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Description
Lateral hypothalamic orexin/hypocretin (OH) circuits are required for stable consciousness and loss of OH signals cause narcolepsy in humans, dogs and mice. While it was previously shown that OH predominantly activates deep cortical layers responsible for cortical brain state dynamics, here we show that orexin knockout (KO) causes a striking 50% reduction in the amplitude of fast glutamatergic AMPA-receptor responses in layer 4 to 2/3 circuits of mouse primary visual cortex (V1), suggesting impaired synaptic plasticity. Indeed, orexin KO mice show impaired ocular dominance plasticity (ODP), an established in vivo model of experience-dependent visual plasticity, apparent in both juvenile(P28-35) and adult (>P110) mice. While intranasal application of orexin-A has previously alleviated age-related cognitive decline, we only observed a subtle enhancement of ODP in adult WT and KO-mice after intranasal orexin-A application.
On a behavioural/perceptual level, orexin KO mice were worse in orientation discrimination, needing a larger angle difference to discriminate square wave patterns, suggesting that processing of visual signals might also be affected. We therefore tested whether orexin KO would affect V1 novelty signals using an oddball paradigm and recorded visually evoked potentials (VEP) in anaesthetized mice: in V1 of orexin KO mice, typical VEP peaks were delayed compared to WT-controls. Similarly, differential context dependent activation of V1 by novel versus adapted stimuli was delayed in orexin KO mice.
Together our data show that OH circuits affect vision on multiple levels, including local circuit transmission, visual processing, plasticity and perception.
