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bioRxiv · 10.64898/2026.07.22.740090

Insulin controls olfactory gain at the first central synapse by regulating periglomerular neuron excitability

Oncul, M.·Stefens, C.·Smith, E. L.·Choudhuri, S.·Filippi, B. M.·Johnston, J.
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Abstract

Sensory processing is dynamically tuned by internal state, yet how metabolic signals reshape the earliest stages of sensory circuits remains poorly understood. Here we identify a circuit mechanism by which satiety suppresses olfactory sensitivity at the first central synapse in the mouse olfactory bulb. Using a within-animal paradigm modelling fasted and glucose-induced sated states, we show that satiety impairs food-finding behaviour and reduces olfactory receptor neuron input to the olfactory bulb. Periglomerular (PG) cells, which co-express insulin receptors and the potassium channel Kv1.3, mediate this effect: insulin inhibits the low-voltage-activated Kv1.3 current in PG cells, increasing their spontaneous and odour-evoked activity. This heightened PG cell activity drives enhanced presynaptic inhibition of olfactory receptor neuron terminals, dampening sensory input before it reaches mitral cells. These findings establish insulin-dependent presynaptic inhibition of PG cells as a key locus of state-dependent sensory gain control.

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Oncul, M., Stefens, C., Smith, E. L., Choudhuri, S., Filippi, B. M., Johnston, J.. 2026-07-27. Insulin controls olfactory gain at the first central synapse by regulating periglomerular neuron excitability. https://doi.org/10.64898/2026.07.22.740090

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