What role do different interneurons in medial prefrontal cortex play in associative recognition memory?
Award Number
BB/X000915/1Status / Stage
ActiveDates
1 January 2023 -31 December 2025
Duration (calculated)
02 years 11 monthsFunder(s)
BBSRC (UKRI)Funding Amount
£681,884.00Funder/Grant study page
BBSRC UKRIContracted Centre
University of BristolPrincipal Investigator
Professor Zafar BashirPI Contact
Z.I.Bashir@bristol.ac.ukPI ORCID
0000-0003-3650-2136WHO Catergories
Understanding Underlying DiseaseDisease Type
Dementia (Unspecified)CPEC Review Info
| Reference ID | 750 |
|---|---|
| Researcher | Reside Team |
| Published | 07/07/2023 |
Data
| Award Number | BB/X000915/1 |
|---|---|
| Status / Stage | Active |
| Start Date | 20230101 |
| End Date | 20251231 |
| Duration (calculated) | 02 years 11 months |
| Funder/Grant study page | BBSRC UKRI |
| Contracted Centre | University of Bristol |
| Funding Amount | £681,884.00 |
Abstract
We have shown in rodents that a brain circuit centered around the medial prefrontal cortex (mPFC) which receives inputs from hippocampus (HPC), nucleus reuniens (NRe) and medial dorsal thalamus (MD) is critical for associative recognition memory. Inputs from HPC and NRe are necessary for encoding and MD is necessary for retrieval of such memories. The mPFC contains different interneuron types but how these contribute to associative memory is unknown. It is also not known whether these interneuron subtypes are differentially driven by inputs from HPC, NRe or MD to bring about encoding and retrieval. Our hypothesis is that different interneuron subtypes receive inputs from either HPC, NRe or MD to bring about the mPFC dynamics necessary for the separate encoding and retrieval phases of associative recognition memory. This hypothesis will be tested through examining 3 objectives: 1. We will test the roles of mPFC parvalbumin, somatostatin and neuron-derived neurotrophic factor interneurons in different phases (encoding and retrieval) of associative recognition memory. This will be achieved using appropriate Cre mouse lines and viral methods to target selective interneurons for silencing by inhibitory opsins during each phase of associative memory. 2. We will next examine whether the inputs from HPC, NRe and MD differentially target the different interneuron types by using mGRASPi to label specific synapses for confocal imaging analyses. 3. We will finally investigate the synaptic and transmitter mechanisms by which inputs from HPC, NRe and MD control the different interneurons in mPFC. This will use optogenetic transduction of the HPC, NRe and MD input regions and in vitro electrophysiological recordings in mPFC from identified subclasses of interneurons. Overall, this program of research will provide a detailed mechanistic insight into how interneurons in mPFC control the encoding and retrieval of associative recognition memory.
Aims
1. We will test the roles of mPFC parvalbumin, somatostatin and neuron-derived neurotrophic factor interneurons in different phases (encoding and retrieval) of associative recognition memory. 2. We will next examine whether the inputs from HPC, NRe and MD differentially target the different interneuron types by using mGRASPi to label specific synapses for confocal imaging analyses. 3. We will finally investigate the synaptic and transmitter mechanisms by which inputs from HPC, NRe and MD control the different interneurons in mPFC.