Guardian of excitability: Multifaceted role of galanin in whole brain excitability

Galanin is a neuropeptide, which is critically involved in homeostatic
processes like controlling arousal, sleep, and regulation of stress. This
extensive range of functions aligns with implications of galanin in
diverse pathologies, including anxiety disorders, depression, and
epilepsy. Here we investigated the regulatory function of galanin on
whole-brain activity in larval zebrafish using wide-field Ca2+ imaging.
Combining this with genetic perturbations of galanin signaling and
pharmacologically increasing neuronal activity, we are able to probe
actions of galanin across the entire brain. Our findings demonstrate that
under unperturbed conditions and during epileptic seizures, galanin exerts
a sedative influence on the brain, primarily through the galanin receptor
1a (galr1a). However, exposure to acute stressors like pentylenetetrazole
(PTZ) compromises galanin’s sedative effects, leading to overactivation of
the brain and increased seizure occurrence. Interestingly, galanin’s
impact on seizures appears to be bidirectional, as it can both decrease
seizure severity and increase seizure occurrence, potentially through
different galanin receptor subtypes. This nuanced interplay between
galanin and various physiological processes underscores its significance
in modulating stress-related pathways and suggests its potential
implications for neurological disorders such as epilepsy. Taken together,
our data sheds light on a multifaceted role of galanin, where galanin
regulates whole-brain activity but also shapes acute responses to stress.