Developmental Mechanisms of Motor Network Tuning (360G-Wellcome-217099_A_19_Z)

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 At early stages activity is spontaneously generated, and then superseded by patterned network activity as sensory afferents become active.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.