RESUMO
In mammals, odour information within the olfactory bulb (OB) is processed by complex neural circuits before being ultimately represented in the action potential activity of mitral/tufted cells (M/Ts). Cholecystokinin-expressing (CCK+) superficial tufted cells (sTCs) are a subset of tufted cells that potentially contribute to olfactory processing in the OB by orchestrating M/T activity. However, the exact role of CCK+ sTCs in modulating odour processing and olfactory function in vivo is largely unknown. Here, we demonstrate that manipulating CCK+ sTCs can generate perception and induce place avoidance. Optogenetic activation/inactivation of CCK+ sTCs exerted strong but differing effects on spontaneous and odour-evoked M/T firing. Furthermore, inactivation of CCK+ sTCs disrupted M/T odour encoding and impaired olfactory detection and odour discrimination. These results establish the role of CCK+ sTCs in odour representation and olfactory behaviours. KEY POINTS: Mice could perceive the activity of CCK+ sTCs and show place avoidance to CCK+ sTC inactivation. Optical activation of CCK+ sTCs increased the percentage of cells with odour response but reduced the odour-evoked response in M/Ts in awake mice. Optical inactivation of CCK+ sTCs greatly decreased spontaneous firing and odour-evoked response in M/Ts. Inactivation of CCK+ sTCs impairs the odour decoding performance of M/Ts and disrupts odour detection and discrimination behaviours in mice. These results indicate that CCK+ sTCs participate in modulating the odour representation and maintaining normal olfactory-related behaviours.
Assuntos
Colecistocinina , Bulbo Olfatório , Animais , Feminino , Masculino , Camundongos , Colecistocinina/metabolismo , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Neurônios/fisiologia , Odorantes , Bulbo Olfatório/fisiologia , Percepção Olfatória/fisiologia , Optogenética , Olfato/fisiologiaRESUMO
Mammalian olfactory epithelium has the capacity of self-renewal throughout life. Aging is one of the major causes leading to the olfactory dysfunction. Here, we performed single-cell RNA sequencing (scRNA-seq) analysis on young and aged murine olfactory epithelium (OE) and identified aging-related differentially expressed genes (DEGs) throughout 21 cell types. Aging led to the presence of activated horizontal basal cells (HBCs) in the OE and promoted cellular interaction between HBCs and neutrophils. Aging enhanced the expression of Egr1 and Fos in sustentacular cell differentiation from multipotent progenitors, whereas Bcl11b was downregulated during the sensory neuronal homeostasis in the aged OE. Egr1 and Cebpb were predictive core regulatory factors of the transcriptional network in the OE. Overexpression of Egr1 in aged OE organoids promoted cell proliferation and neuronal differentiation. Moreover, aging altered expression levels and frequencies of olfactory receptors. These findings provide a cellular and molecular framework of OE aging at the single-cell resolution.
RESUMO
Grooming, as an evolutionarily conserved repetitive behavior, is common in various animals, including humans, and serves essential functions including, but not limited to, hygiene maintenance, thermoregulation, de-arousal, stress reduction, and social behaviors. In rodents, grooming involves a patterned and sequenced structure, known as the syntactic chain with four phases that comprise repeated stereotyped movements happening in a cephalocaudal progression style, beginning from the nose to the face, to the head, and finally ending with body licking. The context-dependent occurrence of grooming behavior indicates its adaptive significance. This review briefly summarizes the neural substrates responsible for rodent grooming behavior and explores its relevance in rodent models of neuropsychiatric disorders and neurodegenerative diseases with aberrant grooming phenotypes. We further emphasize the utility of rodent grooming as a reliable measure of repetitive behavior in neuropsychiatric models, holding promise for translational psychiatry. Herein, we mainly focus on rodent self-grooming. Allogrooming (grooming being applied on one animal by its conspecifics via licking or carefully nibbling) and heterogrooming (a form of grooming behavior directing towards another animal, which occurs in other contexts, such as maternal, sexual, aggressive, or social behaviors) are not covered due to space constraints.