PHYSIOLOGICAL CHARACTERIZATION OF VIP NEURONS FROM THE DORSAL RAPHE NUCLEUS AND THEIR ROLE IN NON-MOTOR SYMPTOMS OF PARKINSON’S DISEASE

The dorsal raphe nucleus (DRN) is a heterogeneous brain structure composed mainly of serotonergic and dopaminergic neurons, including a subpopulation expressing the vasoactive intestinal peptide (VIP). Recently, our team demonstrated that these VIP neurons are activated by salient threats, highlighting their involvement in vigilance behaviors. Vigilance is an adaptive state that enabling rapid detection and evaluation of environmental threats. However, the physiological properties of these neurons within the DRN remain poorly characterized. Moreover, vigilance is linked to anxiety, and its dysregulation can lead to pathological hypervigilance. Parkinson’s disease (PD), although defined by late-onset motor symptoms, also presents early non-motor features such as anxiety and attentional deficits that impair quality of life, yet the contribution of VIP neurons to PD remains unknown. This project aims to (1) map visual threat-related information to DRN VIP neurons; (2) assess threat-induced synaptic adaptations using patch-clamp and (3) examine anxiety and vigilance behaviors in a progressive mouse model of Parkinson’s with a focus on VIP neurons. Our results show that visual threat signals reach DRN VIP neurons through a restricted neural circuit involving the superior colliculus. We further demonstrate synaptic adaptations in these neurons 24 hours after threat exposure. Using a genetic model of Parkinson’s disease, we show α-synuclein accumulation at 18 months in the DRN, particularly in VIP neurons. These findings identify DRN VIP neurons as a critical hub for visual threat signals and reveal their selective vulnerability in Parkinson’s disease, shedding light on anxiety- and vigilance-related dysfunctions.