Group I mGluR Agonist DHPG Facilitates the Induction of LTP in Rat Prelimbic Cortex In Vitro

Long-term potentiation (LTP) of synaptic transmission is a favored neural model for learning and memory. In isolated slices of rat prelimbic cortex, glutamatergic activation of metabotropic receptors (mGluRs) is required for the production of LTP at synapses on layer V neurons. Group I mGluRs are found in neocortex, and in prelimbic cortex they have been located on layer V neurons. We have now investigated whether application of the selective group I mGluR agonist, (S)-3,5-dihydroxyphenylglycine (DHPG) facilitates the induction of LTP. We recorded field potentials in layer V in response to test shocks applied to layer II and measured the population spike peak amplitude and slope. Intracellular recording was used to examine the correspondence between excitatory postsynaptic potentials (EPSPs) and action potentials with components of the field potential, and to further investigate the action of DHPG. Repetitive bursts of stimulation at theta frequencies (TBS) did not consistently alter the magnitude or slope of the population spike (mean response 105 ± 4%, mean ± SE of control at 30 min after TBS ended, n = 9 slices, no significant difference). When DHPG was added to the bathing medium for 10 min during continued test stimulation, the slope and amplitude of the population spike were significantly reduced, but 30 min after wash out of the DHPG, they recovered (mean response 89 ± 10% of control, n = 6 slices, no significant difference). However, when TBS was administered in conjunction with bath application of DHPG, LTP of the population spike was induced (mean response 147 ± 12% of control at 30 min after TBS ended, P = 0.004, paired t -test, n = 9 slices). We conclude that co-application of DHPG with TBS facilitates the induction of LTP of the population spike, which supports a role for group I mGluRs in the activity-dependent induction of LTP in the prelimbic cortex.