AP5 blocks LTP in developing rat dentate gyrus and unmasks LTD

Abstract

The hippocampal dentate gyrus undergoes active neuronogenesis as well as growth and regression of neuronal elements and connections during the early postnatal period. In some brain regions, most notably in the visual system, both activity-dependent synaptic plasticity and NMDA receptor activation are candidate mechanisms by which neuronal architecture may be refined during brain maturation. To investigate whether similar mechanisms might obtain in developing dentate, we studied the effects of tetanic stimulation before and after NMDA receptor blockade in hippocampal slices from rats at 7–33 days. Field potentials were recorded in the suprapyramidal granule cell layer in response to stimulation of the medial perforant path. Robust long-term potentiation (LTP) of population spike amplitude (∼200% of baseline) was produced by a single tetanus (100 Hz, 2 s, 200 μs) at all ages studied. Application of 10 μ M AP5 depressed population spike amplitude only in the younger slices (∼81% of baseline at 8–15 days; ∼86% of baseline at 16–24 days), suggesting that the NMDA receptor-mediated component of normal synaptic transmission is higher in early development and decreases with maturation. AP5 prevented or significantly diminished LTP at all ages, establishing the NMDA dependence of LTP induction 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 receptor-mediated activity and the capacity for bidirectional synaptic plasticity are characteristic of immature dentate. These processes may influence dentate morphogenesis by contributing to the growth, regression, and stabilization of neuronal elements.