Dataset Information

Cortical ChAT+ neurons co-transmit acetylcholine and GABA in a target- and brain-region-specific manner.

ABSTRACT: The mouse cerebral cortex contains neurons that express choline acetyltransferase (ChAT) and are a potential local source of acetylcholine. However, the neurotransmitters released by cortical ChAT+ neurons and their synaptic connectivity are unknown. We show that the nearly all cortical ChAT+ neurons in mice are specialized VIP+ interneurons that release GABA strongly onto other inhibitory interneurons and acetylcholine sparsely onto layer 1 interneurons and other VIP+/ChAT+ interneurons. This differential transmission of ACh and GABA based on the postsynaptic target neuron is reflected in VIP+/ChAT+ interneuron pre-synaptic terminals, as quantitative molecular analysis shows that only a subset of these are specialized to release acetylcholine. In addition, we identify a separate, sparse population of non-VIP ChAT+ neurons in the medial prefrontal cortex with a distinct developmental origin that robustly release acetylcholine in layer 1. These results demonstrate both cortex-region heterogeneity in cortical ChAT+ interneurons and target-specific co-release of acetylcholine and GABA.

SUBMITTER: Granger AJ

PROVIDER: S-EPMC7360370 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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Publications

Cortical ChAT+ neurons co-transmit acetylcholine and GABA in a target- and brain-region-specific manner.

Granger Adam J AJ Wang Wengang W Robertson Keiramarie K El-Rifai Mahmoud M Zanello Andrea F AF Bistrong Karina K Saunders Arpiar A Chow Brian W BW Nuñez Vicente V Turrero García Miguel M Harwell Corey C CC Gu Chenghua C Sabatini Bernardo L BL

eLife 20200702

The mouse cerebral cortex contains neurons that express choline acetyltransferase (ChAT) and are a potential local source of acetylcholine. However, the neurotransmitters released by cortical ChAT+ neurons and their synaptic connectivity are unknown. We show that the nearly all cortical ChAT+ neurons in mice are specialized VIP+ interneurons that release GABA strongly onto other inhibitory interneurons and acetylcholine sparsely onto layer 1 interneurons and othe ...[more]

PMID: 32613945

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Project description:A unique population of ventral tegmental area (VTA) neurons co-transmits glutamate and GABA as well as functionally signals rewarding and aversive outcomes. However, the circuit inputs to VTA VGluT2+VGaT+ neurons are unknown, limiting our understanding of the functional capabilities of these neurons. To identify the inputs to VTA VGluT2+VGaT+ neurons, we coupled monosynaptic rabies tracing with intersectional genetic targeting of VTA VGluT2+VGaT+ neurons in mice. We found that VTA VGluT2+VGaT+ neurons received diverse brain-wide inputs. The largest numbers of monosynaptic inputs to VTA VGluT2+VGaT+ neurons were from superior colliculus, lateral hypothalamus, midbrain reticular nucleus, and periaqueductal gray, whereas the densest inputs relative to brain region volume were from dorsal raphe nucleus, lateral habenula, and ventral tegmental area. Based on these and prior data, we hypothesized that lateral hypothalamus and superior colliculus inputs were glutamatergic neurons. Optical activation of glutamatergic lateral hypothalamus neurons robustly activated VTA VGluT2+VGaT+ neurons regardless of stimulation frequency and resulted in flee-like ambulatory behavior. In contrast, optical activation of glutamatergic superior colliculus neurons activated VTA VGluT2+VGaT+ neurons for a brief period of time at high stimulation frequency and resulted in head rotation and arrested ambulatory behavior (freezing). For both pathways, behaviors induced by stimulation were uncorrelated with VTA VGluT2+VGaT+ neuron activity. However, stimulation of glutamatergic lateral hypothalamus neurons, but not glutamatergic superior colliculus neurons, was associated with VTA VGluT2+VGaT+ footshock-induced activity. We interpret these results such that inputs to VTA VGluT2+VGaT+ neurons may integrate diverse signals related to the detection and processing of motivationally-salient outcomes. Further, VTA VGluT2+VGaT+ neurons may signal threat-related outcomes, possibly via input from lateral hypothalamus glutamate neurons, but not threat-induced behavioral kinematics.

Dataset Information

Cortical ChAT+ neurons co-transmit acetylcholine and GABA in a target- and brain-region-specific manner.

Publications

Cortical ChAT<sup>+</sup> neurons co-transmit acetylcholine and GABA in a target- and brain-region-specific manner.

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