Completed Brain & Nervous System Psychology & Behaviour

Establishing circuit, neuronal and synaptic mechanisms of associative recognition memory

Funder Wellcome Charity-funded
Recipient organisation University of Bristol
Funding £2.0M
Period Sept 2017 — Sept 2022

In plain English

AI plain-English summary

Every time you recognise a familiar face in a crowd or remember where you parked your car, a network of brain regions must rapidly coordinate its activity—but exactly how they talk to each other, and when, remains unknown. This project tackles a fundamental gap in neuroscience: we know which brain areas are involved in associative recognition memory (the ability to link an object with its location), but we do not know which specific connections between those areas are required for encoding a memory versus retrieving it later, nor which synaptic mechanisms control each stage. The researchers will use a technique that lets them silence specific neural pathways with millisecond precision in rats, combined with recordings from individual neurons and measurements of synaptic changes in brain slices. This is fundamental science. If successful, it will provide the first circuit-level wiring diagram for how associative memories are formed and recalled across the medial temporal lobe, frontal cortex, and thalamus. Understanding these basic mechanisms could eventually inform treatments for memory disorders such as Alzheimer’s disease or amnesia, where associative recognition is often the first cognitive function to decline. But the immediate value lies in establishing principles that may apply broadly across learning and memory systems.

View original technical description
Recognition memory, our ability to discriminate between new and familiar stimuli, is essential for us to lead normal everyday lives. Such memory requires encoding of information about new and familiar objects, the locations where we saw them, and the formation of robust object-location associations for subsequent memory retrieval. Associative recognition memory depends on distinct but highly interconnected brain regions within the medial temporal lobe, frontal cortex and thalamus. But which regions communicate, and when does communication occur, to form memory associations? Are the same regional connections that are necessary for encoding also required for memory retrieval? Which neuronal and which synaptic mechanisms control encoding and which control retrieval? These questions will be answered using temporally-precise, pathway-specific silencing, neuronal recordings and interrogation of synaptic mechanisms across the circuits. Activity-driven Cre-inducible gene expression in the rat, will be used to determine specifically the neuronal ensembles in different brain regions and their connections that are critical for encoding and retrieval of associative memory while ex vivo electrophysiology will reveal the synaptic mechanisms that control neuronal ensembles activated by learning. This work will establish how highly dynamic, synaptically connected neuronal populations enable associative recognition memory formation through local and long-range neural networks.

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Researchers

Zafar Bashir (EPMC Awardee)

Related Research

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Original classification

Investigator Award in Science

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