Modulation of afterpotentials and firing pattern in guinea pig CA3 neurones by group I metabotropic glutamate receptors.

Activation of group I metabotropic glutamate receptors (mGluRs) alters the firing patterns of individual CA3 pyramidal cells in guinea pig hippocampal slices. Following addition of the selective group I agonist (S)-3,5-dihydroxyphenylglycine (DHPG) to the bathing solution, pyramidal cells initially firing regular, single action potentials switched to firing in brief bursts. This change in firing pattern resulted from modulation by mGluRs of three afterpotentials. The medium and slow afterhyperpolarizations (m and sAHPs) were blocked by mGluR activation. In addition, a voltage-dependent after depolarization (ADP) was induced. Recordings from mutant mice lacking phospholipase C(beta1) (PLC(beta1)) showed that mGluR block of the mAHP, as well as induction of the ADP, depended on the phosphoinositide hydrolysis pathway. Block of the sAHP, however, was partly spared in the absence of PLC(beta1). Optical recordings of post spike intracellular Ca(2+) rises showed that mGluR block of the AHP was not mediated by alterations of action potential-associated Ca(2+) increases (Ca(2+) transients). The mGluR induction of an ADP was also independent of any changes in the Ca(2+) transient. The mGluR-induced change in the firing pattern of hippocampal pyramidal cells is thus the result of multiple mechanisms, including suppression of both m and sAHPs and activation of an ADP, that act together to produce a specific excitatory effect, namely an increased likelihood that a single action potential will lead immediately to one or more following action potentials.