4.7 Article

Loss of mGluR5 in D1 Receptor-Expressing Neurons Improves Stress Coping

Journal

Publisher

MDPI
DOI: 10.3390/ijms22157826

Keywords

mGluR5; D1; stress; anxiety; memory; social behavior

Funding

  1. Austrian Science Fund (Fonds zur Forderung der Wissenschaftlichen Forschung) [W12060-B10, W12060-B12]
  2. GO-Bio grant from the German Science Ministry (Bundesministerium fur Bildung und Forschung)
  3. Austrian Science Fund (FWF)

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The study found that mGluR5(D1) cKO mice exhibited different coping mechanisms in response to escapable and inescapable stress, highlighting the functional integration of the dopaminergic and glutamatergic systems in controlling internal states upon stress exposure. The study directly implicates D1 neurons and mGluR5 as crucial mediators of behavioral stress responses.
The metabotropic glutamate receptor type 5 (mGluR5) has been proposed to play a crucial role in the selection and regulation of cognitive, affective, and emotional behaviors. However, the mechanisms by which these receptors mediate these effects remain largely unexplored. Here, we studied the role of mGluR5 located in D1 receptor-expressing (D1) neurons in the manifestation of different behavioral expressions. Mice with conditional knockout (cKO) of mGluR5 in D1 neurons (mGluR5(D1) cKO) and littermate controls displayed similar phenotypical profiles in relation to memory expression, anxiety, and social behaviors. However, mGluR5(D1) cKO mice presented different coping mechanisms in response to acute escapable or inescapable stress. mGluR5(D1) cKO mice adopted an enhanced active stress coping strategy upon exposure to escapable stress in the two-way active avoidance (TWA) task and a greater passive strategy upon exposure to inescapable stress in the forced swim test (FST). In summary, this work provides evidence for a functional integration of the dopaminergic and glutamatergic system to mediate control over internal states upon stress exposure and directly implicates D1 neurons and mGluR5 as crucial mediators of behavioral stress responses.

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