Abstract

Cholinergic inputs to the auditory cortex can modulate sensory processing and regulate stimulus-specific plasticity according to the behavioural state of the subject. In order to understand how acetylcholine achieves this, it is essential to elucidate the circuitry by which cholinergic inputs influence the cortex. In this study, we described the distribution of cholinergic neurons in the basal forebrain and their inputs to the auditory cortex of the ferret, a species used increasingly in studies of auditory learning and plasticity. Cholinergic neurons in the basal forebrain, visualized by choline acetyltransferase and p75 neurotrophin receptor immunocytochemistry, were distributed through the medial septum, diagonal band of Broca, and nucleus basalis magnocellularis. Epipial tracer deposits and injections of the immunotoxin ME20.4-SAP (monoclonal antibody specific for the p75 neurotrophin receptor conjugated to saporin) in the auditory cortex showed that cholinergic inputs originate almost exclusively in the ipsilateral nucleus basalis. Moreover, tracer injections in the nucleus basalis revealed a pattern of labelled fibres and terminal fields that resembled acetylcholinesterase fibre staining in the auditory cortex, with the heaviest labelling in layers II/III and in the infragranular layers. Labelled fibres with small en-passant varicosities and simple terminal swellings were observed throughout all auditory cortical regions. The widespread distribution of cholinergic inputs from the nucleus basalis to both primary and higher level areas of the auditory cortex suggests that acetylcholine is likely to be involved in modulating many aspects of auditory processing.

Highlights

  • The central cholinergic system has been characterized in a number of animal species, including rodents and primates (Mesulam et al, 1984; Saper, 1984; Woolf, 1991)

  • The description of the cholinergic cells in the basal forebrain (BF) and of the AChE fibres in the ferret auditory cortex was based on data from three animals, whereas two additional cases were used to describe the co-localization of choline acetyltransferease (ChAT)- and p75NTR-positive cells and putative GABAergic cells in the nucleus basalis magnocellularis (NB)

  • Cholinergic neurons in the ferret BF (Ch1–4) formed a continuum that extended from the medial septum (MS) (Ch1), which is the most anterior and medial region, via the diagonal band of Broca vertical limb (VDB) (Ch2) and diagonal band of Broca horizontal limb (HDB) (Ch3), to the most posterior and lateral structure, the NB (Ch4; Figs 2–4)

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Summary

Introduction

The central cholinergic system has been characterized in a number of animal species, including rodents and primates (Mesulam et al, 1984; Saper, 1984; Woolf, 1991). The basal forebrain (BF) cholinergic complex, encompassing the medial septum (MS), horizontal and vertical limbs of the diagonal band of Broca (HDB and VDB, respectively) and nucleus basalis magnocellularis (NB), provides the majority of the cholinergic innervation to the sensory, motor and prefrontal cortices and to the hippocampus (Semba & Fibiger, 1989). Of these BF regions, the NB provides the majority of the cholinergic input to the sensory cortices (Saper, 1984; Henderson, 1987a; Kamke et al, 2005a).

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