■ Real-time visualization and modulation of spatial codes in the brain during memory consolidation

Description of the PhD project

The study of spatial memory and the brain regions that play a role in this process has been especially important in understanding disease. In fact, atrophy in the hippocampus is an early feature in the progression of Alzheimer disease and people affected show impairment in spatial navigation. Understanding how the brain process and create a spatial representation of the world outside us is expected to inform the development of new treatments.
In the proposed project we want to identify in mice new regions involved in memory consolidation and target specific neuronal circuits to study their involvement in the memory recall.
Memory consolidation is the process that allows the storage of experienced events in the brain. It is well known that this process involves changes in synaptic connectivity between neurons (1, 2). The synaptic rewiring that occurs during memory consolidation redistribute the functional connections between regions, shifting the network hubs to a different configuration (3). At the same time, systems consolidation involves abstraction of gist information from the original episodic representation, leading to a context-independent memory recall (4).
The purpose of this PhD project will be to (A) identify the changes in specific anatomical pathways that underlie the shift in functional connections of the memory trace from recent to remote memory recall, and (B) how this facilitates the transformation of memory from episodic to more schematic/generalized in nature.
Using the functional connectivity network approach that Vetere validated in her last paper (4) combined with the study of anatomical connectivity it will be possible to delineate new pathways of regions that are involved in the memory consolidation. To visualize the real time changes that occur in specific brain regions required to the formation of the spatial representation during and after memory consolidation, a miniaturized microscope (5) will be used.
This approach is necessary to verify how cells known to encode the spatial information, change their activity pattern after memory consolidation. The spatial representation system includes specific cellular types like place cells, head direction cells, grid cells etc. that are located in different brain regions. The functional connectivity of these individual regions changes over time, suggesting that their role in spatial representation changes during memory consolidation.
The proposed project is innovative and unique because it will address for the first time how specific codes in the brain like head directions cells or place cells changes their activity over time. This question can be finally addressed thanks to a new approach that combines optogenetics and long term calcium imaging analysis in behaving mice.

1. Vetere et al, PNAS, 2011,
2. Restivo*, Vetere* et al, JN, 2009
3. Vetere et al, 2017, Neuron
4. Nadel and Moscovitch, Curt Opinion in Neurobiology, 1997
5. Jacob et al, Biorxiv, 2018


Neuroscience – Plasticity – Brain – Optogenetics – Miniaturized microscope – in vivo calcium imaging – memory consolidation – spatial representation system - head direction cells

Research unit

UMR8249 Brain plasticity

Description of the research Unit/subunit

The ‘Brain Plasticity laboratory’ is a Neurobiology Laboratory from the CNRS (Centre National pour la Recherche Scientifique) hosted at the ESPCI. It is composed of 6 teams, interested by the study of the molecular, cellular, anatomical and behavioral mechanisms of plasticity in the brain. This theme is addressed by an integrated multidisciplinary approach, combining genetics, molecular and cellular biology, neural network studies, brain imaging, physiology and behavior.
Vetere Gisella is a newly recruited Professor at ESPCI that will study how information is encoded and stored in the brain of mice. Complementary biological models are studied: Drosophila (Thomas Preat’s team and Serge Birman’s team), rodents (Karim Benchenane’s team, Sophie Pezet’s team and Gisella Vetere’s team) and humans (François Vialatte’s team). Two of the teams have been awarded by ERC grants from the EU and several collaboration exist with industrial partners. The unique situation of the Brain Plasticity laboratory, within ESPCI Paris, allows us to develop unusual and fruitful bridges between neurobiology and physics.

Name of the supervisor
Gisella Vetere (gisella.vetere@espci.fr)

3i Aspects of the proposal

The evolution of the field of neuroscience has been propelled by the advent of novel technological capabilities, and the pace at which these capabilities are being developed has accelerated dramatically in the past decade. The constant collaboration between neuroscientists and engineering research to develop advanced tools for the study of neuronal activity is crucial today.
This interdisciplinary PhD will be performed at the boundary between Neuroscience and Optical Physics. In fact, we will be using advanced optogenetics (using light to control neuronal activity) as well as a new tool in photonics for in vivo calcium imaging (miniaturized head mounted microscope). These tools have been crucial in the discoveries in brain circuitry and neuronal population activity in the past ten years (1,2).
Combining these two technologies, we can begin to answer how population activity changes while manipulating the circuitry underlying a specific cognitive function, such as memory consolidation.
This project will involve collaborations with international institutes for the development and improvement of the miniaturized microscope technology in combination with the optogenetic approach that will allow the silencing/activation of specific neuronal circuits and at the same time the visualization of cell activity.
Due to the interdisciplinary nature of this project, the applicant would ideally have a background of Optics and a strong interest in Neuroscience.
Knowledge in programming (R, Matlab and/or Python) would be appreciated.
Knowledge in 3D print design would also be appreciated.

Boyden, NN, 2015
Gosh et al, Nat Methods, 2011

Expected Profile of the candidate

Due to the interdisciplinary nature of this project, the applicant would ideally have a background of Optics and a strong interest in Neuroscience.
Knowledge in programming (R, Matlab and/or Python) would be appreciated.
Knowledge in 3D print design would also be appreciated.

Important dates

Call for applications : from July 16th to September 17th 2018
Eligibility check results : Late September
3i Committee evaluation results : Late October
Interviews from the shortlisted candidates with the Selection Committee : Mid-December (week of December 10th)
Final results : Late December