AP5 BLOCKS LTP IN DEVELOPING RAT DENTATE GYRUS AND UNMASKS LTD

The hippocampal dentate gyrus undergoes active neuronogenesis as well as growth and regression of neuronal elements and connections during t he early postnatal period. In some brain regions, most notably in the visual system, both activity-dependent synaptic plasticity and NMDA re ceptor activation are candidate mechanisms by which neuronal architect ure may be refined during brain maturation. To investigate whether sim ilar mechanisms might obtain in developing dentate, we studied the eff ects of tetanic stimulation before and after NMDA receptor blockade in hippocampal slices from rats at 7-33 days. Field potentials were reco rded in the suprapyramidal granule cell layer in response to stimulati on of the medial perforant path. Robust long-term potentiation (LTP) o f population spike amplitude (similar to 200% of baseline) was produce d by a single tetanus (100 Hz, 2 s, 200 mu s) at all ages studied. App lication of 10 mu M AP5 depressed population spike amplitude only in t he younger slices (similar to 81% of baseline at 8-15 days; similar to 86% of baseline at 16-24 days), suggesting that the NMDA receptor-med iated component of normal synaptic transmission is higher in early dev elopment and decreases with maturation. AP5 prevented or significantly diminished LTP at all ages, establishing the NMDA dependence of LTP i nduction in the medial perforant path throughout development. AP5 also unmasked tetanus-induced homosynaptic long-term depression (62-75% of baseline) in the younger slices (8-24 days). Thus, prominent NMDA rec eptor-mediated activity and the capacity for bidirectional synaptic pl asticity are characteristic of immature dentate. These processes may i nfluence dentate morphogenesis by contributing to the growth, regressi on, and stabilization of neuronal elements. (C) 1995 Academic Press, I nc.