How to Epigenetically Enhance Your Learning and Memory Abilities (KIBRA)

You’ve probably heard of synaptic plasticity before. This important process is key to your ability to learn new things and store new memories.

This is because all the information in your brain is essentially stored in the way that your neurons connect to each other. So, each time you learn a new fact or store a new memory, your neurons have to adjust their connections in order to encode this new information [R, R, R].

In this post, we’re going to be looking at the KIBRA gene – also known as WWC1 – which plays a major role in determining how much synaptic plasticity your brain is capable of, and which can therefore have a significant influence on your overall cognitive function [R]!

Synaptic plasticity is the main process that allows you to learn new things and store new memories.

The KIBRA / WWC1 gene codes for the kidney and brain-expressed (KIBRA) protein. As you can probably guess from its name, it is expressed by the kidneys as well as throughout the brain. It is particularly prominent in brain areas that are involved in learning and memory, such as the PFC and the hippocampus [R, R, R, R].

KIBRA’s primary purpose is to help create AMPA receptors (AMPARs). AMPARs are the main excitatory neurotransmitter receptors in the brain, as well as one of the main brain mechanisms that trigger synaptic plasticity in general [R, R, R, R]. Specifically, these receptors play a central role in triggering long-term potentiation (LTP) and long-term depression (LTD), which are two of the main ways that neurons adjust their connections to each other [R, R, R, R]. This enables them to store new information – and these mechanisms are therefore the primary reason that variants in the KIBRA gene can affect synaptic plasticity, and by extension learning and memory ability [R, R, R, R].

However, KIBRA doesn’t just help create these receptors – it also determines how sensitive you are to the neurotransmitters that stimulate AMPAR activity (such as glutamate) [R]. This is because this gene also helps control a process called receptor trafficking, which determines whether receptors are on the outer surface of a neuron (where they can be activated by neurotransmitters), or whether they are withdrawn into the inside of the neuron (where they are inactive) [R, R, R, R].

In other words, KIBRA affects the number of AMPA receptors you have, as well as how sensitive they are – and this two-pronged effect is most likely why variations in this gene can have such a profound effect on many different aspects of cognitive function [R].

For example, the variations that people carry in their KIBRA gene have been associated with:

• Overall cognitive performance [R]
• Cognitive flexibility [R]
• Learning and memory [R, R, R, R]
• Working memory [R]

AMPA receptors are critical for synaptic plasticity. The KIBRA gene affects cognitive ability by controlling the number of AMPA receptors you have, as well as how sensitive they are.

Many studies have backed up the important role that KIBRA plays in cognitive performance.

For example, animals that have their KIBRA gene activity reduced (e.g. by “knocking out” the KIBRA gene) display significant deficits in learning and memory, presumably as a result of the loss of synaptic plasticity [R].

Similarly, in humans, depressed patients with cognitive symptoms have significantly lower overall KIBRA gene levels compared to healthy controls [R, R], suggesting that low KIBRA levels are at least partly for these cognitive impairments.

Carriers of beneficial KIBRA alleles are also at reduced risk of developing Alzheimer’s disease [R, R, R, R], and are more resistant to the effects of cognitive aging [R, R, R] – two disorders that famously involve deficits in learning and memory.

All together, this pattern of results suggest that KIBRA causes cognitive impairments when its levels are lower, and that the beneficial variants of this gene most likely enhance cognitive performance by increasing the overall levels of this gene.

Low KIBRA levels reduce cognitive performance, whereas relatively higher KIBRA levels are probably responsible for the enhanced cognitive abilities seen in people with beneficial alleles for this gene.

Below you can see your genotype for one of the most important and well-studied KIBRA SNPs, rs17070145:

The two possible alleles for this SNP are ‘T’ and ‘C’. When it comes to cognitive function, the ‘T’ allele is the better one to have.

For example, one of the first studies in 351 healthy young adults found that people with the ‘T’ allele were 24% better at learning a list of unrelated words, and were ~20% better at being able to remember these words a day later [R]!

A more recent study in 140 healthy older adults further confirmed that the ‘T’ allele was associated with significantly better performance on a learning and memory task. This study also recorded brain activity during the learning and memory task, and found that those with the beneficial ‘T’ allele also had larger hippocampal volumes, as well as better functional connectivity between the hippocampus and other important brain areas, such as the prefrontal cortex [R].

Many other studies have also found similar benefits of the ‘T’ allele on memory performance [R, R, R] and overall brain volume [R, R, R], making this one of the more robust SNPs for cognitive function we currently know about.

But the advantages don’t just stop there: ‘T’ carriers also seem to be more protected against the cognitive effects of normal aging [R], and may be protected against Alzheimer’s disease [R, R]!

By contrast, people with the ‘C’ allele show:

• Worse memory performance [R]
• Smaller brains (lower grey matter volume) [R]
• Greater risk of Alzheimer’s disease [R]
• Faster and more severe cognitive decline during aging [R]

The ‘T’ allele for rs17070145 is associated with enhanced learning and memory, whereas the ‘C’ allele reduces cognitive performance, and may even increase your susceptibility to cognitive aging and Alzheimer’s disease.