The Latest in Synaptic Transmission 395

POSTER 31

DIFFERENTIAL EFFECTS OF METABOTROPIC RECEPTOR ACTIVATION ON SYNAPTIC T R A N S M I S S I O N IN THE DENTATE GYRUS AND CA1 OF THE H IPPOCAMPUS IN VIVO. S~brin~ Davis and Seine Laroche. Laboratoire de Neurobiologie de I'Apprentissage et de la M~moire, CNRS URA 1491, Universite Paris-Sud, 91405 Orsay, France.

The metabotropic receptor consists of a family of seven subtypes that are directly linked with different second messenger systems. They have been shown to mediate a wide range of pharmacological and physiological responses. Recently, interest in this receptor has been stimulated by reports showing the agonist, ACPD, induces a slow onset potentiation of the evoked response in CA1 of the hippocampus (1), or induces a greater amount of LTP when tetanic stimulation is applied in the presence of ACPD (2). This effect, however, is somewhat controversial inasmuch as other reports have suggested that the agonist is capable of inducing depression of the response (3, 4) or potentiation of the response only when coupled with a subthreshold tetanus (5).

We have investigated the effects of metabotropic receptor (mGluR) activation on the perforant path evoked response in the dentate gyrus and the Schaffer collateral- commissural evoked response in CA1 in the urethane anaesthetised rat. In the dentate gyrus, ACPD (25 mM) injected icv (10 p.I at 0.25 ~l/min), induced an initial, short-lasting increase in the slope of the EPSP (5%) which peaked 10 min after the start of the injection, and then a long-lasting decrease in the response (15%; n=15) for a minimum of 90 min after the end of the injection. Delivery of a higher volume of ACPD (icv, 20 pl, 1.0 ~l/min) resulted in a greater decrease in the EPSP (24 %; n=4). High-frequency stimulation delivered 90 min after the end of injection resulted in PTP but not LTP.

We then tested the effect of ACPD on the evoked response in the presence of a higher concentration of Ca2+ (increased from 1.2 mM to 2.4 mM in the aCSF), infused locally in the dentate gyrus via a microdialysis probe, for 60 min before icv injections of ACPD (25 mM). High concentration of Ca2+ induced a slow onset potentiation of the EPSP (10%; n=14). Injections of ACPD induced an increase in the EPSP (30%; n=6) above that induced by Ca 2+ alone. It peaked approximately 20 min after the start of the injection of ACPD and remained elevated for at least 90 min. High-frequency stimulation induced a further increase in the slope of the EPSP, similar to that measured in the Ca2+ alone group (n=8).

In CA1, ACPD (25 mM, 10 I11 injected icv at 0.25 ~l/min) induced a small potentiation (10%; n=7) of the EPSP, which commenced almost immediately upon injection and continued for the duration of the recording period (210 min). Tetanic stimulation failed to induce further potentiation.

These data show, in the in vivo preparation, the metabotropic receptor agonist, ACPD induces depression of the evoked response in the dentate gyrus and potentiation of the response in CAl. These effects are probably mediated via different subtypes of the receptor. Increasing the levels of Ca2+ in the dentate gyrus prevents depression of the response and allows the induction of LTP, suggesting that levels of calcium may play a role in regulating activation of different subtypes of the metabotropic receptors upon activation by the agonist ACPD.

1. Bortolotto, Z.A. and Collingridge, G.L., 1993, Neuropharmacol., 32, 1-9. 2. McGuiness, N., et al., 1991, Eur. J. Pharmacol., 197, 231-232. 3. Pacelli, G.J. and Kelso, S.R., 1991, Neurosci. Lett., 132,267-269. 4. Musgrove, M.A., et al., 1993, Neuroreport, 4, 171-174. 5. Otani, S. and Ben-Ari, Y., 1991, Eur. J. Pharmacol., 205, 325-326.