Regulation of cholinergic basal forebrain development, connectivity, and function by neurotrophin receptors.

Zoran Boskovic,Sonja Meier,Yunpeng Wang,Elizabeth J Coulson,Angelo Tedoldi,Michael R Milne,Tessa Onraet

doi:10.1042/ns20180066

Zoran Boskovic, Sonja Meier + Show 5 more

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https://doi.org/10.1042/ns20180066

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Abstract

Cholinergic basal forebrain (cBF) neurons are defined by their expression of the p75 neurotrophin receptor (p75NTR) and tropomyosin-related kinase (Trk) neurotrophin receptors in addition to cholinergic markers. It is known that the neurotrophins, particularly nerve growth factor (NGF), mediate cholinergic neuronal development and maintenance. However, the role of neurotrophin signalling in regulating adult cBF function is less clear, although in dementia, trophic signalling is reduced and p75NTR mediates neurodegeneration of cBF neurons. Here we review the current understanding of how cBF neurons are regulated by neurotrophins which activate p75NTR and TrkA, B or C to influence the critical role that these neurons play in normal cortical function, particularly higher order cognition. Specifically, we describe the current evidence that neurotrophins regulate the development of basal forebrain neurons and their role in maintaining and modifying mature basal forebrain synaptic and cortical microcircuit connectivity. Understanding the role neurotrophin signalling plays in regulating the precision of cholinergic connectivity will contribute to the understanding of normal cognitive processes and will likely provide additional ideas for designing improved therapies for the treatment of neurological disease in which cholinergic dysfunction has been demonstrated.

Highlights

Neurotrophin receptors in cholinergic basal forebrain neuronsOne of the defining features of the cholinergic basal forebrain neurons is their expression of the neurotrophin receptors, p75 neurotrophin receptor (p75NTR) and tropomyosin-related kinase A (TrkA), TrkB and TrkC, the receptors for nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and neurotrophins 3 and 4 (NT3/4).By binding to their cognate Trk and pan p75NTR receptors, neurotrophins mediate an array of morphological effects in mature neurons, which have been extensively reviewed elsewhere [1,2–4]
CBF neurons are regulated by neurotrophins through their receptors from as early as cell specification and differentiation, mediating the extent of their cholinergic phenotype, and controlling axonal outgrowth and target innervation
In addition it is clear that the adult expression of neurotrophin receptors in cholinergic basal forebrain (cBF) neurons regulates aspects of cell morphology, both growth and degeneration, which in turn can affect cortical function and behaviour

Summary

Introduction

Neurotrophin receptors in cholinergic basal forebrain neuronsOne of the defining features of the cholinergic basal forebrain (cBF) neurons is their expression of the neurotrophin receptors, p75 neurotrophin receptor (p75NTR) and tropomyosin-related kinase A (TrkA), TrkB and TrkC, the receptors for nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and neurotrophins 3 and 4 (NT3/4).By binding to their cognate Trk and pan p75NTR receptors, neurotrophins mediate an array of morphological effects in mature neurons, which have been extensively reviewed elsewhere [1,2–4].

Results

Conclusion