Systems/Circuits Integrity of mGluR-LTD in the Associative/Commissural Inputs to CA3 Correlates with Successful Aging in Rats

The impact of aging on cognitive capabilities varies among individuals ranging from significant impairment to preservation of function on par with younger adults. Research on the neural basis for age-relatedmemory decline has focused primarily on the CA1 region of the hippocampus. However, recent studies in elderly human and rodents indicate that individual differences in cognitive aging are more strongly tied to functional alterations in CA3 circuits. To examine synaptic plasticity in the CA3 region, we used aged rats behaviorally characterized in ahippocampal-dependent task to evaluate the statusof long-termpotentiationand long-termdepression (LTPandLTD) in the associative/commissural pathway (A/C3CA3), which provides the majority of excitatory input to CA3 pyramidal neurons. We found that, unlike in CA1 synapses, in A/C3CA3 LTP is minimally affected by age. However, two forms of LTD, involving NMDA and metabotropic glutamate receptors (mGluR), are both greatly reduced in age-impaired rats. Age-unimpaired rats, in contrast, had intact mGluR LTD. These findings indicate that the integrity of mGluR-LTD at A/C3CA3 inputs may play a crucial role in maintaining the performance of CA3 circuitry in aging