Perineuronal nets in cognition and behaviour This behavioural and integrative neuroscience project in rats will examine the role of prefrontal and hippocampal perineuronal nets (PNNs) in cognition and behaviour. Perineuronal nets (PNNs) are extracellular matrix structures surrounding neurons in the mammalian central nervous system. They have been implicated in cognitive and behavioural functions, and disruption of PNNs has been associated with neuropsychiatric disorders, including schizophrenia (Beretta et al., 2015, Schizophr Res 167(1-3), 18-27; Fawcett et al., 2019, Nature Rev Neurosci 20(8), 451-465).
This project will focus on the prefrontal cortex and hippocampus, where PNNs mainly surround inhibitory GABA interneurons. There is substantial evidence that PNNs are important for inhibitory GABA function (Beretta et al., 2015; Fawcett et al., 2019; Wingert and Sorg, 2021, Front Synaptic Neurosci 13, doi:10.3389/fnsyn.2021.673210). Therefore, we will test the idea that PNNs are important for neural, cognitive and behavioural functions associated with prefrontal and hippocampal inhibitory GABA function (Bast et al., 2017, Br J Pharmacol 174(19), 3211-3225) (Aim 1). Moreover, many factors implicated in schizophrenia pathophysiology, including NMDA receptor hypofunction (Cadinu et al.,2018, Neuropharmacology 142, 41-62), have been linked to disruption of both PNNs and GABAergic interneurons, particularly in prefrontal cortex and hippocampus (Steullet et al., 2017, Mol Psychiatry 22(7), 936-943). We will examine the relationship between NMDA receptor hypofunction, integrity of prefrontal and hippocampal PNNs and GABAergic interneurons, and cognitive and behavioural changes (Aim 2).
The student will combine brain site-specific disruption of PNNs (by local microinjection of the enzyme chondroitinase ABC, e.g. Shah and Lodge, 2013, Transl Psychiatry 3(1), e215; Paylor et al., 2018, eNeuro, doi:10.1523/ENEURO.0253-18.2018) (Aim 1) and the subchronic phencyclidine model of NMDA receptor hypofunction (Cadinu et al., 2018, Neuropharmacology) (Aim 2) in combination with behavioural tests, in vivo electrophysiology and ex vivo histological methods in rats, similar to our previous studies (e.g., Pezze et al., 2014, J Neurosci 34(23), 7931-7946; McGarrity et al., 2017, Cereb Cortex 27(9), 4447-4462; Harte et al., 2007, J Neural Transmission 114(7), 893-898; Gigg et al., 2020, J Psychopharmacology 34(1), 115-124). The project will be supervised by Tobias Bast and Helen Cassaday (Psychology, University of Nottingham) and Michael Harte and John Gigg (b-neuro at the University of Manchester).
The student will join the Behavioural Neuroscience Group in the School of Psychology at the University of Nottingham and will spend 3-6 months with b-neuro. Any enquiries about the project may be directed to the main supervisor Tobias Bast (tobias.bast@nottingham.ac.uk).
Funding is available for four years from late September 2022. The award covers tuition fee (£4,567) at the home rate plus an annual stipend (£15,840) for 2022. This is set by the Research Councils. UK and international candidates are eligible to apply.