Formation and Interaction of Neural Networks (FINN)

How do the vast number of distinct neural circuits form and are organized to regulate diverse yet conserved behaviors in different animals? How do environmental factors affect the formation of neural networks during development?

Our main interest is elucidating how early neural activity and neurotransmission coordinate diverse cellular processes(e.g axon growth, synapse formation and synapse elimination) that will define the specific architecture of a neural network. We explore how functionally distinct circuits first emerge during development, how they interact with each other and how these interactions evolve to lead to the formation of a functionally mature neural network.

One major neurotransmitter, acetylcholine, is crucial for the generation and maintenance of early neural activity. We are examining the role of cholinergic signaling on neural network formation in zebrafish, focusing on a highly conserved, major cholinergic system; the habenulo-interpeduncular (Hb-IPN) pathway in the brain. We are investigating how cholinergic signaling during spontaneous early neural activity participates in forming functional neural connections in this system.

We are also currently exploring whether early disturbances in neural activity and neurotransmission by environmental factors (e.g. nicotine) alter the developmental trajectories of this network and affect its function in behaving animals. Nicotine binds highly to cholinergic receptors to specifically perturb cholinergic signaling. Notably, the Hb-IPN pathway has recently emerged as an important circuit in mediating nicotine-related behaviors and understanding how this pathway develops and changes with nicotine exposure could provide insights into the etiology of nicotine addiction.

Our research utilizes various approaches including analyzing single neuron cellular dynamics in vivo by time-lapse imaging to identifying whole brain neural network activity by calcium imaging using light-sheet microscopy.

Future directions

We are currently investigating two questions in our team:

How do neural activity and neurotransmission mediate cellular dynamics (axon terminal elaboration, synaptogenesis) for the proper formation of neural circuits? To address this question, we are using optogenetics and CRISPR-Cas technology to generate mutants that perturb cholinergic signaling to understand how neural activity and neurotransmission contribute to the formation of cellular and functional connections in the Hb-IPN pathway.

What are the neural pathways that functionally interact with the Hb-IPN pathway and how is the network affected by environmental factors? In collaboration with the Laboratoire Jean Perrin, we are carrying out whole brain functional imaging using light-sheet microscopy to identify other areas of the brain that are functionally connected to the Hb-IPN pathway and elucidating how disturbing cholinergic signaling during development by nicotine affect this neural network

Collaborations

  • Raphael Candelier and Georges Debrégeas (Laboratoire Jean Perrin, UPMC, Paris)
  • Erik Duboué and Marnie Halpern (Carnegie Institute, Baltimore, USA)
  • Jean-Marie Mangin and Pascal Legendre (Neuroscience Paris Seine, UPMC, Paris)
  • Claire Wyart (ICM, Paris)