Flexible Long-Term Adaptation in Olfactory Sensory Neurons
by Tatsuya Tsukahara
Sensory cues occur in a context: you walk into the kitchen, and you smell pancakes; you walk into a florist store and smell the roses. But as you linger in the kitchen, your perception of the pancakes diminishes. This diminished perception is caused by sensory adaptation, which filters sensory cues that are constant in a given environment. Sensory adaptation is fundamental to the function of all sensory systems. Deficits in sensory adaptation can lead to sensory overload, which is often observed for people with autism spectrum disorder (ASD). How do animals achieve this adaptation? Previous studies have shown that the brain flexibly adapts sensory responses to repetitive stimuli through synaptic mechanisms. In contrast, the olfactory sensory periphery is generally thought to report sensory information stably and faithfully to the brain, except for fast adaptation to highly dynamic stimuli on a timescale of milliseconds to seconds. These observations are consistent with the idea that brain circuits are primarily responsible for adapting to the environment.
In a recent study, we asked if the olfactory sensory neurons (OSNs) in the mouse nose adapt to environmental stimuli over longer timescales, like hours to days. These timescales are ethologically important, since animals like mice typically stay in the same environment over hours, as they rest in a nest or explore for food. There are 1,000 OSN subtypes in mice, each of which expresses a single odorant receptor (OR) from an extremely large gene family. Using single cell RNA-sequencing, we revealed that each of these 1,000 OSN subtypes harbors a distinct transcriptome. OR-specific transcriptomes are largely determined by interactions between ORs and environmental odors and include more than 70 functional genes involved in the process of converting odor-receptor binding to action potentials. The expression of these functional genes systematically co-varies across OSN subtypes, dynamically and coherently changes across environments, and adaptively modifies odor responses.
A model of long-term transcriptional adaptation in olfactory sensory neurons
As an example, the olfactory sensory neuron shown here is rarely activated in the home-cage environment and this low level of activity is converted into a specific pattern of functional gene expression that boosts its odor responses. On the other hand, when the same neuron is highly activated in a novel environment, functional genes show the opposite trend and attenuate odor responses. In this manner, the same neuron can respond differently to the same odor, depending on the environmental context.
Our study demonstrated that peripheral sensory neurons are remarkably flexible and use a transcriptional adaptation to modify their responses based on their activity history. It also suggests a general model in which a transcriptional variation within a single cell type reflects the varying activity histories of individual neurons. Both peripheral and central neurons may use this novel transcriptional mechanism to adapt to changes in their inputs. Given that ASD risk genes include many transcriptional regulators, deficits in transcriptional adaptation could contribute to the sensory abnormalities observed in diseases like ASD.
Tatusya Tsukahara is a Y. Eva Tan Postdoctoral Fellow in the Datta Lab at Harvard Medical School, part of the Tan-Yang Center for Autism Research at Harvard. He is co-first author of the study described, along with David H. Brann, also of the Datta Lab.
Learn more in the original research article:
A transcriptional rheostat couples past activity to future sensory responses.
Tsukahara T, Brann DH, Pashkovski SL, Guitchounts G, Bozza T, Datta SR. Cell. 2021 Dec 22;184(26):6326-6343.e32.