Pre‐ and postsynaptic contributions to age‐related alterations in corticostriatal synaptic plasticity

Aging creates deficits in motor performance related to changes in striatal processing of cortical information. This study describes age‐related changes in corticostriatal snaptic plasticity and associated mechanisms, which may contribute to declines in motor behavior. Intracellular recordings revealed an age‐related decrease in the expression of paired‐pulse, posttetanic, and long‐term potentiation (LTP). The age‐related difference in LTP was associated with reduced sensitivity to block of N‐methyl‐D‐aspartate (NMDA) receptors in the aged population. These age‐related changes could not be explained by increased L‐type Ca2+channel activity, since block of L‐type Ca2+ channels with nifedipine increased rather than decreased the age‐related difference in long‐term plasticity. Age‐related increases in reactive oxygen species (ROS) modulation were also ruled out, since application of H2O2 produced changes in synaptic function that were opposite to trends seen in aging, and addition of the antioxidant Trolox‐C had a larger effect on long‐term plasticity in young rats than in older rats. A robust age‐related difference in long‐term synaptic plasticity was found by studying synaptic plasticity following the blocking of D2 receptors with l‐sulpiride, which may involve age‐difference in NMDA receptor function. l‐sulpiride consistently enabled a slow development of LTP at young (but not aged) corticostriatal synapses. However, No age differences were found in the sensitivity to the addition of the D2 receptor agonist quinpirole. These findings provide evidence for age‐induced changes in the release properties of cortical terminals and in the functioning of postsynaptic striatal NMDA receptors, which may contribute to age‐related deficits in striatum control of movement. Synapse 60:223–238, 2006. © 2006 Wiley‐Liss, Inc.

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