Investigating the Recruitment of Parvalbumin and Somatostatin Interneurons into Engrams for Associative Recognition Memory

Abstract

The panic of losing your car in the carpark captures the importance of associative recognition memory: the ability to identify something as familiar, along with where and when it was seen. Effectively modelled through object-in-place (OIP) tasks, associative recognition memory is demonstrated by the time mice spend exploring novel vs familiar objects and configurations. However, the neuronal networks underpinning this memory are only just being identified. During learning, neurons are recruited into ensembles called engrams, the neural representation of memories. Interneurons, especially parvalbumin- (PV+) and somatostatin- (SOM+) expressing, are essential in regulating network activity and memory formation, but their contributions to associative recognition memory are little understood. Active cells within the medial prefrontal cortex (mPFC) expressed TdTomato (TdTom+) via Targeted Recombination of Active Populations (TRAP) technology and were visualised following OiP and a range of control tasks. Cell numbers, and the overlap between TdTom+/PV+ or TdTom+/SOM+, were quantified and compared across conditions. Experiment 1 demonstrated no effect of behavioural condition on PV+ or SOM+ interneuron recruitment into engrams for associative recognition memory, but PV+ interneuron recruitment displayed a trend to decrease in OiP learning; while SOM+ interneurons were recruited to a larger extent than PV+ despite being less prevalent. Experiment 2 explored the effect of inhibiting hippocampal (HPC) NMDA receptors on the recruitment of PV+ and SOM+ interneurons in the mPFC during associative recognition learning. AP5 infusion had no effect on PV+ or SOM+ interneuron recruitment, but did result an overall increase in total engram cell numbers, and did impair OiP task performance. These results support theories of engram sparsity, supporting an activity-dependent organisation of mPFC engrams, influenced by HPC glutamatergic output onto interneurons in the mPFC.

Date of Award	20 Jan 2026
Original language	English
Awarding Institution	University of Bristol
Supervisor	Gareth R I Barker (Supervisor) & Elizabeth Warburton (Supervisor)