Coincident activation of mGluRs and mAChRs imposes theta frequency patterning on synchronised network activity in the hippocampal CA3 region

Activation of metabotropic glutamate receptors (mGluRs) with the broad spec trum mGluR agonist 1S,3R ACPD (10-50 mu M) induced spontaneous field potent ials at low frequencies ('burst-mode' activity <1 Hz) in the CA3 region of rat hippocampal slices. At higher concentrations (100-400 mu M) ACPD switch ed this form of activity to a second, more complex pattern of activity in w hich intermittent episodes of theta frequency oscillations predominated ('t heta-mode' activity; 4-14 Hz). Both patterns of activity were evoked by sel ective activation of group I mGluRs and, in particular, could be induced by activation of mGluR5 alone using the subtype selective agonist CHPG (0.5-5 mM). In contrast, activation of group II mGluRs (DCG IV; 100 mu M) produce d only burst-mode behaviour whilst activation of group III mGluRs (L-AP4; 1 00 mu M) did not result in synchronised network activity. Concurrent extra- and intracellular recordings demonstrated that this mGluR-induced theta-mo de activity represented the synchronous firing of CA3 pyramidal cells and t hat it shared a similar temporal signature to that generated by activation of muscarinic acetylcholine receptors (mAChRs). Furthermore, application of mGluR and mAChR agonists at concentrations sufficient to produce only burs t-mode activity when applied individually, produced theta-mode activity whe n co-applied. These data suggest that the level of activation of different mGluRs and mAChRs crucially determine the pattern of rhythmical network act ivity generated in the hippocampal CA3 network. These results also indicate that individual receptor subtypes (i.e. mGluR5) can initiate patterns of c oherent network activity but that interactions between the cholinergic and glutamatergic transmitter systems may also be important factors in governin g the temporal patterning of hippocampal network activity. (C) 2000 Elsevie r Science Ltd. All rights reserved.