Glutamatergic Synapses on Hippocampal Interneurons

Brown University, Providence RI

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Abstract

DESCRIPTION (provided by applicant): Excitatory synaptic transmission provides the basis of normal CNS function, and abnormalities of excitatory neurotransmission contribute to neurological and psychiatric disorders as wide-ranging as epilepsy, schizophrenia, and ischemia. Considerable progress has been made in understanding the processes that underlie normal excitatory synaptic transmission and synaptic plasticity at dendritic spine synapses between CA3 and CA1 pyramidal hippocampal neurons in the in vitro slice preparation. In this application, we propose to use electrophysiological recording to examine excitatory synapses made by the same afferents from CA3 pyramidal cells onto a different target population, GABAergic interneurons. These synapses have markedly different properties from those on their pyramidal cell neighbors. The interneurons are almost free of spines, so excitatory synapses are found nearly exclusively on dendritic shafts. Synapses on interneurons also are reported to lack the AMPAR subunit, GluR2. Furthermore, when high-frequency stimulation is delivered to CA3 afferents, synapses they make upon pyramidal cells undergo LTP; in contrast, our earlier work demonstrates that the same high-frequency stimulation to CA3 afferents triggers LTD at synapses onto interneurons. The fact that the same presynaptic afferents make synapses with distinct properties onto these two targets affords a unique opportunity to compare synaptic function, plasticity, and modulation in a defined and well-understood system in mature brain tissue. This work will provide insight into the proteins and signaling molecules required for regulation of normal synaptic transmission and plasticity at CNS excitatory synapses.