Cholinergic receptors: dual roles in transduction and plasticity

doi:10.1016/S0378-5955(00)00124-6

Hearing Research

Volume 147, Issues 1–2, September 2000, Pages 104-112

https://doi.org/10.1016/S0378-5955(00)00124-6 Get rights and content

Abstract

The regional distributions and possible functions of nicotinic acetylcholine receptors (nAChRs) in the developing and adult auditory rat brain are reviewed. The predominant nAChR in the auditory brainstem is the α7 homomeric receptor. α7 mRNA and protein are expressed in selected regions of the cochlear nucleus (CN), inferior colliculus (IC), medial superior olive, lateral superior olive, ventral nucleus of the lateral lemniscus and superior paraolivary nucleus. Peak expression of mRNA and protein occurs by the second postnatal week in most auditory brainstem areas. In contrast, the α3 and β4 nicotinic subunits are expressed in the embryo and early in postnatal development in the CN and IC, but not other brainstem nuclei. Of particular interest is the octopus cell region of the posteroventral cochlear nucleus (PVCN). α3 and β4 are down-regulated in the octopus cell region about postnatal day 10, which is the age that α7 is at peak expression. NAChRs play important roles in transduction and in regulating intracellular calcium. The ability of the α7 receptor to synchronize synaptic activity and stabilize synapses makes it a prime candidate as a mechanism underlying homeostatic plasticity in the auditory system.

Introduction

Cholinergic synapses have been identified in auditory brainstem nuclei using a variety of techniques, including the immunocytochemical labeling of choline acetyltransferase (ChAT) (Henderson and Sherriff, 1991, Vetter et al., 1993, Yao and Godfrey, 1995, Yao and Godfrey, 1997), the vesicular acetylcholine transporter (VAChT) (Yao and Godfrey, 1999a), muscarinic receptors (Yao and Godfrey, 1995, Yao and Godfrey, 1997) and the nicotinic α7 receptor (Yao and Godfrey, 1999b), the autoradiographic labeling of cholinergic receptor ligands (Segal et al., 1978, Arimatsu et al., 1981, Yao et al., 1996, Yao and Godfrey, 1997, Happe and Morley, 1998), the identification of the α7 nicotinic receptor with in situ hybridization (Happe and Morley, 1998, Morley, 1997), biochemical measurements of ChAT and acetylcholinesterase (AChE) (Godfrey et al., 1987a, Godfrey et al., 1987b, 1990), and the labeling of neurons and axons by AChE histochemistry (Frostholm and Rotter, 1986, Osen and Roth, 1969, McDonald and Rasmussen, 1971, Osen et al., 1984, Yao and Godfrey, 1995, Yao and Godfrey, 1997).

The most studied cholinergic pathway in the auditory system is the olivocochlear bundle (OCB). Collaterals to the cochlear nucleus (CN) arise from the OCB and are one source of cholinergic synapses in the rat CN, but the main source of cholinergic axons projecting to the CN originate from small ChAT-positive (non-olivocochlear) neurons in the VNTB (Sherriff and Henderson, 1994).

Section snippets

Nicotinic receptors in the auditory brainstem

The nicotinic subunits in the cochlea include α9 (Morley et al., 1998) and α10 (Boulter, personal communication) in hair cells and α6, α7, and β2 in spiral ganglion neurons (Morley et al., 1998). The predominant subunits expressed in the cochlea (α9 and α6) are not expressed in the CN, indicating that the receptors mediating responses to the OCB collaterals are not the same as those in OHCs or the dendrites of spiral ganglion neurons.

Muscarinic and nicotinic cholinergic receptors have

The dual role of nicotinic receptors

Nicotinic receptors have a dual role in the central nervous system. First, they serve as neurotransmitter receptors in transduction. The well-characterized nicotinic receptor in skeletal muscle are a well-established model for studying transmitter-gated membrane channels, receptor gene expression and gene regulation during development (reviewed in Salpeter and Loring, 1985, Burden, 1998). Neuronal type nAChRs have been identified in peripheral ganglia (e.g. Conroy and Berg, 1995, Mandelzys et

Developmental regulation of nAChRs

During various stages of development, neurons may express nAChRs with different electrophysiological properties and calcium permeabilities than those of the adult. These differing properties of nAChRs suggest that the actions of ACh regulate age-specific cellular processes, such as differentiation, synapse maturation and maintenance, and experience-dependent synaptic plasticity.

In this laboratory, we have recently focused on nicotinic subunit mRNA expression and receptor binding in the rat

Function of nicotinic receptors

The heavy expression of α7 in several discrete areas of the auditory brainstem suggests that α7 could play an important role in an excitatory feedback system. Many of the areas labeled by α7 and ¹²⁵I-α-BuTX binding, including the octopus cells, are involved in processing monaural rather than binaural sound information.

The α7 receptor demonstrates all the hallmark characteristics of a nicotinic receptor. It is an inwardly rectifying (Forster and Bertrand, 1995, Bonfante-Cabarcas et al., 1996),

Homeostatic plasticity

The properties of nicotinic receptors (calcium permeability, rapid desensitization) make them especially well-suited as candidates for involvement in homeostatic plasticity. In contrast to Hebbian plasticity, the mechanisms acting in homeostatic plasticity stabilize the properties of neural circuits (Turrigiano, 1998). Hebb proposed that at the time an action potential in one neuron generates an action potential in a second (post-synaptic) neuron, the strength of the synapse is increased,

Acknowledgements

The authors thank Dr. W. Bruce Warr for his assistance in identifying auditory brainstem nuclei in their preparations. The authors also thank Theresa Holderread for her fine technical expertise and Skip Kennedy for preparing the figures. This research was supported, in part, by NIH Grant DC00215.

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Cholinergic receptors: dual roles in transduction and plasticity

Abstract

Introduction

Section snippets

Nicotinic receptors in the auditory brainstem

The dual role of nicotinic receptors

Developmental regulation of nAChRs

Function of nicotinic receptors

Homeostatic plasticity

Acknowledgements

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Neurosci. Lett.

Hear. Res.

Curr. Opin. Neurobiol.

Properties of neuronal nicotinic acetylcholine receptors: pharmacological characterization and modulation of synaptic function

J. Pharmacol. Exp. Ther.

Nicotine selectively enhances NMDA receptor-mediated synaptic transmission during postnatal development in sensory neocortex

J. Neurosci.

An atlas of α-bungarotoxin binding sites and structures containing acetylcholinesterase in the mouse central nervous sytem

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Mot. Res.

Developmental changes in the nicotinic response of ciliary ganglion neurons

J. Neurophysiol.

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Genes Dev.