Neuronal circuits and sensory coding

Team - Neuronal circuits and sensory coding

Our brain is constantly undergoing important state changes such as switching between different levels of alertness or attention. At the cellular level, these variations in brain state are characterized by large fluctuations in neuronal activity. At the behavioural level, these variations affect our ability to process and interpret the sensory information that we receive. For example, a person who is falling asleep is less likely to hear and make sense of the sounds around them. Our team aims at understanding the brain circuits responsible for this phenomenon, by focusing on the effects of alertness on the coding of sensory information.

Our brain is composed of tens of billions of neurons which participate in various cognitive functions, including sensory processing. These neurons are highly diverse, and they each have a unique molecular fingerprint, called transcriptome. How do these diverse neurons support the effects of brain state on sensory perception? What is the link between genetic identity and neuronal function in the brain?

Our lab uses functional imaging techniques and in situ transcriptomics to answer these questions. We use in vivo 2-photon calcium imaging in the cerebral cortex to record neuronal responses to sensory stimuli. Simultaneously, we monitor behavioural parameters to estimate alertness. Following these recordings, we explore the transcriptome of the recorded neurons using coppaFISH, a method of in situ transcriptomics, which can read the expression of >100 genes on brain sections at single cell resolution. This pipeline allows us to relate the function of individual cortical neurons to their genetic identity by aligning the same neurons between the two modalities.

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Experimental tools

We combine in vivo recording approaches with single cell transcriptomic tools to investigate the functions of cortical subtypes.

Ex-vivo transcriptomics with coppaFISH

We are using state-of-the-art transcriptomic tools to gain insights into the molecular identity of neurons. Our in situ transcriptomic method, called coppaFISH, is a custom-made and fully open-source method which allows to identify fine neuronal subtypes using in situ single cell gene expression.

Initially used with a set of 72 genes designed for inhibitory subtypes, we now use coppaFISH with an extended panel of 124 genes to explore both excitatory and inhibitory subtypes.

In vivo 2-photon calcium imaging and optogenetics

We use calcium imaging tools to study neuronal function in the mouse cerebral cortex. We typically record thousands of neurons simultaneously, during spontaneous behaviour or sensory stimulation. We use video recording to quantify several behavioural parameters which give us an estimate of alertness and behavioural state.

We couple these recordings with single cell optogenetic stimulation to interrogate the neuronal circuits involved in sensory coding.

Aligning in vivo and ex vivo modalities

A key step in our experimental pipeline is to align cells recorded in vivo to the same cells characterized ex vivo with coppaFISH. For this we are using a point-cloud registration algorithm based on fast Fourier cross-correlation on reconstructed images. Thanks to this method, we first find the best rigid transformation that aligns the two imaging modalities. This is then followed by non-linear transformations to finalize the matching.

Lab life

Living and working in Marseille – Luminy campus

Our lab is very fortunate to be part of Inmed, which is in the Luminy campus, in the middle of the Parc National des Calanques. The institute provides a supportive, welcoming and collaborative environment to work and flourish in research. On top of that, the close surroundings of the lab provides opportunities for many outdoor activities!

SAFE labs initiative

Stephane is a co-founder of SAFE Labs, an initiative that aims to create more aware, fair, and equitable labs.

The lab is actively working to implement all the commitments outlined in the handbook. You can find more information here: SAFE Labs Handbook

Nos publications

A transcriptomic axis predicts state modulation of cortical interneurons.

Bugeon S, Duffield J, Dipoppa M, Ritoux A, Prankerd I, Nicoloutsopoulos D, Orme D, Shinn M, Peng H, Forrest H, Viduolyte A, Reddy CB, Isogai Y, Carandini M, Harris KD

Nature - Jul 2022

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