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Spatial processing in the primary auditory cortex following cholinergic lesions of the basal forebrain in ferrets.

Nodal FR, Leach ND, Keating P, Dahmen JC, King AJ, Bajo VM (2013) Spatial processing in the primary auditory cortex following cholinergic lesions of the basal forebrain in ferrets. Neuroscience 2013 Abstracts 353.09. Society for Neuroscience, San Diego, CA.

Summary: Cortical acetylcholine release has been implicated in different cognitive functions, including perceptual learning. We have recently shown that cortical cholinergic innervation is necessary for normal sound localization accuracy in ferrets, as well as for their ability to adapt with training to altered spatial cues (Leach et al., 2013, J Neurosci 33:6659-71). To explore whether these behavioral deficits are associated with changes in the spatial sensitivity of cortical neurons, we recorded neural activity in the primary auditory cortex (A1) from three animals in which cholinergic inputs had previously been reduced by making bilateral injections of the immunotoxin ME20.4-SAP in the nucleus basalis (NB). Neural activity was recorded from 146 penetrations in the left and right A1 under anesthesia (medetomidine/ketamine) using Neuronexus multi-site silicon probes. Histological analysis after the recording sessions revealed a mean loss of cholinergic neurons in the NB of 89.3±7.1% when compared to control animals, as well as a significant reduction in cholinergic fiber density across the auditory cortex, including the middle ectosylvian gyrus where A1 is located. On the basis of the location of the penetrations and electrophysiological characterization of the neural responses, which typically exhibited a mean latency of ≤20 ms, frequency tuning and onset responses with occasional weaker offset responses, we were able to assign the recordings to A1. The distribution of unit best frequencies was used to ensure that the tonotopic axis of A1 was evenly sampled. Spatial tuning was determined using virtual acoustic space stimuli comprising 200 ms broadband noise presented at three different levels (56, 70 and 84 dB SPL) from 12 locations separated by 30° in azimuth. Most of the units were broadly tuned, responding to all the virtual sound locations tested. Their spatial preferences were quantified by calculating the centroid direction vector from the variation in spike count with stimulus location within the onset response. This revealed a contralateral preference for most units, with the majority of the centroid azimuths located within the frontal hemifield. These data are consistent with the distribution of azimuth tuning previously described in the ferret, and initial comparisons with control animals have not shown any differences in spatial sensitivity in the animals with cholinergic lesions. Reduced cholinergic release therefore does not appear to influence the spatial response properties of A1 neurons in anesthetized animals, suggesting that any effects on sensory coding may only become apparent during behavior.

Related Products: ME20.4-SAP (Cat. #IT-15)

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