Differential Effect of Aging on Synaptic Plasticity in the Ventral and Dorsal Striatum

Both the ventral and dorsal striatum are involved in various forms of motor, motivational and learning behaviors. Previously, we demonstrated that several striatum-dependent motor and learning behaviors were reduced in mice with increased age. In this study, we investigated the effects of aging on synaptic plasticity in brain slices containing the nucleus accumbens (NAc) or caudate-putamen (CPu), using electrophysiological recordings. We showed that long-term depression (LTD) was reduced or absent in the NAc of aged C57BL/6 mice, whereas the amount of LTD in the CPu of young and aged mice was similar. The LTD induced by 10-Hz stimulation is NMDAR-dependent in the NAc, but NMDAR-independent in the CPu. Our results suggest that NAc LTD may be more sensitive than CPu LTD to the effects of normal aging with a possibility that NMDAR-dependent LTD may be more susceptible to the aging process than non-NMDAR LTD. We also showed that paired-pulse facilitation was diminished in the NAc and CPu in aged mice, suggesting that aging is accompanied by significant decline in presynaptic function in both the ventral and dorsal striata. The age-related reduction in synaptic plasticity may be a cellular mechanism underlying the age-related impairments in striatum-dependent motor and cognitive functions.