Completed Brain & Nervous System Genetics & Molecular Biology

Developmental Mechanisms of Motor Network Tuning

Funder Wellcome Charity-funded
Associated organisations University of Cambridge · University of Manchester Europe PMC affiliations are not treated as award recipients or mapped locations.
Funding £1.9M
Period Mar 2020 — Apr 2025

In plain English

AI plain-English summary

A fruit fly larva’s motor circuits go permanently wrong if their early spontaneous activity is disrupted—and researchers want to know exactly how that happens. This matters because the same principle likely applies to human brain development. In many animals, including people, neural circuits go through a “critical period” where activity—first spontaneous, then driven by sensory input—shapes how networks wire up. If that activity is abnormal during this window, errors can become locked in, potentially contributing to later neurological disorders. Yet the cellular and molecular details of how circuits tune themselves, and why early disruption causes permanent damage, remain poorly understood. The research uses the fruit fly larva’s motor circuit, which contains identifiable, tractable neurons with known connections. This allows the team to track, at single-cell resolution, how normal tuning occurs and what goes wrong after early activity perturbation. They will also test whether homeostatic mechanisms can compensate for these early errors. This is fundamental science. It will not produce a treatment or device tomorrow. But understanding how developing circuits lock in errors could eventually inform strategies for preventing or reversing miswiring in human neurodevelopmental conditions—much as basic work on critical periods in vision led to insights about amblyopia treatment.

View original technical description
Activity is required for correct development of neural circuits and emergence of appropriate behaviour. At early stages activity is spontaneously generated, and then superseded by patterned network activity as sensory afferents become active. A period of maximal plasticity, termed critical period, generally spans these two phases. Significantly, aberrant activity during neural circuit development, especially when occurring in the critical period, can lead to network errors that become ‘locked in’ and may contribute to neurological disorders in later life. Whilst a requirement for activity is universal for circuit development, important questions remain unanswered. We have identified a comparable requirement for activity in the development of the motor circuit of Drosophila larvae. Notably, perturbation of activity leads to permanent and significant errors in circuit function. This system is composed of identifiable, tractable neurons of defined connectivity. These advantages allow us to study fundamental questions in ways not possible in higher organisms. Exploiting this exceptional level of resolution, our overall goal is: to generate detailed understanding of the cellular and molecular processes that underlie normal network tuning and lead to errors following early activity perturbation; further, to determine in this tractable circuit the capability of homeostatic mechanisms to compensate for early induced perturbations.

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Researchers

Matthias Landgraf (EPMC Awardee)Richard Baines (EPMC Awardee)

Related Research

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Original classification

Investigator Award in Science

Plain English summaries and category classifications on this site are generated by AI and may not perfectly reflect the original research.