Preferential reduction of synaptic efficacy in the dentate gyrus of hippocampal slices from aged rats during reduced glucose availability

•Electrophysiology in dentate gyrus of hippocampal slices from adult and aged rats during reduced glucose exposure.•Slices from aged animals showed exacerbated reduction in synaptic response, suggesting impaired glucose utilization.•This exacerbated reduction in synaptic activity was not due to a decreased capacity to produce action potentials.•Reduced DG glucose utilization and impaired peripheral glucose delivery may cause aging-related hippocampal dysfunction.

Glutamatergic synaptic activity entails a high energetic cost. During aging, a variety of neural metabolic changes have been reported that could compromise the capacity of neural circuits to maintain synaptic transmission during periods of reduced extracellular glucose. Indeed, a preferential compromise in evoked synaptic activity has been observed in hippocampal CA1 with age during exposure to low-glucose solutions. Whether this aging-related compromise in synaptic activity is regionally specific is unclear, however. Data suggest that the dentate gyrus (DG) preferentially exhibits hypometabolism with age and this region plays a critical role in spatial pattern separation, which is compromised with age. Therefore, we assessed whether synaptic activity is also preferentially affected in the DG with age. In vitro extracellular field potential recordings were used to monitor orthodromic and antidromic evoked activity in the DG granule cell layer in hippocampal slices from adult (8–12 months) and aged (22–27 months) rats in aCSF containing 10 mM glucose, followed by a reduced glucose aCSF containing 1 mM glucose. In 10 mM glucose-aCSF, orthodromic- and antidromic-evoked field potential activity was comparable between age groups. However, orthodromic-evoked population spike amplitude and field excitatory post-synaptic potential (EPSP) slope were preferentially decreased in slices from aged rats during exposure to 1 mM glucose-aCSF. Antidromic population spike amplitude was not differentially affected in slices from aged versus adult rats, however. These data suggest that synaptic efficacy is preferentially compromised with age under reduced glucose availability and, combined with a decreased capacity of the periphery to provide glucose to the central nervous system (CNS) during metabolically challenging conditions, could contribute to aging-related hippocampal dysfunction and cognitive decline.