter systems my work highlights the role of nonneuronal and neuromodulatory regulation of this balance

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