Regulation of plateau potentials by dendritically targeted inhibitory synaptic transmission.
Award Number
BB/V001728/1Status / Stage
ActiveDates
23 March 2021 -22 March 2024
Duration (calculated)
02 years 11 monthsFunder(s)
BBSRC (UKRI)Funding Amount
£489,840.00Funder/Grant study page
BBSRC UKRIContracted Centre
University of BristolPrincipal Investigator
Professor Jack MellorPI Contact
Jack.Mellor@bristol.ac.ukPI ORCID
0000-0002-7706-8105WHO Catergories
Understanding Underlying DiseaseDisease Type
Dementia (Unspecified)CPEC Review Info
| Reference ID | 731 |
|---|---|
| Researcher | Reside Team |
| Published | 07/07/2023 |
Data
| Award Number | BB/V001728/1 |
|---|---|
| Status / Stage | Active |
| Start Date | 20210323 |
| End Date | 20240322 |
| Duration (calculated) | 02 years 11 months |
| Funder/Grant study page | BBSRC UKRI |
| Contracted Centre | University of Bristol |
| Funding Amount | £489,840.00 |
Abstract
A central function of the brain is its ability to incorporate new information into memories to enable experience-dependent adaptations in behaviour. It is critical that the brain accurately decides which pieces of information should be incorporated and which can be discarded. Underpinning this process is the regulation of memory formation and stability through modulation of synaptic plasticity. As synaptic plasticity is determined by the excitability of post-synaptic neurons, activity of inhibitory synaptic inputs can have a profound impact on synaptic plasticity generation. The aim of this project is to investigate how dendritically targeted OLM inhibitory synaptic inputs regulate excitatory synaptic plasticity and memory formation. We will use the hippocampus of mice where individual excitatory neurons encode aspects of the mouse’s environment in the form of place cells. New information is incorporated into place cells via the formation of plateau potential driven plasticity. Plateau potentials are the result of synchronous excitatory input leading to NMDA receptor activation and large Ca2+ elevations. Plateau potentials are primarily driven by the temporoammonic input to the hippocampus from entorhinal cortex and we have shown that these inputs, and the plateau potentials they generate, can be directly reduced by increases in OLM interneuron activity and inhibitory synapse strength. Therefore, we hypothesise that OLM interneuron activity through modulation of plateau potentials regulates synaptic plasticity within the hippocampus and in doing so controls the formation and stability of place cells. We will address this hypothesis using ex vivo brain slice electrophysiology recordings and Ca2+ imaging of plateau potentials paired with optogenetic stimulation of OLM interneurons. These findings will integrate with in vivo Ca2+ imaging of neuron activity in freely moving mice using head fixed miniscopes to study OLM regulation of place cell stability.
Aims
The aim of this project is to investigate how dendritically targeted OLM inhibitory synaptic inputs regulate excitatory synaptic plasticity and memory formation.