Xanomeline restores endogenous nicotinic acetylcholine receptor signaling in mouse prefrontal cortex.

ABSTRACT: Cholinergic synapses in prefrontal cortex are vital for attention, but this modulatory system undergoes substantial pre- and post-synaptic alterations during adulthood. To examine the integrated impact of these changes, we optophysiologically probe cholinergic synapses ex vivo, revealing a clear decline in neurotransmission in middle adulthood. Pharmacological dissection of synaptic components reveals a selective reduction in postsynaptic nicotinic receptor currents. Other components of cholinergic synapses appear stable, by contrast, including acetylcholine autoinhibition, metabolism, and excitation of postsynaptic muscarinic receptors. Pursuing strategies to strengthen cholinergic neurotransmission, we find that positive allosteric modulation of nicotinic receptors with NS9283 is effecti

SUBMITTER: Power SK 

PROVIDER: S-EPMC9938126 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature