Oxytocin modulates neural processing of mitral/tufted cells in the olfactory bulb

Abstract

Aim Oxytocin plays an important role in social recognition in rodents, which is mediated predominantly by the olfactory system. Although oxytocin modulates neural activity in the olfactory bulb, the underlying mechanism is largely unknown. Here, we studied how direct infusion of oxytocin into the olfactory bulb affect social interactions in mice and modulate the neural activity of mitral/tufted cells in the olfactory bulb. Methods A three‐chamber social interaction test was used in the behavioural test. For in vivo studies, single unit recordings, local field potential recordings and fibre photometry recordings were used to record the neural activity of olfactory bulb. For in vitro studies, we performed patch clamp recordings in the slice of the olfactory bulb. Results Behaviourally, direct oxytocin infusion in olfactory bulb increased performance in a social interaction task. Moreover, odour‐evoked responses of mitral/tufted cells and neural discrimination of odours were both enhanced by oxytocin, whereas the spontaneous firing rate of mitral/tufted cells was reduced. At the neural network level, oxytocin decreased the amplitude of odour‐evoked high gamma responses. At the cell population level, oxytocin decreased odour‐evoked calcium responses (reflecting neural activity) specifically in granule cells. Moreover, in vitro slice recordings revealed that the inhibitory effect of oxytocin on mitral cell activity is mediated mainly by modulation of ATP‐sensitive potassium channels and involves the oxytocin receptor–Gq–PLC–IP3 signalling pathway. Conclusion Oxytocin modulates social interaction, likely by increasing the signal‐to‐noise ratio of odour responses in mitral cells which is partly through ATP‐sensitive potassium channel.

α-Synuclein aggregation in the olfactory bulb induces olfactory deficits by perturbing granule cells and granular–mitral synaptic transmission

“…All odors were presented for 2 s in a pseudorandom order, followed by an inter-stimulus interval of 20 s. For all the eight odors, except benzaldehyde, which is an aversive odor, the other seven odors are all neutral odors. We selected these odors since they usually evoke the strong responses in the electrophysiological recordings and they have been commonly used in our previous studies 27 , 60 – 62 .…”

Neural Functions of Hypothalamic Oxytocin and its Regulation

“…Interestingly, intrabulbar OT infusion can increase mouse performance in a social interaction task, enhance odor-evoked responses of mitral/tufted cells and neural discrimination of odors but reduce the spontaneous firing rate of mitral/tufted cells. OT also decreases odor-evoked calcium responses specifically in granule cells and modulates ATP-sensitive potassium channels to exert inhibitory effect on mitral cell activity through OTR-Gq-PLC-IP3 signalling pathway ( Sun et al, 2021 ). By contrast, excitatory outputs of olfactory nerves from mitral cells can mediate effects of IAO on the brain activity including OT neurons in the SON in rats ( Liu et al, 2017 ; Meddle et al, 2000 ; Yeomans et al, 2021 ).…”

“…Improve olfactory deficits in schizophrenia. (Osako et al, 2001;Sun et al, 2021;Woolley et al, 2015;Yu et al, 1996b) Hearing OT may promote the comparison-decision stage and modulate the activity of auditory system at multiple levels.…”

Translation: Bench to bedside—And back

“…This important work holds the potential of further investigating the potential benefit of therapeutic tetrahydrobiopterin supplementation. 13 Recent examples from cardiovascular medicine include pyruvate kinase muscle isozyme modulation to treat pulmonary hypertension, 14 the benefit of cholinergic stimulation, 15 and strategies to prevent and counteract cognitive impairment 16 or lysosomal pathologies 17 in cardiovascular disease.…”

“…A recent study by Sun et al 12 investigates the role of tetrahydrobiopterin in the etiology and pathogenesis of Duchenne's muscular dystrophy, the most common hereditary muscular disorder with reduced life expectancy and severely reduced quality of life, starting from the age of 2–3. This important work holds the potential of further investigating the potential benefit of therapeutic tetrahydrobiopterin supplementation 13 …”