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Department of Physiology and Pharmacology, SUNY Health Science Center at Brooklyn, Brooklyn, NY 11203, USA

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 afterdepolarization (ADP) was induced. Recordings from mutant mice lacking phospholipase C_ß1 (PLC_ß1) 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_ß1. Optical recordings of postspike intracellular Ca²⁺ rises showed that mGluR block of the AHP was not mediated by alterations of action potential-associated Ca²⁺ increases (Ca²⁺ transients). The mGluR induction of an ADP was also independent of any changes in the Ca²⁺ 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.

(Received 24 July 2003; accepted after revision 21 October 2003; first published online 24 October 2003)
Corresponding author S. R. Young: Department of Physiology and Pharmacology, SUNY Health Science Center at Brooklyn, Brooklyn, NY 11203, USA.  Email: steve.young{at}downstate.edu

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