Olfactory adaptation: recordings from the human olfactory epithelium

Purpose Olfactory adaptation is a peripheral (at the epithelium level) or a central (at the brain level) mechanism resulting from repeated or prolonged odorous exposure that can induce a perceptual decrease. The aim of this study was to assess whether a peripheral adaptation occurs when an odor is repeated ten times. Moreover, the specificity of the peripheral adaptation to the nature of the odorant was investigated. Methods Four odorants (eugenol, manzanate, ISO E Super and phenylethanol) were presented using precisely controlled air-dilution olfactometry. They differed in terms of their physicochemical properties. Electrophysiological recordings were made at the level of the olfactory mucosa, the so-called electro-olfactogram (EOG). Thirty-five right-handed participants were recruited. Results Sixty-nine percent of the participants presented at least one EOG, whatever the odor condition. The EOG amplitude did not significantly decrease over 10 repeated exposures to any odorant. The intensity ratings tended to decrease over stimulations for manzanate, PEA, and eugenol. No correlation was found between the mean EOG amplitudes and the mean intensity ratings. However, the presence of EOG amplitude decreases over stimulations for few subjects suggests that peripheral adaptation might exist. Conclusion Overall, our results did not establish a clear peripheral adaptation measured with EOG but indicate the eventuality of such an effect.

Odor response adaptation in Drosophila—a continuous individualization process

Olfactory perception is very individualized in humans and also in Drosophila. The process that individualize olfaction is adaptation that across multiple time scales and mechanisms shape perception and olfactory-guided behaviors. Olfactory adaptation occurs both in the central nervous system and in the periphery. Central adaptation occurs at the level of the circuits that process olfactory inputs from the periphery where it can integrate inputs from other senses, metabolic states, and stress. We will here focus on the periphery and how the fast, slow, and persistent (lifelong) adaptation mechanisms in the olfactory sensory neurons individualize the Drosophila olfactory system.

Mitf links neuronal activity and long-term homeostatic intrinsic plasticity

Neuroplasticity forms the basis for neuronal circuit complexity and can determine differences between otherwise similar circuits. Although synaptic plasticity is fairly well characterized, much less is known about the molecular mechanisms underlying intrinsic plasticity, especially its transcriptional regulation. We show that the Microphthalmia-associated transcription factor (Mitf), best known as the master regulator of melanocytic cell fate and differentiation, plays a central role in homeostatic intrinsic plasticity of olfactory bulb (OB) projection neurons. Mitral and tufted (M/T) neurons from Mitf mutant mice are hyperexcitable due to reduced Type-A potassium current (IA) and they exhibit reduced expression of Kcnd3, which encodes a potassium voltage-gated channel subunit (Kv4.3) important for generating the IA. Furthermore, expression of the Mitf and Kcnd3 genes is activity-dependent in OB projection neurons, The MITF protein binds to and activates expression from Kcnd3 regulatory elements. Activity can therefore affect Kcnd3 expression directly via MITF. Moreover, Mitf mutant mice have changes in olfactory habituation and have increased habitutation for an odourant following long-term exposure, indicating that regulation of Kcnd3 is pivotal for long-term olfactory adaptation. Our findings show that Mitf acts as a direct regulator of intrinsic homeostatic feedback, plays a key role in olfactory adaptation and links neuronal activity, transcriptional changes and neuronal function.Significance statementA direct, Mitf-dependent link between neuronal activity and homeostatic changes in the expression of a key potassium channel subunit is demonstrated in projection neurons of the mouse OB. This is one of the first studies that directly link activity and genetically defined changes in intrinsic plasticity, leading to changes in neuronal response. These findings broaden the general understanding of transcriptional regulation of homeostatic intrinsic plasticity in learning and memory. The results are also important for understanding the role of Mitf in other cell types. Regulation of intrinsic plasticity has wide-ranging implications and fundamental importance for neurological diseases such as neurodegeneration, autism and epilepsy.