Metabotropic Glutamate Receptors in Median Preoptic Neurons Modulate Neuronal Excitability and Glutamatergic and GABAergic Inputs From the Subfornical Organ

Abstract

Cardiovascular and behavioral responses to circulating angiotensin require intact connectivity along the upper lamina terminalis joining the subfornical organ (SFO) with the median preoptic nucleus (MnPO). In the present study on MnPO neurons, we used whole cell patch-clamp recording techniques in brain slice preparations to evaluate the influence of metabotropic glutamate receptor (mGluR) agonists on modulating their intrinsic excitability and SFO-evoked glutamatergic and GABAergic postsynaptic currents. In 22/36 cells, bath application of a mGluR group I agonist ( S)-3,5-dihydroxyphenylglycine (DHPG) induced a TTX-resistant inward current coupled with decrease in a membrane K+ conductance but also a possible increase in a nonselective cationic conductance. By contrast, 27/49 cells responded to a mGluR group II agonist (2S,2′R,3′R)-2-(2′,3′-dicarboxycyclopropyl)glycine (DCG IV) with a TTX-resistant outward current and increase in membrane conductance that reversed around −95 mV, suggesting opening of K+ channels. None of 19 cells responded to the mGluR group III agonist l-(+)-2-amino-4-phosphonobutyric acid (l-AP4). Agonists for all mGluR groups suppressed SFO-evoked excitatory postsynaptic currents and significantly increased paired-pulse ratios, implying a presynaptic mechanism. Only the mGluR group II agonist significantly reduced SFO-evoked inhibitory postsynaptic currents and caused an increase in paired-pulse ratios. These results suggest a complexity of pre- and postsynaptic mGluRs are available to modulate rapid neurotransmission along the upper lamina terminalis from SFO to MnPO.