■ Functional Ultrasound imaging of BDNF’s cortical functions in pain perception in health and disease

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Description of the PhD project

Our team is studying the mechanisms of cortical plasticity that underlies the sensory or emotional aspect of pain. In collaboration with M. Tanter, who developed functional ultrasound imaging (fUS,1,2), we are characterizing the alteration of brain networks using multimodal imaging (functional activations and functional connectivity3). We previously showed that this technique, with an outstanding spatial and temporal resolution4,5, can be adapted for the imaging of freely moving animals6.

In this project we intend to fill the gap between network communication between brain structures, assessed with fUS imaging and the local modification of neuronal plasticity at the molecular level. One of the most promising molecular target related to plasticity associated with the transformation of acute to chronic pain is BDNF (Brain-Derived Neurotrophic Factor), which, in normal conditions, participates in learning and memory7. While the role of BDNF has been established in the spinal cord in both inflammatory and neuropathic pain, its role is unknown at the level of the brain.

The aim of this PhD is to i) identify the main forms of BDNF expressed in the ‘pain matrix’ in conditions of chronic pain and ii) study the role of these forms of BDNF on the alterations of brain network in animal models of persistent pain, using functional ultrasound imaging in freely moving and behaving animals.

This transdisciplinary PhD will be performed at the edge of Neuroscience and acoustical physic-based Biomedical Imaging. It will involve the use of bio-compatible micro-bubbles for the enhancement of sensitivity and of micro-electronics at the required miniaturisation for freely moving behaving animals. This project will be directed by Dr Sophie Pezet (Brain Plasticity Unit, https://www.bio.espci.fr/-Sophie-Pezet-Douleur-et-Adaptation-Neurale) who has extensive experience and deep expertise in the pain field and who participated to the development of fUS in rodents. This work will be carried out in collaboration with Dr Mickael Tanter (Institut Langevin), who is a world leader in ultrasound imaging and creator of two start-ups linked to fUS imaging. Due to the transdisciplinary nature of this project, the applicant would ideally have a dual knowledge of Neuroscience and signal analysis.

1. Mace, E. et al.. Nat Methods 8, 662–664 (2011).
2. Mace, E. et al. IEEE Trans. Ultrason. Ferroelectr. Freq. Control 60, 492–506 (2013).
3. Osmanski, B.-F.et al., Nat. Commun. 5, 5023 (2014).
4. Errico, C. et al. Neuroimage 124, 752–761 (2016).
5. Errico, C. et al. Nature 527, 499–502 (2015).
6. Tiran, E. et al. Ultrasound Med. Biol. 43, 1679–1689 (2017).
7. Lu, B. Learn. Mem. 10, 86–98 (2003).


Neuroscience – Neuroimaging – Plasticity – Brain – Pain – Ultrasound – Physics – BDNF – Neuromodulator

Research unit

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 5 teams, interested by the study of the molecular, cellular, anatomical and behavioral mechanisms of neuroplasticity. This theme is addressed by an integrated multidisciplinary approach, combining genetics, molecular and cellular biology, neural network studies, brain imaging, physiology and behavior.

Our laboratory brings together researchers interested in understanding the functioning of the brain at different scales, in order to develop collaborations and synergies. Complementary biological models are studied: Drosophila (Thomas Preat’s team and Serge Birman’s team), rodents (Karim Benchenane’s team and Sophie Pezet’s team), a team is working on Human (François Vialatte’s team). Two of the teams have been award 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
Sophie Pezet

3i Aspects of the proposal

This project is a novel and innovative transdisciplinary project between the fields of Neuroscience and Physics. It will be undertaken by two teams that have been fruitfully collaborating over the last 4 years: Team ‘Pain and Neural Adaptation’ (Laboratory of Brain Plasticity, PI S. Pezet) and the laboratory of Ultrasound for Medicine (Institut Langevin, PI M. Tanter). Bringing their respective expertise in Neuroscience and animal Physiology (for SP), but also wave Physics and signal analysis (for MT), both teams collaborated on an everyday basis towards the technological development of new imaging modalities of functional ultrasound imaging in the rodent brain. The accomplishments were the imaging of functional connectivity (that measures indirectly the properties of neuronal networks) with high spatial and temporal resolution 5. Coupled to bio-compatible micro-bubbles, the imaging of the rat brain was improved further by reducing its invasiveness 6. This approach enabled us to further increase the spatial resolution of fUS imaging, allowing imaging in the live rat using super-localization (10um) resolution 7. Finally, the teams showed that this versatile technique allows imaging in freely moving animals 8. We are currently using it for the study of altered brain functions associated with chronic pain diseases.

Several years ago, Mickael Tanter developed a revolutionary approach to study haemodynamic changes in biological tissues. Using tilted planar waves, this neuroimaging approach can image changes in Doppler signal with remarkable spatial (100um) and temporal (0.2ms) resolution. The development of this technique enabled the creation of two start-ups: Supersonics that develops ultrasound imagers, and Neuroflows that develops set-ups for the brain imaging in rodents. Several development initiated in rodents led to human applications as its recent use to image infants brain both in normal and abnormal condition 8,9. The potential for innovations is also important in rodents as it paves the way to an unmatched ability to image the rodent brain. Using bio-compatible micro-bubbles, our teams enhanced even further the spatial resolution of this technique (10um)7. All these transdisciplinary developments will be used for fondamental research in rodent and for the improvement of fUS for human applcation, which will have naturally a positive impact on Neuroflows. Many aspects developed in the proposed research project will be of high interest such as the micro-technology required for the miniatirisation in freely moving experiments that is crucial for the portability of the device in clinical use. Altogether, our technological achievements will foster innovation in the company. Finally, as our research will provide new mechanisms underlying chronic pain and approach to eveluate the transition from acute to chronic pain, our project will of high interest to pharmaceutical companies (such as Roche who contacted us) for the development of new treatments for chronic pain.

Our project has a strong international attractivity because fUS imaging was invented and developed at the ESPCI. Only 3 centers in the world possess such technology. Due to the attractability of this technique, it allowed publications in high impact factor journals. Our laboratory has a strong attractivity, as 20% of our students are foreign students. Our laboratory routinely recruits foreign students, via the ‘Ecole des Neurosciences de Paris’, that is a worldwide recognized organisation that recruits high caliber Neuroscience students throughout the world. The applicant should have carried out a part of his/her studies outside of France. The integration in the laboratory of Brain plasticity will therefore be an international mobility. S. Pezet has a close relationship with Prof. SB McMahon in London (King’s College London). It is planned that during the course of this project, the PhD student will visit Prof. McMahon’s laboratory for crucial parts.

Expected Profile of the candidate

Due to the transdisciplinary nature of this project, the applicant would ideally have a dual knowledge of Neuroscience and signal analysis.
Knowledge in programming (Matlab) would be appreciated.

10 Rue Vauquelin, 75005 Paris