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C5 Alteration of threat processing in the bachd rat model of huntington’s disease relies on dysfunction of central amygdala
  1. Libo Yu-Taeger1,2,
  2. Charlotte Lamirault3,
  3. Valérie Doyère3,
  4. Olaf Riess1,2,
  5. Nicole El Massioui3,
  6. Huu Phuc Nguyen1,2
  1. 1Department of Medical Genetics, University of Tuebingen, Tuebingen, Germany
  2. 2Centre for Rare Diseases, University of Tuebingen, Tuebingen, Germany
  3. 3Institut des Neurosciences Paris-Saclay (Neuro-PSI), UMR 9197, Université Paris Sud, CNRS, Université Paris Saclay, Orsay, France

Abstract

Background In Huntington’s disease (HD), dysfunctional affective processes emerge as key symptoms of disturbances. In human HD and transgenic rat models of the disease, the amygdala was previously shown to have a reduced volume and carry a high load of mutant huntingtin (mHTT) aggregates. In search of the pathophysiology of affective dysregulation in HD, we hypothesised a specific role of the central amygdala (CeA), known to be particularly involved in emotional regulation.

Methods Using transgenic BACHD rats carrying full-length human mHTT, we first compared behavioural consequences of pharmacological modulation of CeA function by infusing GABAA receptor (GABAAR) antagonist picrotoxinin into ~4.5 month old BACHD and WT rats before confronting them to a threatening stimulus in two tasks: social interaction and signalled active avoidance.

Results Our results show that modulating the CeA induced differential behaviour between WT and BACHD rats. Second, we analysed amygdala alteration/dysfunction at the cellular level. An age-dependent increase in number and size of mHTT aggregates was observed specifically in the CeA of BACHD rats (between 3 and 6 months). No alteration of GABA and GABAAR expression levels, but an increased neuronal reactivity (Arc labelling) to a threatening stimulus in the medial part of this nucleus in 4.5 months old BACHD rats was found.

Conclusions These results suggest a basal pathological hyper-activity in the CeA (in particular its medial part) in the transgenic animals. Such amygdala dysfunction could account, at least in part, for affective symptoms in HD patients.

  • BACHD rats
  • Amygdala
  • threat processing

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