PhD Scientific Days 2022

Neurosciences II.

The role of different neuron types in the median raphe region in depressive-like behaviour and concomitant changes in body temperature regulation

Text of the abstract

Introduction: The midbrain median raphe region (MRR) has been linked to numerous different behaviours and stress adaptation, but its effect on vegetative functions is debated. Additionally, it is unknown if there is connection between them. The MRR is mostly known for its serotonergic (SERT+) neurons, although they constitute a minor population of the nucleus. Interestingly, there is also a subpopulation of corticotrophin releasing hormone positive (CRH+) cells, which molecule is associated to stress.
Aims: Our aim was to investigate the role of MRR, especially its SERT+ and CRH+ neurons in depressive-like behaviour in parallel with changes in core body temperature (BT) as a vegetative function
Methods: Using pharmacogenetics control, excitatory and inhibitory designer receptors (DREADDs) were expressed in the mouse MRR. A biotelemetry system was implanted into the abdominal cavity to monitor changes in BT. Following injection of clozapine-N-oxide (CNO), the ligand for DREADDs, behavioural tests were performed. Depressive-like behaviour and cold stress reactivity was measured by the forced swim test (FST) at 23°C water temperature. The same protocol was repeated in SERT-Cre and CRH-Cre mice, expressing the DREADD only in the SERT+ or CRH+ cells of the MRR, respectively, but only with control and excitatory groups.
Results: The excitation of the MRR during FST increased floating, while marginally decreased struggling. The drop in BT was smaller after stimulating all neurones of the MRR, both during and after the test. In the SERT-Cre mice excitation of MRR SERT+ neurons marginally increased floating and significantly decreased struggling. Furthermore, the previously seen decrease in BT to FST after whole MRR stimulation was reproduced in the SERT-Cre excitatory group. The excitation of CRH+ cells did not affect the behaviour or the body temperature.
Conclusions: We showed that the MRR effectively regulates depressive-like behaviour as well as BT, in which SERT+, but not CRH+ neurons are involved. This finding may have clinical relevance in human depressive disorders.
Funding: Supported by the ÚNKP-21-3 New National Excellence Program of the Ministry for Innovation and Technology from the source of the National Research, Development and Innovation Fund; ERC-2011-ADG-294313; OTKA (grant numbers K120311, K131406); bilateral Balaton Program (TÉT_15-1-2016-003).