Interaction between Ampa-glutamate and Sst2-somatostatin Receptors in Rat Mediobasal Hypothalamus Requires Activation of Nmda And/or Metabotropic Glutamate Receptors and Depends on Intracellular

1 : SP and BP contributed equally to this work Running title : Interactions between AMPA glutamate and sst2 SRIF receptors Summary Modulation of glutamatergic transmission by neuropeptides is an essential aspect of neuronal network activity. Activation of the hypothalamic somatostatin sst2 receptor subtype by octreotide decreases AMPA glutamate responses, indicating a central link between a neurohormonal and neuromodulatory peptide and the main hypothalamic fast excitatory neurotransmitter. In mediobasal hypothalamic slices, sst2 activation inhibits the AMPA component of glutamatergic synaptic responses but is ineffective when AMPA currents are pharmacologically isolated. In mediobasal hypothalamic cultures, the decrease of AMPA currents induced by octreotide requires a concomitant activation of sst2 receptors with either NMDA and/or metabotropic glutamate receptors. This modulation depends on changes in intracellular calcium concentration induced by calcium flux through NMDA receptors or calcium release from intracellular stores following metabotropic glutamate receptor activation. These results highlight an unusual regulatory mechanism in which the simultaneous activation of at least three different types of receptors is necessary to allow somatostatin-induced modulation of fast synaptic glutamatergic transmission in the hypothalamus. Since the first demonstration of the depressant action of leucine-enkephalin on glutamate-evoked responses (Barker et al., 1978), interactions between neuropeptides and amino acids have turned out to be a major regulatory mechanism in the control of neuronal excitability and