Periaqueductal efferents to dopamine and GABA neurons of the VTA.

Niels R Ntamati,Ridouane Achargui,Meaghan Creed,Christian Lüscher,Allan Siegel

doi:10.1371/journal.pone.0190297

Niels R Ntamati, Ridouane Achargui + Show 3 more

Open Access

https://doi.org/10.1371/journal.pone.0190297

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Journal: PloS one	Publication Date: Jan 5, 2018
Citations: 33	License type: CC BY 4.0

Affiliation: University of Geneva, University Hospital of Geneva

Abstract

Neurons in the periaqueductal gray (PAG) modulate threat responses and nociception. Activity in the ventral tegmental area (VTA) on the other hand can cause reinforcement and aversion. While in many situations these behaviors are related, the anatomical substrate of a crosstalk between the PAG and VTA remains poorly understood. Here we describe the anatomical and electrophysiological organization of the VTA-projecting PAG neurons. Using rabies-based, cell type-specific retrograde tracing, we observed that PAG to VTA projection neurons are evenly distributed along the rostro-caudal axis of the PAG, but concentrated in its posterior and ventrolateral segments. Optogenetic projection targeting demonstrated that the PAG-to-VTA pathway is predominantly excitatory and targets similar proportions of Ih-expressing VTA DA and GABA neurons. Taken together, these results set the framework for functional analysis of the interplay between PAG and VTA in the regulation of reward and aversion.

Highlights

The periaqueductal gray (PAG) is a heterogeneous midbrain structure that is critical for the endogenous modulation of nociception and for the expression of defensive behaviors [1]
ventral tegmental area (VTA) neurons co-expressing RVΔG-EGFP and the DIO-TVA-mCherry/RG constructs were identified as starter cells, from which the inputs were monosynaptically tagged by the expression of RVΔG-EGFP alone (Fig 1C)
We excluded the possibility of a direct, TVA-independent RVΔG-EGFP infection because no PAG efferents to VTA DA and gamma-aminobutyric acid (GABA) neurons neurons across the rostral, central and caudal PAG segments

Summary

Introduction

The periaqueductal gray (PAG) is a heterogeneous midbrain structure that is critical for the endogenous modulation of nociception and for the expression of defensive behaviors [1]. These functions have been shown to be mediated by neurons anatomically segregated in the longitudinal columns corresponding to the dorsolateral (dl), lateral (l) and ventrolateral (vl) subdivisions of the PAG [2]. Anatomical tracing studies have described ascending and descending projections from the PAG to a variety of brain structures [5]. Among these projection targets is the ventral tegmental area (VTA), a major component of the brain reward system [6]. The engagement of VTA dopamine- (DA) and gamma-aminobutyric acid (GABA)-releasing neurons with PAG afferents through both symmetric and asymmetric synaptic contacts has been demonstrated with rabies-assisted retrograde tracing and ultrastructural immunoelectron microscopic analyses [13,14]

Results

Discussion

Conclusion