Leptin modulates olfactory discrimination and neural activity in the olfactory bulb

Abstract

Aim Leptin is an important peptide hormone that regulates food intake and plays a crucial role in modulating olfactory function. Although a few previous studies have investigated the effect of leptin on odor perception and discrimination in rodents, research on the neural basis underlying the behavioral changes is lacking. Here we study how leptin affects behavioral performance during a go/no‐go task and how it modulates neural activity of mitral/tufted cells in the olfactory bulb, which plays an important role in odor information processing and representation. Methods A go/no‐go odor discrimination task was used in the behavioral test. For in vivo studies, single unit recordings, local field potential recordings and fiber photometry recordings were used. For in vitro studies, we performed patch clamp recordings in the slice of the olfactory bulb. Results Behaviorally, leptin affects performance and reaction time in a difficult odor‐discrimination task. Leptin decreases the spontaneous firing of single mitral/tufted cells, decreases the odor‐evoked beta and high gamma local field potential response, and has bidirectional effects on the odor‐evoked responses of single mitral/tufted cells. Leptin also inhibits the population calcium activity in genetically identified mitral/tufted cells and granule cells. Furthermore, in vitro slice recordings reveal that leptin inhibits mitral cell activity through direct modulation of the voltage‐sensitive potassium channel. Conclusions The behavioral reduction in odor discrimination observed after leptin administration is likely due to decreased neural activity in mitral/tufted cells, caused by modulation of potassium channels in these cells.

Excitability of Neural Activity is Enhanced, but Neural Discrimination of Odors is Slightly Decreased, in the Olfactory Bulb of Fasted Mice

“…The microelectrodes (16-channel, Jiangsu Brain Medical Technology Co. Ltd, Nanjing, China) were implanted into a specific region of the brain as previously described [18,19]. Briefly, mice were anesthetized with pentobarbital sodium (90 mg/kg body weight, i.p.)…”

Body-Mass-Index Associated Differences in Ortho- and Retronasal Olfactory Function and the Individual Significance of Olfaction in Health and Disease

“…Additionally, leptin-resistance (an adipose tissue hormone which regulates energy balance) may predispose or promote obesity [3]. Moreover, the leptin hormone may negatively affect olfaction in humans [4] and has been shown to reduce odor discrimination abilities in rodents [5].…”

A hunger for odour: Leptin modulation of olfaction

“…What additional insight was obtained in the new study by Sun et al? Mitral/tufted cells, which receive direct olfactory sensory neurone input are also directly modulated by a peptide secreted by adipocytes in the body signalling nutritional state and energy balance.…”

“…A report in this issue of Acta Physiologica describes how leptin, a hormone released by fat cells in the body, modulates olfactory system neural activity and odour perception in a manner that could promote homoeostatic regulation of responses to food odour. The mammalian olfactory system serves dual chemosensory functions.…”

“…Sun et al dissect this relationship between leptin and olfactory processing with a multi‐level technical approach, with a goal of understanding the mechanisms of leptin's direct effects on olfaction. Beginning with behavioural assessments, the authors demonstrate that leptin, either delivered systemically or directly into the olfactory bulbs, impairs odour discrimination in mice.…”