Description of the thesis topic

Neuronal ensembles population dynamics in the nucleus reunines of the thalamus mediating attenuation of traumatic memories

Background and Rationale

Fear is an essential emotion for survival that can generate some of the most robust forms of memory. Because of this characteristic, fear can also generate some of the most harmful memories, namely when fear is experienced excessively and repeatedly. Then, fearful memories become maladaptive, resulting in post-traumatic stress disorder (PTSD) and anxiety-related disorders.
Remarkably, despite the high prevalence of such disorders, effective treatment options for traumatic memories remain scarce. The primary measures against trauma-related disorders are based on a form of behavioral psychotherapy called exposure therapy, which however loses efficacy as time elapses from the experience of the traumatic event. This significantly reduces its applicability for PTSD, as in most cases traumatic memories do not develop shortly after the trauma, but with delay. Despite this evidence, the majority of studies aimed at unravelling the neural substrates of fear attenuation have focused on recent traumatic memories, leaving fear attenuation brain networks at remote timepoints unexplored. In order to pave the way for effective interventions against long-lasting PTSD, it is of prime importance to understand the neuronal and molecular mechanisms at the basis of remote fear memory attenuation.
Using a behavioural paradigm to study the extinction of remote traumatic memory in mice, we have recently discovered that neuronal activity at the level of the nucleus reuniens (NRe) of the thalamus is crucial for attenuation of remote (1-month old) traumatic memory.
While this finding provides the first insight into the brain substrates of remote fear memory attenuation, the neurophysiological mechanisms at the basis of this process are far from being unravelled. In particular:

1. The functional connectivity of the NRe mediating fear attenuation is not known.
2. The population coding mediating the specific attenuation of selected fear memories remains unexplored.

Objectives and methodologies

1. Interrogation of the functional partners of the NRe in remote fear memory attenuation.

In order to unravel the brain network interacting with the NRe to efficiently attenuate remote fear memory, the candidate will functionally map the input-output connections of the NRe during experimental fear extinction. To this end, the PhD candidate will use a combination of viral tracing tools and cFos-based brain wide activity mapping to dissect the specific NRe-centered neural pathways recruited upon efficient fear extinction. Based on such unbiased functional connectivity screening, the candidate will identify extinction-activated NRe input-output pathways and analyse their real-time activity with high temporal resolution by in-vivo fiber photometry.

2. Identify and characterize the neural ensembles within the NRe mediating remote fear memory attenuation

After having anatomically and functionally described such NRe input-output circuits, the candidate will investigate the neuronal activity population coding within the NRe underlying fear attenuation. For this, the candidate will perform single neurons activity recordings in freely moving animals undergoing remote fear memory extinction using miniaturised head implanted fluorescent microscopes (miniscopes). In this experimental setting, large-scale neuronal activity can be continuously monitored in relation to the on-line fear state of the animal at the single cell resolution. This study will this lead to the first identification of the specific thalamic ensembles that encode high and low fear states during remote fear memory extinction and follow their evolution over the course of fear attenuation.

Work Context

The position is funded by an ERCStG Ethofearless grant. The project is led by Dr Bianca A. Silva. Our team is part of the Institut de Pharmacologie Moléculaire et Cellulaire (www.ipmc.cnrs.fr), a joint public research institute of the CNRS, INSERM and the Université Côte d'Azur. The Institute is located in Sophia Antipolis, a technology park on the outskirts of Nice that is home to numerous biotechnology and healthcare companies offering a dynamic environment for scientific research.
Preferred candidate profile:
Master's degree in: neuroscience, biology, computer science, physics, mathematics, engineering.
Experience in: programming (preferably Python, R)
Experience in mouse behavior, circuit neuroscience, mouse surgery is a plus.
The position is located in a sector covered by the Protection of Scientific and Technical Potential (PPST), and therefore requires, in accordance with regulations, that your arrival be authorized by the competent MESR authority.

The position is located in a sector under the protection of scientific and technical potential (PPST), and therefore requires, in accordance with the regulations, that your arrival is authorized by the competent authority of the MESR.

Constraints and risks

The constraints of this position are linked to the handling of animals. Candidates must not be allergic to rodents. Candidates may be required to be on call at weekends to supervise the animals. Possible risks include animal bites and cuts from handling the microtome.