Nicotinic Acetylcholine Receptors in Sensory Cortex
Abstract
Acetylcholine release in sensory neocortex contributes to higher-order sensory function, in part by activating nicotinic acetylcholine receptors (nAChRs). Molecular studies have revealed a bewildering array of nAChR subtypes and cellular actions; however, there is some consensus emerging about the major nAChR subtypes and their functions in sensory cortex. This reviewfirst describes the systems-level effects of activating nAChRs in visual, somatosensory, and auditory cortex, and then describes, as far as possible, the underlying cellular and synaptic mechanisms. A related goal is to examine if sensory cortex can be considered a model system for cortex in general, because the use of sensory stimuli to activate neural circuits physiologically is helpful for understanding mechanisms of systems-level function and plasticity. A final goal is to highlight the emerging role of nAChRs in developing sensory cortex, and the adverse impact of early nicotine exposure on subsequent sensory–cognitive function.
Footnotes
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↵1 ACh activates two broad classes of receptors, namely, nicotinic and muscarinic receptors. Whereas this review focuses on nicotinic receptors, many studies have established the importance of muscarinic receptors in modulating sensory cortexfunction and plasticity (for reviews, see Weinberger and Bakin 1998; Edeline 1999; Rasmusson 2000; Metherate and Hsieh 2003).
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↵2 Permeability to Ca2+ is an important feature of some nAChRs, for example, presynaptic receptors whose activation results in increased neurotransmitter release (Wonnacott 1997), and α7 receptors may be even more permeable to Ca2+ than NMDA receptors (Seguela et al. 1993). Also, nAChR-associated increases in intracellular Ca2+ levels can result from the activation of voltage-dependent Ca2+ channels or release from intracellular stores (Zhang et al. 1994; Sharma and Vijayaraghavan 2003).
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↵3 Smoking tobacco increases levels of nicotine in the blood and brain (Isaac and Rand 1972; Henningfield et al. 1993). Although nicotine is considered the main psychoactive ingredient in tobacco, note that nicotine metabolites exert effects on the brain, as do other components of tobacco smoke (e.g., carbon monoxide), and that some consequences of nicotine administration may be indirect, for example, resulting from changes in brain blood flow or nicotine-induced release of neuromodulators or hormones (Benowitz 1996; Crooks and Dwoskin 1997; Domino et al. 2000; Ernst et al. 2001; Oncken and Kranzler 2003).
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↵4 Another form of sensory processing, “sensory gating,” involves α7 nAChR-mediated regulation of auditory processing in the hippocampus (Adler et al. 1998; Freedman et al. 2000). A sensory gating deficit has been observed in schizophrenics, and has been attributed to a genetic defect underlying impaired α7 nAChR function in hippocampal interneurons. Notably, this and other symptoms are transiently reversed by nicotine, a finding that may explain the very high rates (∼90%) of smoking among schizophrenics.
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↵5 Note that the anatomical work cited above derives from adult rats and cats, whereas most slice work is done in 2- to 3-week-old rodents (it is widely known among slice physiologists, though rarely mentioned in print, that whole-cell recordings become considerably more difficult in animals older than ∼3 wk). Thus, physiological results from slices may unwittingly reflect processes that occur only during postnatal development; such changes in nAChR function have become more apparent recently (see “nAChRs and Sensory Cortex Development” below).
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↵6 Transient appearance of α7 mRNA and αBTX binding also has been demonstrated in mouse somatosensory cortex, with a similar developmental time course and laminar distribution (Bina et al. 1995). However, these cortical markers are not accompanied by a corresponding expression in the thalamus, indicating a possible species difference.
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↵7 As mentioned above, most physiological studies on brain slices use tissue from young rodents (2 to 3 weeks old) for ease of recording. Although this is a relevant developmental period for the issues being considered here, the in vitro studies of nAChRs typically are not explicitly developmental, that is, the data are grouped together rather than split by age, and they bear unknown relationships to the age-related changes in cholinergic markers. Most of the results have been discussed above, and will not be repeated here unless clearly relevant to development.
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↵8 In most neurons, nicotine applied by itself did not produce a postsynaptic response, but instead modified the response to afferent stimulation (Aramakis and Metherate 1998). However, in a minority (<20%) of neurons, the first application of nicotine by itself produced a rapid, robust postsynaptic depolarization. This effect was difficult to study, because it required many minutes to recover from presumed nAChR desensitization, in contrast to the nicotinic enhancement of EPSPs, which recovered within seconds. Thus, the nature of the direct nicotine effect is unknown, but may involve postsynaptic nAChRs for which anatomical evidence was described above (Broide et al. 1996; Levy and Aoki 2002).
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Article and publication are at http://www.learnmem.org/cgi/doi/10.1101/lm.69904.
- Cold Spring Harbor Laboratory Press
