mGlu5 Acts As a Switch for Opposing Forms of Synaptic Plasticity at Mossy Fiber-CA3 and Commissural Associational-CA3 Synapses

Within the hippocampus, different kinds of spatial experience determine the direction of change of synaptic weights. Synaptic plasticity resulting from such experience may enable memory encoding. The CA3 region is very striking in this regard: due to the distinct molecular properties of the mossy fiber (MF) and associational–commissural (AC) synapses, it is believed that they enable working memory and pattern completion. The question arises, however, as to how information reaching these synapses results in differentiated encoding. Given its crucial role in enabling persistent synaptic plasticity in other hippocampal subfields, we speculated that the metabotropic glutamate receptor mGlu5 may regulate information encoding at MF and AC synapses. Here, we show that antagonism of mGlu5 inhibits LTP, but not LTD at MF synapses of freely behaving adult rats. Conversely, mGlu5 antagonism prevents LTD but not LTP at AC–CA3 synapses. This suggests that, under conditions in which mGlu5 is activated, LTP may be preferentially induced at MF synapses, whereas LTD is favored at AC synapses. To assess this possibility, we applied 50 Hz stimulation that should generate postsynaptic activity that corresponds to _m, the activation threshold that lies between LTP and LTD. MGlu5 activation had no effect on AC responses but potentiated MF synapses. These data suggest that mGlu5 serves as a switch that alters signal-to-noise ratios during information encoding in the CA3 region. This mechanism supports highly tuned and differentiated information storage in CA3 synapses.