Local Glutamatergic and GABAergic Synaptic Circuits and Metabotropic Glutamate Receptors in the Hypothalamic Paraventricular and Supraoptic Nuclei

Abstract

Burst generation and synchronization in the hypothalamus is controlled by a combination of the intrinsic membrane conductances and the synaptic organization of the hypothalamic neurons. The projected synaptic inputs as well as the local synaptic organization of the cells play a crucial role in generating patterned electrical activity and synchronizing activity among individual cells of a given population of hypothalamic neurons. The majority of the synaptic inputs to the hypothalamic paraventricular (PVN) and supraoptic nuclei (SON) are mediated by glutamate and γ-aminobutyric acid (GABA)^1,2, and a substantial proportion of these inputs appear to derive from local sources^3,4,5. Given this, and the fact that the bursting patterns of neuroendocrine cells of the hypothalamus are sensitive to subtle changes in membrane potential and excitability, we hypothesize that local synaptic circuits in the hypothalamus and neuromodulatory inputs to hypothalamic neurons may be important for hypothalamic burst generation. To test these hypotheses, we studied the intrahypothalamic glutamatergic and GABAergic projections to neurons of the PVN and SON, and the neuromodulatory actions of glutamate via metabotropic glutamate receptors in these cells.