The ability to discriminate odorants was assessed using the cross-habituation index, and no genotype differences were observed indicating CB1?/?/CB2?/? mice have the ability to discriminate between different odorants (Fig
The ability to discriminate odorants was assessed using the cross-habituation index, and no genotype differences were observed indicating CB1?/?/CB2?/? mice have the ability to discriminate between different odorants (Fig. behaviors assessed from the buried food test and habituation/dishabituation test. Collectively, these data indicate the presence of an endocannabinoid system in the mouse olfactory epithelium. However, unlike in tadpoles, endocannabinoids do not modulate olfaction. Further investigation within the part of endocannabinoids in progenitor cell function in the olfactory epithelium is definitely warranted. tadpoles (Migliarini et al., 2006; Czesnik et al., 2007). Tadpole CB1 receptors are indicated on dendrites of neurons and 2-AG is definitely synthesized in both neurons and glial-like sustentacular cells (Czesnik et al., 2007; Breunig et al., 2010a). To day, an endocannabinoid system has not been explained in the mammalian olfactory epithelium. Endocannabinoids regulate neuronal activity and signaling in the glomeruli through canonical retrograde signaling and pre-synaptic inhibition (Wang et al., 2012). However, endocannabinoids also have a neuromodulatory part in the olfactory bulb and have been implicated in food intake (Di Marzo and Matias, 2005). A potential mechanism underlying sensory control of food intake is definitely modulation of odorant level of sensitivity by endocannabinoids. In humans and other animals, level of sensitivity to and perceptual quality of food odorants are enhanced with food cravings, and decrease with satiety (Berg et al., 1963; Crumpton et al., 1967; Aime et al., 2007). In addition, dysfunction of the olfactory system happens in eating-related obesity in humans (Richardson et al., 2004). Clearly, the sense of smell may be important in regulating food intake, and metabolic signals such as endocannabinoids may be able BMS-690514 to modulate olfactory functions. Soria-Gomez and colleagues (2014) shown that CB1 receptor activity in the olfactory bulb influences neuronal activation, odorant detection, and food intake in fasted mice. A behavioral assay rating exploration time of increasing concentrations BMS-690514 of an odorant (almond or banana) was used to show cannabinoid treatment (via direct injection into the olfactory bulb or improved AEA production) decreased the odorant concentration at which mice spent significant occasions exploring compared to vehicle treated mice (Soria-Gomez et al., 2014). Additionally, olfactory bulb specific CB1-receptor deficient mice displayed a physiological decrease in odorant detection threshold under vehicle conditions, suggesting that improved odorant detection inside a fasted state is definitely CB1 receptor-specific (Soria-Gomez et al., 2014). Mice having a selective CB1-receptor deficiency in the granule cell coating of the olfactory bulb ate less food 24 hours after fasting than fasted control mice (Soria-Gomez et al., 2014). Collectively, these data suggest that endocannabinoid signaling via CB1 receptors helps link the physiological state of food cravings to odorant detection thresholds and food intake. The peripheral olfactory epithelium is the site where odorants are recognized (odorant threshold) and the central olfactory constructions, the olfactory bulb and olfactory cortex, are involved in the identification and the discrimination of odorants (Enwere et al., 2004; Kovacs, 2004). The cannabinoid system modulates odorant-evoked reactions in the peripheral olfactory epithelium in larval (Czesnik et al., 2007; Breunig et al., 2010a). Odorant threshold level of sensitivity is improved when 2-AG synthetic enzyme diacylglycerol lipase (DAGL) is definitely inhibited pharmacologically, suggesting that endogenous olfactory sensory neuron odorant Rabbit polyclonal to CaMK2 alpha-beta-delta.CaMK2-alpha a protein kinase of the CAMK2 family.A prominent kinase in the central nervous system that may function in long-term potentiation and neurotransmitter release. level of sensitivity is mediated from the endocannabinoid 2-AG (Breunig et al., 2010b). Exogenous cannabinoid activation after fasting decreases odorant threshold, therefore enhancing odorant detection (Breunig et al., 2010b), suggesting a role in food intake. The mouse olfactory epithelium is definitely pseudostratified and contains multiple cell types. Olfactory sensory neurons have a cell soma located in the middle third of the epithelium and an unmyelinated axon that projects to the olfactory bulb. Non-neuronal sustentacular cells and microvillous cells have large cell body located in the top third of the epithelium and thin cytoplasmic extensions that terminate in an endfoot process. Globose basal cells and horizontal basal cells are proliferative multipotent progenitor cells that lay near the basal lamina and give rise to both olfactory sensory neurons and non-neuronal cells (Holbrook et al., 1995; Huard et al., 1998; Chen et al., 2004). These progenitor basal cells proliferate, differentiate and mature to keep up homeostasis in the olfactory epithelium throughout existence. The regulatory mechanisms of olfactory epithelium cells BMS-690514 homeostasis have not been clearly elucidated. In the adult nervous system, the endocannabinoid system regulates progenitor stem cells in restricted neurogenic areas including the subventricular zone and dentate gyrus. Progenitor cell function is definitely inhibited in CB receptor-deficient mice in these mind areas (Jin et al., 2004; Aguado et al., 2005). It is not known if endocannabinoids also regulate olfactory epithelium cells homeostasis. CB receptor-mediated rules of progenitor/stem cell number and fate could have practical and behavioral effects for mice lacking these.