Age-related changes in tonic activation of presynaptic versus extrasynaptic gamma-amniobutyric acid type B receptors in rat medial prefrontal cortex

作者：Carpenter Haley E; Kelly Kyle B; Bizon Jennifer L; Frazier Charles J^*

来源：Neurobiology of Aging, 2016, 45: 88-97.

DOI：10.1016/j.neurobiolaging.2016.05.015

• GABA(B)
• GABA(A)
• Prefrontal cortex
• Working memory
• L2/3 pyramidal neurons
• Age-related cognitive decline

The present study examined the effect of age on both glutamatergic and gamma-aminobutyric acid mediated (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 months) or aged (20-24 months) 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 extra-synaptic GABA(A) and GABA(B) receptors. These data demonstrate a shift in the site of GABA(B) receptor-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.

• 出版日期2016-9