Age related changes in tonic activation of presynaptic vs. extrasynaptic GABA _B receptors in rat medial prefrontal cortex

Abstract

The current study examined the effect of age on both glutamatergic and GABAergic signaling in the rodent medial prefrontal cortex (mPFC), with an emphasis on revealing novel changes contributing to increased inhibition in age. Whole-cell patch clamp recordings were obtained from layer 2/3 mPFC pyramidal neurons in acute cortical slices prepared from either young (4 month) or aged (20–24 month) male F344 rats. Results indicated that GABA _B receptors on GABAergic, but not on glutamatergic, inputs to layer 2/3 pyramidal cells are tonically activated by ambient GABA in young animals, and further demonstrated that this form of tonic inhibition is significantly attenuated in aged mPFC. Moreover, concurrent with loss of tonic presynaptic GABA _B autoreceptor activation, layer 2/3 pyramidal cells in aged mPFC are subjected to increased tonic activation of extrasynaptic GABA _A and GABA _B receptors. These data demonstrate a shift in the site of GABA _BR mediated inhibitory tone in the aged mPFC that clearly promotes increased inhibition of pyramidal cells in aged animals, and that may plausibly contribute to impaired executive function.