SickKids researchers discover precise molecular mechanisms that can influence memory

Learning and memory are crucial parts of human cognition, yet the biological processes that govern how we learn and store different types of memories are poorly understood. Although a cellular process called synaptic plasticity has long been thought to contribute to learning and memory, many of the neural mechanisms behind synaptic plasticity have remained unclear.

In a recently published study entitled The C-terminal tails of endogenous GluA1 and GluA2 differentially contribute to hippocampal synaptic plasticity and learning, researchers from The Hospital for Sick Children (SickKids) have discovered the precise neuronal mechanisms that can regulate synaptic plasticity to influence distinct forms of memory. We sat down with Dr. Zhengping Jia, a Senior Scientist in the Neurosciences & Mental Health Program at SickKids who led the study, published online in Nature Neuroscience.

What is synaptic plasticity?

Synaptic plasticity is the strengthening or weakening of connections between brain nerve cells, or neurons. Each neuron has axons which are long, thread-like parts of the cell that connect to the dendrites of other neurons. The connection between axons and dendrites belonging to different neurons is called a synapse, a highly specialized structure where chemical signals called neurotransmitters release and communicate between neurons.

The receiving dendrite (or post-synaptic membrane) has a number of receptors for different neurotransmitters. The post-synaptic membrane may start out with a certain number of receptors but that number can increase or decrease based on the chemical signals occurring in the brain. This process underlies synaptic plasticity.

What did you find that could regulate synaptic plasticity to have such a distinct impact on memory?

We looked at receptors for glutamate, which is the most prevalent excitatory neurotransmitter in the brain. Specifically, we looked at the receptors GluA1 and GluA2. When we altered part of the receptors called the carboxyl-terminal, or C-terminal, it was enough to impair contextual fear and spatial memory.

We develop contextual fear memory when we come into contact with something or someone in a particular environment or context that scares us. Later on, when we remember that context as being scary we are using the contextual fear memory we developed. We use spatial memory to navigate the world around us and remember where we are in familiar surroundings.
When we disrupted the C-terminal of GluA1, contextual fear memory was intact but spatial learning was no longer functioning. When we disrupted the C-terminal of GluA2, spatial learning was working but contextual fear memory was impaired.

What does this mean for clinicians?

These findings represent a significant advancement in our current understanding of the cellular and molecular mechanisms governing learning and memory. It is the first study to identify a specific domain on native glutamate receptors that enables different forms of neuronal plasticity and memory.

We can potentially intervene in these small specific regions of the receptors to regulate different forms of memory. This could be important to provide a specific target for therapies meant to reverse memory deficit in brain disorders, such as Alzheimer’s disease and autism.

Our next steps will be to examine how this molecular process is altered in neurodevelopmental and neurodegenerative diseases, so that we may be able to correct these alterations and improve memory formation.

Jia is a Professor in the Department of Physiology at the University of Toronto.

The work was supported by the Canadian Institute of Health Research, Canadian National Science and Engineering Research Council, Brain Canada and The Hospital for Sick Children Foundation.

The co-lead authors of the study include Celeste Leung and Zikai Zhou.


The Hospital for Sick Children (SickKids)


Healthcanal Staff
About Healthcanal Staff

HealthCanal Editorial team is a team of high standard writers, who qualified the strict entrance test of Health Canal. The team involves in both topic researching and writting, which are under supervision and controlled by medical doctors of medical team.