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UK funding (£512,169): Role of morphologically and developmentally diverse dopaminergic neurons in olfactory circuit processing Ukri1 Jan 2023 UK Research and Innovation, United Kingdom
Overview
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Role of morphologically and developmentally diverse dopaminergic neurons in olfactory circuit processing
| Abstract | The brain of mammals, humans included, consists of highly interconnected networks of cells called neurons. Neurons communicate with each other by producing small electrical currents, which they send to other neurons at specialized connection hubs called synapses. Synaptic communication forms the basis of information transfer, and allows the brain to compute inputs coming from the environment (such as smells) and to transform them into appropriate behaviours (such as foraging for food, or avoiding toxic substances). Contrary to other cells such as those in the skin, which are continuously produced and replaced, neurons are born only during the animal's embryonic development. They then form and refine the appropriate synaptic connections, and stay in place for the entire lifespan. This narrow time window to generate neurons means that the brain cannot repair itself in adulthood following injury. On the other hand, this fixed developmental period has the advantage of providing a stable framework of cells, networks and synaptic connections that will be instrumental to process information in a consistent way. However, as it is often the case in biology, this general rule has exceptions: three types of neurons have the ability to be continuously generated during the animal's lifetime. One class of these "rule-breaking" neurons are called dopaminergic and are located in the olfactory bulb, one of the key brain areas that encode smells. Up until recently scientists believed that all bulbar dopaminergic neurons were capable of lifelong generation, but recent evidence has demonstrated that this is not the case. Indeed, two classes of dopaminergic neurons co-exist in the olfactory bulb: the "rule-breaker" ones who can be generated throughout life and are quite small, and the "rule-follower" ones which are born only during the animal's embryonic development and are fairly large. What do these two subtypes of dopaminergic neurons do? This project will answer this question by looking at (1) which other neurons in the smell network send information via synapses to the subtypes of dopaminergic neurons; (2) which other neurons in the smell network receive information via synapses from the subtypes of dopaminergic neurons; (3) what is the effect of the two subtypes of dopaminergic neurons on the animal's ability to process and respond to smells. Our hypothesis is that the small dopaminergic neurons capable of being born during the lifespan of the animals are connected via synapses with few close neighbours, and contribute to the animal's sensitivity to smells - for example, the ability to distinguish between a lot of menthol odour coming from a fresh mint tea, versus a little menthol odour coming from a chewing gum. On the other hand we predict that the large dopaminergic cells born during embryonic development, and which stably persist throughout the animals' life, make many synaptic connections with a large number of near and far neighbouring neurons in the olfactory network. At the behavioural level, we believe that these far-reaching and developmentally-stable dopaminergic neurons facilitate the animal's ability to discriminate different smells - for example, the ability to distinguish between a fresh mint tea and a coffee. These results will be of interest to neuroscientists working on olfaction, neurons development and cell diversity, as well as to clinicians working on disorders involving the sense of smell (including Covid19). Moreover, by studying a population of neurons in the olfactory areas that can regenerate throughout life (which, as mentioned above, is a very rare ability), we will provide valuable insights to translational research that looks into replacing brain cells that have degenerated with functional ones. |
| Category | Research Grant |
| Reference | BB/W014688/1 |
| Status | Active |
| Funded period start | 01/01/2023 |
| Funded period end | 01/09/2026 |
| Funded value | £512,169.00 |
| Source | https://gtr.ukri.org/projects?ref=BB%2FW014688%2F1 |
Participating Organisations
| University of Cambridge | |
| University of Iceland |
The filing refers to a past date, and does not necessarily reflect the current state. The current state is available on the following page: University of Cambridge, Cambridge.
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