Role of cerebellum in nociception processing

ANDRES P VARANI; SALA ROMAIN; VICTOR SABALSKI; CAROLINE MAILHES-HAMON ; CLEMENT LENA; DANIELA POPA

Congreso; XXXVI Annual Meeting (SAN2021); 2021

Classically described as a motor structure, the cerebellum is also implicated in a range of sensory behaviors such as nociception, emotion, learning, etc. Based on its anatomical and functional connectivity, we investigated the role of the cerebellar outputs in nociception modulation. We combined the use of a chemogenetic technique (DREADDs) expressed via viral vectors, finely tuning the activity of targeted structures, with acute nociceptive tests designed to assess the potential nociceptive modulation. Our results suggest that cerebellar outputs are implicated in nociceptive modulation and that this effect is carried out through specific glutamatergic cerebellar outputs pathways. In order to target glutamatergic cerebellar-thalamic pathways we combined the use of a CRE-recombinase expressing canine adenovirus-2 (CAV-2) with AAV-hSyn-DIO-hM4D(Gi)-mCherry (Inhibition) or AAV-hSyn-DIO-hM3D(Gq)-mCherry (Activation). We observed that thermal nociceptive responses evoked by the tail immersion, acetone and thermal place preference tests seems to be modulated by dentate(DN)-posteriomedial thalamus(Pom) and DN-centrolateral thalamus(CL) and DN-vetromedial thalamus(VM) projections. However, mechanical (Von Frey test) and chemical (capsaicin) nociceptive responses are controlled by DN-CL and DN-VM projections. In summary, our results suggest that distinct cerebellar-thalamic pathways are capable to modulate different modalities of acute nociception in rodents.