Vestibular CCK signaling drives motion sickness-like behavior in mice

Area of Science:

• Neuroscience
• Physiology
• Behavioral Science

Background:

• Motion sickness (MS) is a common condition triggered by sensory conflicts during travel.
• The vestibular nuclei (VN) process motion information and are implicated in MS.
• The specific neural pathways and cell types responsible for MS symptoms are not fully understood.

Purpose of the Study:

• To identify the specific neurons within the VN that mediate the autonomic and aversive responses associated with motion sickness.
• To elucidate the downstream neural pathways activated by VN neurons during motion-induced malaise.
• To explore potential therapeutic targets for mitigating motion sickness.

Main Methods:

• Utilized genetic and neuroanatomical techniques to identify and characterize specific neuronal populations in the VN.
• Investigated the role of cholecystokinin (CCK)-expressing VN neurons in response to motion stimuli.
• Examined the downstream effects of CCK VN projections on other brain regions, including the parabrachial nucleus and its Calca-expressing neurons.
• Assessed the impact of CCK-A receptor antagonism on motion-induced aversive behaviors.

Main Results:

• Identified cholecystokinin (CCK)-expressing neurons in the vestibular nuclei (VN) as critical mediators of motion-induced malaise.
• Demonstrated that CCK VN projections to the parabrachial nucleus activate Calca-expressing neurons.
• Showed that CCK VN signaling is sufficient to induce avoidance learning, a key component of malaise, which can be blocked by CCK-A receptor antagonists.

Conclusions:

• CCK-expressing VN neurons play a central role in the neurobiological underpinnings of motion sickness.
• The CCK VN-parabrachial nucleus pathway, involving Calca-expressing neurons, is a key circuit for generating MS-related aversions.
• Targeting CCK signaling presents a promising therapeutic strategy for treating motion sickness.