Nicotinic modulation of tone-evoked responses in auditory cortex reflects the strength of prior auditory learning

Abstract

Nicotinic acetylcholine receptors (nAChRs) contribute to sensory-cognitive function, as demonstrated by evidence that nAChR activation enhances, and nAChR blockade impairs, neural processing of sensory stimuli and sensory-cognitive behavior. To better understand the relationship between nAChR function and behavior, here we compare the strength of nAChR-mediated physiology in individual animals to their prior auditory behavioral performance. Adult rats were trained on an auditory-cued, active avoidance task over 4 days and classified as "good," "intermediate" or "poor" performers based on their initial rate of learning and eventual level of performance. Animals were then anesthetized, and tone-evoked local field potentials (LFPs) recorded in layer 4 of auditory cortex (ACx) before and after a test dose of nicotine (0.7mg/kg, s.c.) or saline. In "good" performers, nicotine enhanced LFP amplitude and decreased response threshold to characteristic frequency (CF) stimuli, yet had opposite effects (decreased amplitude, increased threshold) on responses to spectrally distant stimuli; i.e., cortical receptive fields became more selective for CF stimuli. In contrast, nicotine had little effect on LFP amplitude in "intermediate" or "poor" performing animals. Nicotine did, however, reduce LFP onset latency in all three groups, indicating that all received an effective dose of the drug. Our findings suggest that nicotinic regulation of cortical receptive fields may be a distinguishing feature of the best-performing animals, and may facilitate sensory-related learning by enhancing receptive field selectivity.

Nicotinic acetylcholine receptors in rat forebrain that bind 18F‐nifene: Relating PET imaging, autoradiography, and behavior

“…Given the auditory nature of the task, TSW binding may indicate that activation of nAChRs in the auditory thalamocortical pathway could increase thalamocortical relay of acoustic information and produce stronger cortical responses, which could underlie better performance. Such a mechanism is consistent with our prior finding that animals with better performance (using the same task as in the present study) exhibit stronger nicotinic enhancement of tone-evoked cortical responses(Liang et al, 2008). It is important to note, however, that the TSW includes not only thalamocortical axons but also corticothalamic projections.…”

“…Prior to training with tones, animals were shaped to escape shock (e.g., Liang et al, 2008). The goal of shaping was to promote running to the opposite side of the shuttlebox to minimize receipt of shock, which was escaped upon crossing the midline.…”

“…For example, nicotine-induced enhancement of auditory cortex function correlates well with auditory-cued behavior in rats, i.e., good performers on an active avoidance task exhibit stronger nicotine effects (Liang et al, 2008). Similarly, good performance on a cortex-dependent task is associated with a higher density of nAChRs in hippocampus and neocortex in rabbits (Li et al, 2008).…”

Nicotinic actions on neuronal networks for cognition: General principles and long-term consequences

“…Transdermal administration of nicotine to non-smokers does not affect cochlear activity but does affect the neural transmission of acoustic information [65]. A similar result was observed in the rat auditory cortex [66]. Critically, in this study antagonists of nAChRs reduced the evoked signal in the cortex, suggesting that endogenous ACh A c c e p t e d M a n u s c r i p t 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 11 acts through nAChRs to regulate thalamic transmission.…”

An acute dose, randomized trial of the effects of CDP-Choline on Mismatch Negativity (MMN) in healthy volunteers stratified by deviance detection level

“…Nicotinic receptor stimulation modulates the release of multiple neurotransmitters, and enhances tone-evoked physiological responsivity in the auditory cortex via activation of NMDA receptor-mediated glutamatergic neurotransmission (Flores-Hernandez et al 2009;Konradsson-Geuken et al 2009;Levy and Aoki 2002;Liang et al 2008;Metherate and Hsieh 2003;Metherate 2004;Yang et al 2013). nAChRs are abundantly expressed in the prefrontal cortex (PFC) and play a key role in the regulation of complex cognitive processes (Wallace and Bertrand 2013b).…”