How do interneurons shape the maturation of hippocampal circuits?

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The aim of the internship is to probe the functional and anatomical organization and maturation of hippocampal CA1 GABAergic networks during early postnatal development.



The team is investigating the role of early neuronal activity on the organization of mature neuronal networks with a specific focus on the hippocampus. The hippocampus is a brain region which supports episodic memory and spatial navigation. One unsolved question is to understand how hippocampal activity emerges during development.
To characterize early network activity in the hippocampus we designed an experimental approach (see figure below) that enables us to perform both in-vivo two-photon calcium imaging at early stages of development (starting on the first postnatal week) and behavioral recordings. This approach allows us to describe the maturation of neuronal activity at the network level and to link it to the animal behavior.
As described in previous studies, during early stages of development (first postnatal week), myoclonic twitches (involuntary brief muscle contraction) trigger synchronous waves of neuronal activity in the developing hippocampus. Later during development (around the second postnatal week), we found that neuronal activity tends to be less synchronous and independent from movement of the animal.
Interestingly, this “internalization” of the activity is also accompanied by a maturation of perisomatic GABAergic interneurons that abruptly extend their axons. Interneurons are known to play crucial roles in the maturation of neuronal networks in multiple cortical regions. Previous in-vitro experiments have shown that a specific population of interneurons (so called hub neurons) were able to synchronize the activity of hundreds of neurons in the hippocampus. However, the precise role of GABAergic neurons in shaping in-vivo neuronal activity in the region CA1 of the hippocampus remains unknown.

The project we propose:

One first challenge resides in the characterization of neuronal activity at population level in the hippocampus during early development (2 first postnatal weeks). The aim of the internship is to probe the functional and anatomical organization and maturation of hippocampal CA1 GABAergic networks during early postnatal development.
In collaboration with other team members, the student will use a combination of transgenic mice, virus injections, and state of the art in vivo two-photon imaging (see figure below) to either specifically image only GABAergic neurons or image all neuronal populations with the ability to identify GABAergic neurons among them. We will benefit from a newly deep-learning based algorithm (developed in the team, see Denis et al., 2020) to analyze these recordings and characterize neuronal activity. To complement this functional characterization of developing GABAergic networks the student will investigate the maturation of the circuit with an anatomical approach. To do so the student will perform trans-synaptic retrograde labelling in order to map the inputs that CA1 GABAergic neurons receive.
This project offers the opportunity to familiarize with anatomical/tracing experiments, state of the art in vivo imaging, as well as calcium imaging data processing and analysis using a deep learning approach.

Desired profile

We are looking for a creative, motivated candidate with strong interest in Neuroscience at circuit level. No particular background is required but some knowledge in two-photon calcium imaging and/or electrophysiological recordings and/or computational analysis would be a plus.

Host institution

Our lab in a few words:

The student will be directly supervised by Michel Picardo (Principal Investigator) and collaborate with other PhD students. We are a Team, working all together and having a lot of fun. Come as you are and shoot for the moon you may land in the brain with blinking neurons…

The institute and the city:
INMED is an excellent academic environment where the opportunities for collaboration abound with a large and outstanding neuroscience faculty. Marseille offers all the advantages of any large city, together with the amazing sea and sun of south of France (Provence).

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