TY - JOUR
T1 - Characterizing and TRAPing a Social Stress-Activated Neuronal Ensemble in the Ventral Tegmental Area
AU - Koutlas, Ioannis
AU - Linders, Louisa E
AU - van der Starre, Stef E
AU - Wolterink-Donselaar, Inge G
AU - Adan, Roger A H
AU - Meye, Frank J
N1 - Funding Information:
This work was supported by the NWO Gravitation project BRAINSCAPES: A Roadmap from Neurogenetics to Neurobiology (024.004.012), and by the ERC under the European Union’s Horizon 2020 research and innovation programme (grant agreement 804089; ReCoDE).
Publisher Copyright:
Copyright © 2022 Koutlas, Linders, van der Starre, Wolterink-Donselaar, Adan and Meye.
PY - 2022
Y1 - 2022
N2 - Social stress is a major contributor to neuropsychiatric issues such as depression, substance abuse and eating disorders. The ventral tegmental area (VTA) is involved in the effects of stress on cognitive and emotional processes perturbed in these disorders. However, the VTA is a cellularly heterogeneous brain area and it remains unclear which of its neuronal populations make up the social stress-sensitive ensemble. The current study characterizes the molecular, topographical and functional properties of VTA social stress-activated cells. First, we used immunohistochemical analysis of Fos protein, a marker of recent increased neuronal activity, to show that acute social stress activates a mainly neuronal ensemble in the VTA (VTA
Social stress neurons). Topographical analysis showed that this ensemble, which comprises ∼11% of all VTA neurons, occurs across VTA subregions. Further analysis showed that approximately half of the VTA
Social stress neurons express the dopamine synthesis rate-limiting enzyme tyrosine hydroxylase (TH). In a minority of cases this occurred with coexpression of vesicular glutamate transporter 2 (Vglut2). Also part of the ensemble were VTA cells expressing just Vglut2 without TH, and cells expressing the vesicular GABA transporter (VGAT) without TH. Next, using targeted recombination in active populations (TRAP2), we showed that VTA
Social stress neurons can be permanently tagged and made tractable for future functional investigations. Using a combination of TRAP2 and patch-clamp electrophysiology we demonstrate that VTA
Social stress neurons exhibit higher excitability than their non-TRAPed neighbor cells. Overall, this study shows that acute social stress activates an ensemble of neurons throughout the VTA, comprising distinct molecular identities, and with specific electrophysiological features. It also identifies TRAP2 as a tool to make this ensemble tractable for future functional studies.
AB - Social stress is a major contributor to neuropsychiatric issues such as depression, substance abuse and eating disorders. The ventral tegmental area (VTA) is involved in the effects of stress on cognitive and emotional processes perturbed in these disorders. However, the VTA is a cellularly heterogeneous brain area and it remains unclear which of its neuronal populations make up the social stress-sensitive ensemble. The current study characterizes the molecular, topographical and functional properties of VTA social stress-activated cells. First, we used immunohistochemical analysis of Fos protein, a marker of recent increased neuronal activity, to show that acute social stress activates a mainly neuronal ensemble in the VTA (VTA
Social stress neurons). Topographical analysis showed that this ensemble, which comprises ∼11% of all VTA neurons, occurs across VTA subregions. Further analysis showed that approximately half of the VTA
Social stress neurons express the dopamine synthesis rate-limiting enzyme tyrosine hydroxylase (TH). In a minority of cases this occurred with coexpression of vesicular glutamate transporter 2 (Vglut2). Also part of the ensemble were VTA cells expressing just Vglut2 without TH, and cells expressing the vesicular GABA transporter (VGAT) without TH. Next, using targeted recombination in active populations (TRAP2), we showed that VTA
Social stress neurons can be permanently tagged and made tractable for future functional investigations. Using a combination of TRAP2 and patch-clamp electrophysiology we demonstrate that VTA
Social stress neurons exhibit higher excitability than their non-TRAPed neighbor cells. Overall, this study shows that acute social stress activates an ensemble of neurons throughout the VTA, comprising distinct molecular identities, and with specific electrophysiological features. It also identifies TRAP2 as a tool to make this ensemble tractable for future functional studies.
KW - TRAP2
KW - c-Fos
KW - dopamine
KW - excitability characterizing a VTA social stress ensemble
KW - neuronal ensemble
KW - social stress
KW - ventral tegmental area
UR - http://www.scopus.com/inward/record.url?scp=85134711615&partnerID=8YFLogxK
U2 - 10.3389/fnbeh.2022.936087
DO - 10.3389/fnbeh.2022.936087
M3 - Article
C2 - 35874648
SN - 1662-5153
VL - 16
JO - Frontiers in Behavioral Neuroscience [E]
JF - Frontiers in Behavioral Neuroscience [E]
M1 - 936087
ER -