Corticothalamic interactions in associate recognition memory

Abstract

Associative recognition memory is the ability to make judgements about the prior occurrence of a stimulus within a spatial and temporal context. There is a critical role for the medial prefrontal cortex (mPFC) and the mediodorsal thalamus (MD) in supporting associative recognition memory in rodents. The MD is considered crucial for supporting associative recognition memory retrieval and requires incoming information from the mPFC during this time for successful retrieval to occur. Whilst cholinergic transmission has been studied in the mPFC during memory encoding and retrieval, its role in the MD during retrieval is unknown. There is also much to be understood regarding the properties of MD neurons, how they respond to incoming signals from the mPFC, and the properties of the mPFC - MD synapse. The projections from the mPFC to the MD are glutamatergic but it is not understood how N-methyl-D-aspartate receptors (NMDARs) are involved in this transmission or whether NMDARs are involved in plasticity mechanisms between the two brain regions during retrieval.
The experiments in this thesis used a combined in vivo and in vitro experimental approach to explore its objectives. These objectives were to investigate how the MD is modulated by acetylcholine in associative recognition memory retrieval, the properties of MD neurons and the mPFC-MD synapse, and the contribution of NMDARs to the transmission between the mPFC and MD.
This thesis provided the first evidence that α4β2 nicotinic acetylcholine receptors and GluN2A and GluN2C/D containing NMDARs in the MD are required to support associative recognition memory retrieval. Data confirmed that MD neurons exhibit two different firing properties depending on their membrane potential and that the mPFC MD synapse undergoes short term plasticity whereby the response facilitates in a frequency and NMDAR dependent manner.

Date of Award	21 Jun 2022
Original language	English
Awarding Institution	University of Bristol
Supervisor	Zafar I Bashir (Supervisor) & Elizabeth Warburton (Supervisor)