Aging decreases rebound synaptic excitation produced by removal of NMDA receptor block in the striatum.

The influence of age on NMDA receptor-mediated excitatory postsynaptic potentials (EPSPs) was characterized in striatal in vitro brain slices using intracellular recording techniques. All slices were bathed in bicuculline methiodide (20 microM) to isolate EPSPs from intrinsic inhibition and Mg2+ was omitted from the artificial cerebral spinal fluid to reduce voltage-dependent fluctuations of NMDA receptor-mediated EPSPs. The NMDA receptor-mediated component of the EPSP was determined by comparing EPSP areas before and after block of NMDA receptors with 5-amino-phosphonovaleric acid (AP-5; 30 microM). No age difference was found in the percentage contribution of the NMDA receptor-mediated component of the EPSP, but an age difference was observed in the response to removal of AP-5. On average, washout of AP-5 produced a significant enhancement of the EPSP in young cells, while in aged cells the EPSP returned, on average, to the pre-AP-5 control level. These data demonstrate that NMDA receptors contribute equally to EPSPs at young and aged synapses and that age-related decreases in the number of NMDA receptors may be related to synapse loss. In addition, the response to removal of AP-5 suggests that functional properties of NMDA receptors may also be altered by aging.