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Development of neural circuits in the prefrontal cortex

Periodic Reporting for period 1 - PFCmap (Development of neural circuits in the prefrontal cortex)

Reporting period: 2021-01-01 to 2022-12-31

The aim of the project is to understand the postnatal maturation of the circuitry of the mouse prefrontal cortex. We have chosen to use a range of electrophysiological and anatomical methods to assess this. This question is of fundamental importance to understanding how an important cognitive brain area develops, particularly changes during adolescence. This is of clinical significance because abnormal PFC development is implicated in a wide range of mental health disorders, including schizophrenia and autism. The overall objectives are to measure underlying changes in the properties of PFC circuits at different ages and see if these changes occur during specific periods of development and how these change could bring about improvements in cognitive function as we age.
Since beginning the project we have undertaken a thorough anatomical investigation of the mouse PFC. Looking at synaptic maturation from the first postnatal week (postnatal day (P) 5) until 4 months of age (P120). We have also compared this maturation to another sensory brain area to determine PFC-specific developmental processes. This work is being written up and will be presented at the upcoming British Neuroscience Association Festival in spring 2023. We have also trialled a number of approaches to generate the optogenetic mapping experiments proposed in the original study. We focused on a novel transgenic mouse line, but found the labelling to be insufficient and so will revert to a viral approach. We are now continuing with these experiments to map local connectivity in the developing PFC. This will be facilitated by a PhD student who has been awarded to Dr Anastasiades and Dr Ashby to continue working on this project and has a remaining 2 years of his PhD to run. We aim to have the anatomical data finished by the end of this year and will upload to a preprint server as soon as they are ready. The remaining data will follow in due course.
Although there are no immediate societal implications for this work, it has yielded important information about the maturation of a clinically important brain region that we hope will inspire researchers working in this field. Our findings are already motivating new and exciting experiments within our labs and has cemented further collaborative research between Dr Anastasiades and Dr Ashby.
PFC neurons labeled with optogenetic construct to facilitate local circuit mapping