This project will explore how inhibition is controlled in the dentate gyrus of the rat hippocampal slice. There are poorly understood disinhibitory mechanisms in the brain that transiently suppress inhibitory interneuron function. Setting the level of inhibitory neuron function has profound effects on neural plasticity such as long term potentiation, a model of learning, and on paroxysmal activity such as seizures. The dentate gyrus provides an excellent model system for the study of disinhibitory mechanisms because profound transient suppression of recurrent inhibition can be triggered in the dentate by a single conditioning stimulus to the adjacent alveus or stratum lucidum of the hippocampus. This phenomenon will herein be refered to as stimulus induced disinhibition or SID. Previous work in this laboratory has shown that GABAB receptor agonists disinhibit the dentate. The work proposed here will explore the hypothesis that SID in the dentate is due to GABAB mediated inhibition of inhibitory basket cells. In these experiments, recurrent inhibition is evoked in the dentate gyrus of the rat hippocampal slice by stimulation of the mossy fibers (granule cell axons). Inhibition is measured by its effect on the extracellular granule cell population spike triggered by a stimulus to the perforate path. SID is induced by stimulation of alveus or stratum recording methods will be used to study SID in the dentate.
The specific aims are to determine: 1) Whether other GABAB receptor antagonists will block SID and the long, late, presumably GABAB mediated inhibitory postsynaptic potentials in the dentate; 2) If inhibitory postsynaptic potentials in granule cells are suppressed during SID; 3) If SID facilitates long term potentiation of synaptic transmission in the dentate gyrus; 4) If basket cells are inhibited by GABAB inhibitory postsynaptic potentials during SID.
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