ePoster

Control and coding of pupil size by hypothalamic orexin neurons

Nikola Grujic, Alexander Tesmer, Eva Bracey, Daria Peleg-Raibstein, Denis Burdakov
FENS Forum 2024(2024)
Messe Wien Exhibition & Congress Center, Vienna, Austria

Conference

FENS Forum 2024

Messe Wien Exhibition & Congress Center, Vienna, Austria

Resources

Authors & Affiliations

Nikola Grujic, Alexander Tesmer, Eva Bracey, Daria Peleg-Raibstein, Denis Burdakov

Abstract

Orexin neurons originate in the lateral hypothalamus, receive many inputs, and project throughout the brain. This puts them in an ideal position to integrate large amounts of information and signal them toward desired targets. We hypothesized that arousal, which impacts a variety of internal states and behaviours, could be one of these signals that orexin neurons transmit. To test this, we investigated the causal and correlative links between orexin neurons and pupil size, which is often taken as a readout of arousal. Optogenetic stimulation, 2-photon imaging, photometry, ablation, and pharmacological manipulation of orexin neurons were employed to establish these links. In addition, we investigated a possible downstream mechanism by which orexin could modulate pupil size, the strong projection to locus coeruleus (LC). Photo-stimulation of orexin neurons lead to stimulation-frequency-dependent pupillary dilation that was mediated by orexin peptide signaling, as confirmed by pharmacological blockade of orexin receptors. Ablating orexin neurons lead to a disruption in the well-described relationship between movement and pupil size. In terms of single unit coding schemes, we found that orexin neuron activity correlated very strongly with pupil size, and that orexin neurons multiplexed information about pupil size, reward, and movement. Finally, by selectively stimulating orexin projections to the LC, and by blocking LC noradrenergic signalling while simultaneously stimulating orexin neurons, we showed that LC is at least partially responsible for dilation. With these results we clearly establish the role of orexin in control of moment-to-moment arousal, significant for modulating neural processing and behaviour on many levels.

Unique ID: fens-24/control-coding-pupil-size-hypothalamic-3f98583e