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Giachello, C. N. G.

Publications and source records attributed to Giachello, C. N. G..

2 recordsLinked to original sources

Motor circuit function is stabilized during postembryonic growth by anterograde trans-synaptic Jelly Belly - Anaplastic Lymphoma Kinase signaling

The brain adapts to a changing environment or growing body size by structural growth and synaptic plasticity. Mechanisms studied to date promote synaptic growth between partner neurons, while negative counterparts that inhibit such interactions have so far remained elusive. Here, we investigate the role of Jeb-Alk signaling in coordinating motor circuit growth during larval stages of Drosophila. We quantify neuronal growth dynamics by intra-vital imaging, and synaptogenesis at nanometer resolution using endogenously labeled synaptic proteins, conditionally tagged with a fluorophore, and link changes in circuit anatomy with altered synaptic physiology and behavior. We find that loss of Jeb-Alk signaling leads to increased strengthening of synaptic excitation by developmental addition of additional postsynaptic but not pre-synaptic specializations. These changes ultimately lead to an epilepsy-like seizure behavior. We thus demonstrate that trans-synaptic anterograde Jeb-Alk signaling acts to stabilize developmental plasticity and circuit function, and that it does so specifically during postembryonic growth.

neuroscience

Activity manipulation of an excitatory interneuron, during an embryonic critical period, alters network tuning of the Drosophila larval locomotor circuit

As nervous systems develop, activity perturbations during critical periods can lead to permanently altered network function. However, how activity perturbation influences individual synapses, the network response and the underlying signalling mechanisms are not well understood. Here, we exploit a recently identified critical period in the development of the Drosophila larval locomotor circuit to show that activity perturbation differentially affects individual and identified synaptic pairings. Remarkably, we further show that activity-manipulation of a selective excitatory interneuron is sufficient to fully recapitulate the effects induced by network-wide activity disturbance; indicative that some neurons make a greater contribution to network tuning. We identify nitric oxide (NO)-signalling as a potential mediator of activity-dependent network tuning during the critical period. Significantly, the effect of NO-signalling to network tuning is dictated by the prior activity state of the network. Thus, this study provides mechanistic insight that is currently lacking into how activity during a critical period tunes a developing network.

neuroscience