Sprague-Dawley rats differ in responses to medial perforant path paired pulse and tetanic activation as a function of sex and age.

Abstract

Network plasticity in the medial perforant path (MPP) of adult (5-9 mo) and aged (18-20 mo) urethane-anesthetized male and female Sprague-Dawley rats was characterized. Paired pulses probed recurrent networks before and after a moderate tetanic protocol. Adult females exhibited greater EPSP-spike coupling suggesting greater intrinsic excitability than adult males. Aged rats did not differ in EPSP-spike coupling but aged females had larger spikes at high currents than males. Paired pulses suggested lower GABA-B inhibition in females. Absolute population spike measures were larger post-tetani in female rats than male rats. Relative population spike increases were greatest in adult males relative to females and to aged males. EPSP slope potentiation was detected with normalization in some post-tetanic intervals for all groups except aged males. Tetani shortened spike latency across groups. Tetani-associated NMDA-mediated burst depolarizations were larger for the first two trains in each tetanus in adult males than other groups. EPSP slopes over 30 min post-tetani predicted spike size in female rats, but not in males. Replicating newer evidence MPP plasticity in adult males was mediated by increased intrinsic excitability. Female MPP plasticity was related to synaptic drive increases, not excitability increases. Aged male rats were deficient in MPP plasticity.SIGNIFICANCE STATEMENTThe medial perforant path (MPP)-dentate gyrus (DG) granule cell synapse was the site of discovery of long-term potentiation in the mammalian nervous system but considering the current interest in sex and aging, surprisingly few studies have directly examined these variables in relation to tetanus-induced long-term and short-term (paired pulse) plasticity. Using an interleaved current-paired pulse interval protocol and moderate tetanic protocol young (5-9mo) and old (18-20mo) male and female urethane anesthetized rats were found to differ in levels of granule cell intrinsic excitability, E-S coupling, GABA-B inhibition, and tetanic NMDA current contributions to post-tetanic population spike potentiation. This study provides a platform or future examination of sex- and age-related changes in MPP-DG function.