Impact of aging on postsynaptic neuronal nicotinic neurotransmission in auditory Thalamus

Abstract

The flow of auditory information through the medial geniculate body (MGB) is regulated, in part, by cholinergic projections from the pontomesencephalic tegmentum (PMT). The functional significance of these projections is not fully established, but they have been strongly implicated in the allocation of auditory attention. Using in vitro slice recordings, we have analysed postsynaptic function and pharmacology of neuronal nicotinic acetylcholine receptors (nAChRs) in young adult and aged rat MGB. We find that acetylcholine produces significant excitatory postsynaptic actions on young MGB neurons, likely mediated by β2-containing heteromeric nAChRs. Radioligand binding studies show a significant age-related loss of heteromeric nAChR receptor number which supports patch-clamp data showing an age-related loss in acetylcholine efficacy in evoking postsynaptic responses. Use of the β2-selective nAChR antagonist, dihydro-β-erythroidine, suggests that loss of cholinergic efficacy may also be due to an age-related subunit switch from high affinity β2-containing nAChRs to low affinity β4–containing nAChRs, in addition to the aforementioned loss of total nAChR number. This age-related nAChR dysfunction may partially underpin the attentional deficits which contribute to the loss of speech understanding in the elderly.

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