A role for the subthalamic nucleus in aversive learning
Cell Reports. 2023-11-01; 42(11): 113328
DOI: 10.1016/j.celrep.2023.113328
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Serra GP(1), Guillaumin A(2), Vlcek B(1), Delgado-Zabalza L(3), Ricci A(1), Rubino E(1), Dumas S(4), Baufreton J(3), Georges F(3), Wallén-Mackenzie Å(5).
Author information:
(1)Uppsala University, Department of Organism Biology, 752 36 Uppsala, Sweden.
(2)Uppsala University, Department of Organism Biology, 752 36 Uppsala, Sweden;
University of Bordeaux, CNRS, IMN, UMR 5293, 33000 Bordeaux, France.
(3)University of Bordeaux, CNRS, IMN, UMR 5293, 33000 Bordeaux, France.
(4)Oramacell, Paris, France.
(5)Uppsala University, Department of Organism Biology, 752 36 Uppsala, Sweden.
Electronic address: .
The subthalamic nucleus (STN) is critical for behavioral control; its
dysregulation consequently correlated with neurological and neuropsychiatric
disorders, including Parkinson’s disease. Deep brain stimulation (DBS) targeting
the STN successfully alleviates parkinsonian motor symptoms. However, low mood
and depression are affective side effects. STN is adjoined with para-STN,
associated with appetitive and aversive behavior. DBS aimed at STN might
unintentionally modulate para-STN, causing aversion. Alternatively, the STN
mediates aversion. To investigate causality between STN and aversion, affective
behavior is addressed using optogenetics in mice. Selective promoters allow
dissociation of STN (e.g., Pitx2) vs. para-STN (Tac1). Acute photostimulation
results in aversion via both STN and para-STN. However, only STN
stimulation-paired cues cause conditioned avoidance and only STN stimulation
interrupts on-going sugar self-administration. Electrophysiological recordings
identify post-synaptic responses in pallidal neurons, and selective
photostimulation of STN terminals in the ventral pallidum replicates STN-induced
aversion. Identifying STN as a source of aversive learning contributes
neurobiological underpinnings to emotional affect.
Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.
Conflict of interest statement: Declaration of interests S.D. is the owner of Oramacell, Paris, France.