| 1. |
- Serra, Gian Pietro, et al.
(författare)
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A role for the subthalamic nucleus in aversive learning
- 2023
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Ingår i: Cell Reports. - : Elsevier. - 2211-1247. ; 42:11
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 2. |
- Serra, Gian Pietro, et al.
(författare)
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Aversion encoded in the subthalamic nucleus
- 2024
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Activation of the subthalamic nucleus (STN) is associated with the stopping of ongoing behavior via the basal ganglia. However, we recently observed that optogenetic STN excitation induced a strong jumping/escaping behavior. We hypothesized that STN activation is aversive. To test this, place preference was assessed. Optogenetic excitation of the STN caused potent place aversion. Causality between STN activation and aversion has not been demonstrated previously. The lateral habenula (LHb) is a critical hub for aversion. Optogenetic stimulation of the STN indeed caused firing of LHb neurons, but with delay, suggesting the involvement of a polysynaptic circuit. To unravel a putative pathway, the ventral pallidum (VP) was investigated. VP receives projections from the STN and in turn projects to the LHb. Optogenetic excitation of STN-VP terminals caused firing of VP neurons and induced aversive behavior. This study identifies the STN as critical hub for aversion, potentially mediated via an STN-VP-LHb pathway.
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