Modulation of synaptic transmission in the rat ventral septal area by the pharmacological activation of metabotropic glutamate receptors

The ventral septal area (VSA) is considered to be critically involved in th e control of the height and duration of fever. The major excitatory input t o this region of the brain is glutamatergic, and the aim of this study was to investigate possible modulation of this synapse by metabotropic glutamat e (mGlu) receptors. Whole-cell patch recordings were made from individual V SA neurons voltage-clamped at -60 mV. Activation of either group I or group II mGlu receptors (by bath application of 3,5-dihydroxyphenylglycine (DHPG ) or (2S,2'R,3'R)-2-(2',3'-dicarboxycyclopropyl)glycine (DCG-IV), respectiv ely) produced a long-lasting depression of synaptic transmission which in b oth cases was insensitive to the N-methyl-d-aspartate (NMDA) receptor antag onist D-2-amino-5-phosphonopentanoate (D-AP5). In contrast, application of (S)-2-amino-4-phosphonobutyric acid (L-AP4), a group III mGlu receptor agon ist, had a biphasic effect on synaptic transmission in the VSA, first elici ting a transient depression of transmission during drug application, follow ed by a marked and sustained potentiation of synaptic transmission upon dru g washout. The response elicited by L-AP4 was dependent on NMDA receptor ac tivation, as in the presence of D-AP5 the potentiation was replaced by an u nderlying long-term depression (LTD) of transmission. These data provide th e first evidence that metabotropic glutamate receptor agonists can induce b oth NMDA receptor-dependent and -independent modulation of synaptic transmi ssion in the VSA.