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bioRxiv · 10.1101/2021.04.13.439708

α3β4* Nicotinic acetylcholine receptors strongly modulate the excitability of VIP neurons in the mouse inferior colliculus

Rivera-Perez, L. M.·Kwapiszewski, J. T.·Roberts, M. T.
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Abstract

The inferior colliculus (IC), the midbrain hub of the central auditory system, receives extensive cholinergic input from the pontomesencephalic tegmentum. Activation of nicotinic acetylcholine receptors (nAChRs) in the IC can alter acoustic processing and enhance auditory task performance. However, how nAChRs affect the excitability of specific classes of IC neurons remains unknown. Recently, we identified vasoactive intestinal peptide (VIP) neurons as a distinct class of glutamatergic principal neurons in the IC. Here, in experiments using male and female mice, we show that cholinergic terminals are routinely located adjacent to the somas and dendrites of VIP neurons. Using whole-cell electrophysiology in brain slices, we found that acetylcholine drives surprisingly strong and long-lasting excitation and inward currents in VIP neurons. This excitation was unaffected by the muscarinic receptor antagonist atropine. Application of nAChR antagonists revealed that acetylcholine excites VIP neurons mainly via activation of 3{beta}4* nAChRs, a nAChR subtype that is rare in the brain. Furthermore, we show that cholinergic excitation is intrinsic to VIP neurons and does not require activation of presynaptic inputs. Lastly, we found that low frequency trains of acetylcholine puffs elicited temporal summation in VIP neurons, suggesting that in vivo-like patterns of cholinergic input can reshape activity for prolonged periods. These results reveal the first cellular mechanisms of nAChR regulation in the IC, identify a functional role for 3{beta}4* nAChRs in the auditory system, and suggest that cholinergic input can potently influence auditory processing by increasing excitability in VIP neurons and their postsynaptic targets. Key points summaryO_LIThe inferior colliculus (IC), the midbrain hub of the central auditory system, receives extensive cholinergic input and expresses a variety of nicotinic acetylcholine receptor (nAChR) subunits. C_LIO_LIIn vivo activation of nAChRs alters the input-output functions of IC neurons and influences performance in auditory tasks. However, how nAChR activation affects the excitability of specific IC neuron classes remains unknown. C_LIO_LIHere we show in mice that cholinergic terminals are located adjacent to the somas and dendrites of VIP neurons, a class of IC principal neurons. C_LIO_LIWe find that acetylcholine elicits surprisingly strong, long-lasting excitation of VIP neurons and this is mediated mainly through activation of 3{beta}4* nAChRs, a subtype that is rare in the brain. C_LIO_LIOur data identify a role for 3{beta}4* nAChRs in the central auditory pathway and reveal a mechanism by which cholinergic input can influence auditory processing in the IC and the postsynaptic targets of VIP neurons. C_LI

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Rivera-Perez, L. M., Kwapiszewski, J. T., Roberts, M. T.. 2021-04-14. α3β4* Nicotinic acetylcholine receptors strongly modulate the excitability of VIP neurons in the mouse inferior colliculus. https://doi.org/10.1101/2021.04.13.439708

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