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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.

2026-07-27 neuroscience
10.64898/2026.07.22.740090 bioRxiv
Show 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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