Structural circuit plasticity by a neurotrophin with a Toll modifies dopamine-dependent behaviour

SUN, J.; ULIAN-BENITEZ, S.; FORERO, M. G.; LI, G.; SINGH, D.; CACHERO, S.; ROJO-CORTES, F. R.; MOREIRA, M.; KAVANAGH, D.; JEFFERIS, G. S. X. E.; HIDALGO, A.

doi:10.1101/2023.01.04.522695

bioRxiv · 10.1101/2023.01.04.522695

Structural circuit plasticity by a neurotrophin with a Toll modifies dopamine-dependent behaviour

SUN, J.·ULIAN-BENITEZ, S.·FORERO, M. G.·LI, G.·SINGH, D.·CACHERO, S.·ROJO-CORTES, F. R.·MOREIRA, M.·KAVANAGH, D.·JEFFERIS, G. S. X. E.·HIDALGO, A.

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Abstract

Experience shapes the brain, as neural circuits can be modified by neural stimulation or the lack of it. The molecular mechanisms underlying structural circuit plasticity and how plasticity modifies behaviour, are poorly understood. Subjective experience requires dopamine, a neuromodulator that assigns a value to stimuli, and it also controls behaviour, including locomotion, learning and memory. In Drosophila, Toll receptors are ideally placed to translate experience into structural brain change. Toll-6 is expressed in dopaminergic neurons (DANs), raising the intriguing possibility that Toll-6 could regulate structural plasticity in dopaminergic circuits. Drosophila neurotrophin-2 (DNT-2) is the ligand for Toll-6 and Kek-6, but whether it is required for circuit structural plasticity was unknown. Here, we show that DNT-2 expressing neurons connect with DANs, and they modulate each other. Loss of function for DNT-2 or its receptors Toll-6 and kinase-less Trk-like kek-6 caused DAN and synapse loss, impaired dendrite growth and connectivity, decreased synaptic sites and caused locomotion deficits. By contrast, over-expressed DNT-2 increased DAN cell number, dendrite complexity and promoted synaptogenesis. Neuronal activity modified DNT-2, it increased synaptogenesis in DNT-2-positive neurons and DANs, and over-expression of DNT-2 did too. Altering the levels of DNT-2 or Toll-6 also modified dopamine-dependent behaviours, including locomotion and long-term memory. To conclude, a feedback loop involving dopamine and DNT-2 sculpted the circuits engaged, and DNT-2 with Toll-6 and Kek-6 induced structural plasticity in this circuit modifying brain function and behaviour.

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SUN, J., ULIAN-BENITEZ, S., FORERO, M. G., LI, G., SINGH, D., CACHERO, S., ROJO-CORTES, F. R., MOREIRA, M., KAVANAGH, D., JEFFERIS, G. S. X. E., HIDALGO, A.. 2023-01-04. Structural circuit plasticity by a neurotrophin with a Toll modifies dopamine-dependent behaviour. https://doi.org/10.1101/2023.01.04.522695

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