Project ID NS-MH2023_24

ThemeNS-MH

Co Supervisor 1A IoPPN/Centre for Developmental NeurobiologyWebsite

Co Supervisor 1B IoPPN/Centre for Developmental NeurobiologyWebsite

How does plasticity in target interneurons influence functional recovery during naturally occurring neuronal regeneration?

The adult mammalian brain is generally terrible at repairing itself, but some specialised regions can do it naturally. This project will leverage the unique regenerative ability of the olfactory system to ask how neuronal plasticity can influence functional recovery from injury. Our aim is to identify mechanisms that promote successful neuronal regeneration in a natural setting, so that these or similar processes can be used to encourage better recovery in parts of the nervous system that do not usually repair themselves well.

We will focus on plasticity in a population of olfactory bulb interneurons that is crucial for regulating sensory information flow from nose to cortex. Our previous work has found that these cells are extremely plastic in response to brief alterations in sensory experience. However, we do not know how they respond to longer-term changes caused by olfactory bulb denervation and subsequent re-innervation. Years 1 and 2 of the PhD project will therefore use acute slice electrophysiology (Grubb lab) and in vivo 2-photon functional imaging (Khan lab) to uncover the plastic processes occurring in a specific class of inhibitory interneurons during the regeneration of their sensory neuron inputs. Rotation projects will involve training and initial recordings in the acute slice model.

In Year 3 we will then ask how these plastic processes influence functional recovery after injury. We will use chemogenetics to control plasticity in olfactory bulb interneurons, and will use functional and behavioural readouts to assess how interneuron plasticity influences the natural regeneration of sensory processing.

One representative publication from each co-supervisor:

Galliano E, Hahn C, Browne L, Rodriguez Villamayor P, Tufo C, Crespo A, Grubb MS (2021) Brief sensory deprivation triggers cell type-specific structural and functional plasticity in olfactory bulb neurons. J Neurosci, 41:2135-51. https://doi.org/10.1523/JNEUROSCI.1606-20.2020

Poort, J., Wilmes K., Blot, A., Chadwick A., Sahani, M., Clopath C., Mrsic-Flogel, T.D., Hofer, S.B., Khan, A.G. (2022). Learning and attention increase visual response selectivity through distinct mechanisms. Neuron 110(4):686-697