Muscarinic receptors at the auditory thalamocortical circuits and relevance to hearing

The auditory thalamus and cortex are the critical structures in the auditory hierarchy, owing to their crucial role in plasticity, auditory object formation, speech understanding, and spatiotemporal integration. Acetylcholine, a key neuromodulator, alters the abovementioned processes by orchestrating its effects with other neurotransmitters and its high-affinity receptor, the muscarinic receptor. This manuscript extensively covers the localization and function of different muscarinic receptors in the auditory thalamocortical system. Gaps in research of muscarinic localization and function are identified in hearing function. Also, a scarcity of studies examining muscarinic structure and function with tinnitus and hearing loss (age-related/noise-induced) is presented. Central changes in neurotransmitter receptors and auditory coding occur due to maladaptive plasticity in hearing loss and tinnitus and alter auditory object formation and spatiotemporal discrimination behaviors. Addressing these gaps are key to developing therapeutic strategies for hearing loss and tinnitus, apart from rectifying cochlear insult that led to hearing loss/tinnitus. Focusing on the muscarinic receptors is important owing to their abundance and demonstrated functional role in the auditory thalamocortical circuits and cortical development in mutant mice. In conclusion, this review emphasizes the need to answer questions on the localization and function of muscarinic receptors.