Metabotropic glutamate receptors are involved in long-term potentiation in isolated slices of rat medial frontal cortex. R.M. Vickery, Shanida H. Morris & Lynn J. Bindman.. The Department of Physiology, University College London, Gower St. WC1E 6BT, UK.
APStracts 4:224N, 1997.
ABSTRACT
The prelimbic region of medial frontal cortex in the rat receives a direct input from the hippocampus, and this functional connection is essential for aspects of spatial memory. Activity-dependent changes in the effectiveness of synaptic transmission in the medial frontal cortex, namely long-term potentiation (LTP) and long-term depression (LTD) can persist for tens of minutes or hours, and may be the basis of learning and memory storage. Glutamatergic activation of ionotropic receptors is required to induce both LTP and LTD. We now present evidence of the involvement of metabotropic glutamate receptors in LTP in isolated slices of frontal cortex. Repetitive bursts of stimulation at theta frequencies (TBS) were applied to layer II, and monosynaptic EPSPs were monitored in layer V neurons of the prelimbic area. TBS was found to be more effective at inducing LTP than tetanic stimulation at 100 Hz, and produced LTP that lasted >30 min in 8 out of 14 neurons. Tetanic stimulation at 100 Hz in the presence of the N-methyl-D-aspartate (NMDA) antagonist 2-amino-5-phosphonopentanoate (AP5) had been reported to be a reliable method of inducing LTD in prelimbic cortex (Hirsch & Cr‚pel, 1991). However, we found this protocol did not facilitate the induction of LTD. The role of metabotropic glutamate receptors (mGluR) in LTP was assessed by using the selective, broad-spectrum antagonist (R,S)-à-methyl-4- carboxyphenylglycine (MCPG). This drug significantly reduced the incidence of LTP following TBS to only 1 of 14 neurones (p < 0.02, chi squared test). The pooled responses to TBS in MCPG showed significantly reduced potentiation (p < 0.02, ANOVA). The broad-spectrum mGluR agonist (1S,3R)-1-aminocyclopentane- 1,3-dicarboxylic acid (ACPD) and the selective group I agonist S-3 hydroxyphenylglycine (S-3HPG) both produced i) membrane depolarization, ii) an increase in number of spikes evoked by depolarizing current pulses, and iii) a reduction in the after-hyperpolarization. Similar effects we've produced by these agonists even when synaptic transmission was blocked by use of the GABAB receptor agonist, 200 æM baclofen, which suggests that group I mGluRs are present on layer V neurones. We conclude that mGluRs participate in the production of LTP in prelimbic cortex, and this excitatory effect could be mediated by the postsynaptic group I mGluRs. 

Received 29 May 1997; accepted in final form 2 September 1997.
APS Manuscript Number J447-7.
Article publication pending J. Neurophysiol.
ISSN 1080-4757 Copyright 1997 The American Physiological Society.
Published in APStracts on 7 October 1997