Role of perineuronal net degradation by activated microglia in the retrospenial cortex in neuropathic pain

Neuropathic pain affects around 10% of the population worldwide and despite years of research remains difficult to treat. It has been recently suggested that the degradation of a component of the extracellular matrix, the perineuronal net (PNN) surrounding neurons, by activated microglia at the spinal cord level could played a crucial role in neuropathic pain. We demonstrated that the retrosplenial cortex could play an important role in neuropathic pain (Barriere et al, 2019) and, importantly, that the perineuronal net is also degraded by activated microglia. However, the type of neurones (inhibitory or excitatory) and the consequences of this degradation on neuronal activity and synaptic structure are not known as well as the effect of local microglia inhibition on this brain structure on neuropathic pain. Our aim is to better characterize the degradation of the perineuronal net and the type of neurons particularly affected as well as synapses engulfment by microglia in the retrospenial cortex in a neuropathic pain model. Therefore, we will investigate the type of neurons, their synaptic structure as well as the effect of microglia inhibition within the retrosplenial cortex on PNN degradation, neuronal activity using in vivo fiber photometry and behavioural tests to assess pain and associated comorbidities in a neuropathic pain context. To do so, we will use several approaches ranging from behavioural tests, local chemogenetic inhibition of microglia, fiber photometry and immunochemistry/RNAscope. This project should help to better understand the role of the perineuronal net and microglia within the retrosplenial cortex in neuropathic pain.

The candidate must have a Master’s degree or equivalent. They must have an overall average of at least 12/20 and be ranked in the top half of their Master’s class.
Knowledge of neuroscience/pharmacology is essential.
Experience in behavioural techniques and/or immunohistochemistry would be an advantage.