Cotransmission of acetylcholine and GABA

Abstract

Neurons that produce acetylcholine (ACh) are positioned to broadly influence the brain, with axonal arborizations that extend throughout the cerebral cortex, striatum, and hippocampus. While the action of these neurons has typically been attributed entirely to ACh, neurons often release more than one primary neurotransmitter. Here, we review evidence for the cotransmission of the inhibitory neurotransmitter GABA from cholinergic neurons throughout the mammalian central nervous system. Functional cotransmission of ACh and GABA has been reported in the retina and cortex, and anatomical studies suggest that GABA cotransmission is a common feature of nearly all forebrain ACh-producing neurons. Further experiments are necessary to confirm the extent of GABA cotransmission from cholinergic neurons, and the contribution of GABA needs to be considered when studying the functional impact of activity in ACh-producing neurons. This article is part of the Special Issue entitled 'Synaptopathy--from Biology to Therapy'.

Keywords: Acetylcholine; Cotransmission; GABA; Neurotransmitter corelease.

Figure 1

ChAT-expressing subcortical neurons also express Gad1/Gad2. A) Sagittal (+2.15 mm from midline) diagram of the mouse brain showing region of interest. Red and blue boxes indicate the areas of interest in (B) and (C), respectively. Str – Striatum, GP – Globus Pallidus, NB – Nucleus Basalis, D – dorsal, V- ventral, R – rostral, C – caudal. B) Low (left) and high (right) magnification example confocal image of the border between GP and NB, demonstrating fluorescent in situ hybridization for chat (magenta, top) and a combined probe for Gad1 and Gad2 (green, middle). Arrow heads indicate the position of ChAT-expressing neurons of the GP (top), with corresponding Gad1/Gad2 expression (middle). Merged images includes DAPI stain showing cell nuclei (blue, bottom). Insets show magnified view of individual neuron indicate by the asterisk (*). C) Same as in (B), but showing the NB proper. Scale is consistent with bars indicated in (B).