METABOTROPIC GLUTAMATE-RECEPTOR MODULATION OF SYNAPTIC TRANSMISSION IN CORTICOSTRIATAL COCULTURES - ROLE OF CALCIUM INFLUX

Modulation of excitatory glutamatergic transmission at corticostriatal synapses by a metabotropic glutamate receptor (mCluR) was examined us ing a newly developed cell culture preparation in which small explants of cortical tissue are grown in co-culture with isolated striatal neu rons. Electrical stimulation of cortical tissue evoked excitatory post synaptic currents (eEPSCs) observed during tight-seal, whole-cell reco rdings from striatal neurons. Transmission was mediated by activation of AMPA/kainate-type glutamate receptors. The mGluR agonists, 1SR,3RS- ACPD and DCG-IV, reduced eEPSC amplitude. The effect of 1SR,3RS-ACPD i ncreased in a concentration-dependent manner. Application of phorbol d iacetate (PDAc) potentiated eEPSC amplitude and reduced the inhibitory effect of mGluR activation. Pretreatment with pertussis toxin (PTX) a lso reduced inhibition by 1SR,3RS-ACPD. Under conditions in which tran smission was independent of the function of voltage-gated calcium chan nels, mGluR activation reduced the frequency of occurrence of miniatur e EPSCs (mEPSCs), but did not alter mEPSC amplitude. This effect of mG luR activation was reduced by PDAc treatment. mGluR activation modulat es glutamatergic transmission via a presynaptic autoreceptor at cortic ostriatal synapses in this newly-developed corticostriatal co-culture preparation as in striatal slices. Modulation of transmission occurs w hether or not transmission involves activation of voltage-gated calciu m channels. Furthermore, many of the characteristics of mGluR modulati on of eEPSCs are shared by mGluR modulation of mEPSCs. These findings indicate that mechanisms downstream from calcium entry may contribute to modulation of synaptic transmission by mGluR autoreceptors.