431. USING THE LIVE RAT STRESS PARADIGM TO INVESTIGATE APPROACH-AVOIDANCE BEHAVIOUR RELEVANT TO PSYCHIATRIC DISORDERS
Notice bibliographique
Résumé
Abstract Background Chronic stress is a well-known antecedent to the development of mental health disorders, such as depression. Corticotrophin releasing hormone (CRH) neurons in the paraventricular nucleus of the hypothalamus (PVNCRH) are known to play a key role in the neuroendocrine response to stress. However, we, and others, have recently shown that the PVNCRH neurons have non-neuroendocrine (synaptic) actions that directly and rapidly alter behaviour, resulting in lasting changes to stress coping and motivation. The contribution of the neural actions of the PVNCRH neurons to disorders such as depression, and how subpopulations of PVNCRH neurons may contribute to depression symptoms such as altered motivation, remains to be determined. Aims & Objectives Establish the live rat stress paradigm to assess changes in motivational conflict behaviours while undertaking neural recordings. Method To investigate the response of PVNCRH neurons, we used double transgenic CRH-cre x GCaMP6f mice to drive selective expression of the calcium indicator GCaMP6f in PVNCRH neurons. GRIN lens were implanted above the PVN, and miniature microscopes (Inscopix) were used to record the activity of individual PVNCRH neurons. To examine approach-avoidance behaviour under motivational conflict and associated neural activity, the live rat stress paradigm was utilised while undertaking both PVNCRH neural recording and video recording. Testing conditions were hungry (16 hours fasting) or sated mice and exposure to live rat or 3D-printed control. Testing was undertaken in a controlled setting whereby an arena was divided into mouse (40x40cm) and rat (20x40cm) areas, separated by a transparent, perforated wall. Mice could access sugar pellets adjacent to the perforated wall and the rat side of the area (approach behaviour) or retreat to a safe "hide" zone away from the perforated wall (avoidance behaviour). Results Creating a lens tract with a 29G needle prior to slow lens implantation limited tissue compression and facilitated deep hypothalamic imaging, with up to 25 neurons simultaneously recorded in individual animals. Results indicated the rat exposed fasted animals showed higher approach behaviour, with increased time spent in the feeding zone (subsequently near the live rat) compared to sated animals (41.4%±11.0 vs. 25.7%±14.4) and consumed significantly more pellets (35.0±9.0 vs. 8.0±4.0). Comparatively, fasted animals exposed to the live rat spent less time in the feeding zone than those exposed to the 3D-printed control (41.4%±10.97 vs. 86.9%±7.6) and spent more time avoiding in the hide zone than those exposed to the 3D-printed control (23.7%±11.7 vs. 2.5%±2.5). These results indicate different satiety states motivate approach behaviour towards the live rat as expected. Discussion & Conclusions This work established the use of the live rat stress paradigm as a means of investigating altered approach-avoidance behaviour in models of neuropsychiatric disorders such as depression. Ongoing analysis of neural activity is being used to evaluate how the activity of individual PVNCRH neurons is modulated during approach-avoidance behaviours by satiety state. Future studies will aim to use the recording and testing approaches trialled here in combination with a model of depression, to investigate potential role of the PVNCRH neurons in altered motivation and approach-avoidance behaviour.
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Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,001 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,001 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,001 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,001 |
| Intégrité de la recherche | 0,001 | 0,002 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,007 | 0,001 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule source (Gemma direct ou Codex distillé), pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».