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How to Improve Synaptic Plasticity For Brain Function

Written by Nattha Wannissorn, PhD | Last updated:

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It was once thought that if we have any damage in our brain later in life or if something prevented healthy brain development, we would be fated to live with it. However, in 1966, the discovery of synaptic plasticity overturned that belief. This gave new hopes to people with brain damage, neurological diseases, or learning disabilities [1].

In fact, the brain is a lot more flexible and resilient than we previously thought. Neurons can regrow and new neuronal connections can be made. This allows us to learn new skills and repair the brain that may be damaged from head traumas, stress, toxins, or even a lifetime of poor diet and lifestyle choices – at any time in life.

Synaptic plasticity is our brain’s key to the formation of new memories and neural networks; particularly, within the hippocampus. It is possible to support this process naturally with diet and lifestyle.

Read on to take a closer look at some foods and active ingredients that are tested, and proven, to increase synaptic plasticity.

What is Synaptic Plasticity?

Our brain contains approximately 100 billion neurons. These neurons communicate with one another by synapsing.

An electrical signal generated by a neuron sends chemicals (neurotransmitters) from one neuron to another. Thus, the small space in between the two communicating neurons is the synapse [R].

What is a Synapse?

In this 1:52 min video, 2-Minute Neuroscience explains the process of a synapse between two neurons.

[youtube https://www.youtube.com/watch?v=WhowH0kb7n0]

Synaptic plasticity refers to our brain’s ability to strengthen existing and form new connections between neurons. This process is accomplished by forming new synapses and rewiring neural circuits, in response to new stimuli [2].

Synaptic plasticity is a subset of the brain or neuronal plasticity. Brain plasticity includes the generation of new neurons (neurogenesis) and synapses as well as strengthening existing synapses (synaptic plasticity).

This 4:30 min video describes synaptic plasticity and its importance in learning new motor (movement) skills.

[youtube https://www.youtube.com/watch?v=8Vo-rcVMgbI?start=24]

Glutamatergic System and Synaptic plasticity

Glutamate is the most important neurotransmitter for synaptic plasticity [3].

Glutamate receptors that are involved include AMPA (hydroxy-3-methyl-4-isoxazole propionic acid) and NMDA (N-methyl d-aspartate) receptors.

Therefore, glutamate is important in memory and long-term potentiation.

Choline and cholinergic nerve signal transmission may also be important [4].

Why is Synaptic Plasticity Important?

1) Synaptic Plasticity is Important for Learning and Memory

Intrinsic brain plasticity (flexibility), or the ability of the brain to rewire, is an important and evolutionarily conserved neural correlate of learning [5].

Intrinsic plasticity is an important predictor of learning-induced behavioral plasticity [6].

Synaptic plasticity allows for long-term potentiation – or increasing the strength of our synapses with more use, which allows us to memorize or become fluent at the things we learn. Therefore, synaptic plasticity is essential for learning and memory [7].

The Role of Synaptic Plasticity in The Hippocampus (Memory Center) 

Located in the medial temporal lobe, the hippocampus plays a key role in forming new associations and consolidating stimuli into new memories [8].

Specialized cells in the hippocampus can undergo mitosis (cell division) to generate new brain cells [9]. Synaptic plasticity is important for these cells to integrate with other hippocampal cells.

2) Synaptic Plasticity Helps Recover from Brain and Nervous System Injuries

Through neuroplasticity, the central nervous system can remarkably recover from brain injuries. In addition, the brain can adapt through secondary compensatory mechanisms when there is some brain tissue damage [10].

Preliminary work suggests that long-lasting morphological changes occur in the hippocampus after traumatic brain injury, including the growth of cell soma and recruitment of neurons to the hippocampus [11, 12].

Spinal injuries that damage the sensorimotor pathways are known to cause synaptic changes in neuronal circuitry, within the spinal cord and at higher levels, over the postinjury weeks and months [13].

Conditions that Impair Synaptic Plasticity

1) Age-Related Cognitive Dysfunction

In the aging brain, cognitive function gradually declines and causes a progressive reduction in the structural and functional plasticity of the hippocampus [14].

2) Alzheimer’s and Parkinson’s Disease

In Alzheimer’s and Parkinson’s disease patients, the amyloid plaque that causes the diseases can impair synapse structure and function [15, 16].


Synaptic plasticity in the amygdala may be involved in PTSD and an important target for its treatment [17].

4) Schizophrenia, Anxiety, and Depression

Synaptic plasticity may also have a role in the development of anxiety and schizophrenia [18].

Schizophrenia may be a disease of short-term synaptic plasticity alterations [19].

In schizophrenia patients, AMPA receptors are inhibited. This changes long-term potentiation or the ability to form normal memory [20].

Interestingly, chronic administration of typical antidepressants that block the reuptake and breakdown of monoamines, increase synaptic plasticity [2122].

5) Autism

Autism has been found to alter signaling pathways that are active while synaptic plasticity is taking place [23, 24, 25].

6) Sleep Deprivation

5–6 h of sleep deprivation impairs long-term potentiation maintenance, hindering synaptic plasticity [26].

Stressful events early in life induce long-term sleep disturbances and alter long-term synaptic plasticity [26].

7) Seizures

Rats with seizures have alterations in the long-term potentiation in synapses of the somatosensory cortex [27].

8) Other Diseases that Can Impair Synaptic Plasticity

  • Borna disease virus infection impairs synaptic plasticity [28].
  • Angelman syndrome impairs synaptic plasticity through cell mutation [20, 29].
  • Noonan syndrome [20].
  • Tuberous sclerosis [20].

Molecules/Hormones In Our Bodies That Aid Synaptic Plasticity

1) Brain-Derived Neurotrophic Factor (BDNF)

Brain‐derived neurotrophic factor (BDNF) supports neuronal survival and growth while plays a specific role in hippocampal synaptic plasticity [30].

2) Healthy Glutamate Levels and Metabolism

Glutamate transport is associated with the formation of synapses, synaptic plasticity, learning, and memory [31, 32].

3) Nerve Growth Factor (NGF)

Nerve growth factor (NGF) promotes long-term memory formation [33, 34].

4) Testosterone

In male rats, testosterone relates to memory performance and synaptic plasticity [35, 36].

5) Estradiol

Estradiol (an estrogen signaling molecule) affects hippocampal-dependent spatial memory and structural/electrical synaptic plasticity in female mice and rats [37, 38].

6) Leptin

Administration of leptin into the brain facilitates hippocampal long-term potentiation and improves memory performance [39, 40, 41].

7) Secretin

Secretin has been linked to synaptic plasticity and social behavior, in the mouse model [42].

8) Erythropoietin (EPO)

In a rat model of Alzheimer’s, erythropoietin improves synaptic plasticity and reduce glutamate levels (typically high in Alzheimer’s) [43].

9) Pregnenolone Sulfate

Pregnenolone sulfate is a steroid hormone that has beneficial effects on the brain. By enhancing NMDA and other neurotransmitter receptors, pregnenolone seems to help with synaptic plasticity for learning and memory [44].

Natural Ways to Increase Synaptic Plasticity

Certain foods can increase the number of synaptic connections [45].

1) Polyphenols Can Activate Synaptic Plasticity

Fruits, vegetables, cereals, and beverages contain natural polyphenols. Grapes, apples, pears, cherries, and berries contain up to 200-300 mg of polyphenols in every 100 grams serving [46].

Phenolic acids, flavonoids, phenolic amides, resveratrol, lignans, curcumin, rosmarinic acid/caffeic acid, ellagic/gallic acid, and tannins are types of polyphenols [47].

Polyphenols possess unique properties that can battle oxidative stress and stimulate the activation of molecules that aid in synaptic plasticity [48].

2) Red Wine and Resveratrol Can Enhance Learning Ability

Resveratrol is a polyphenol abundant in grapes, red wine, berry fruits, and some nuts [47].

In rat neurons, resveratrol can rapidly increase AMPAR protein levels, AMPAR synaptic accumulation, and the strength of excitatory synaptic transmission [49].

AMPARs are glutamate-associated receptors that are important for fast excitatory transmission and synaptic plasticity [49].

Resveratrol significantly enhanced the learning ability of diabetic rats, because it has antioxidant and anti-inflammatory activities as well as the ability to facilitate hippocampal structural synaptic plasticity [50].

Six weeks of resveratrol supplementation in diabetic mice resulted in normalization of the expression of genes implicated in hippocampal neurogenesis and synaptic plasticity [51].

Recent studies showed that resveratrol is a known activator of the SIRT1 gene, which has antiproliferative and anti-inflammatory activities [52, 53].

Mice without the brain-specific SIRT1 gene have decreased synaptic plasticity [54].

3) Green Tea Can Improve Memory

The active compounds in green tea are predominantly polyphenols and caffeine. In mice with impaired long-term memory due to abnormal levels of DYRK1A gene (involved in learning), green tea polyphenol treatment lessened the cognitive deficits [55].

Green tea polyphenols (EGCG) increase cognitive function and mood while protects against various brain diseases [48].

In a 12-participant study (DB-RCT), green tea extract increased working memory [56].

Green tea extract increased both working and spatial memory in mice [57].

Flavonoids, a group of major constituents of green tea, inhibit cell death triggered by neurotoxic compounds and an increase in synaptic plasticity [58].

4) Berries Have Anti-Aging Properties

Recent studies have demonstrated that berries improve cognitive functions. Compounds in berries reduce inflammation and increase cell survival, neurotransmission, and neuroplasticity [59].

In cell-based studies, aging animals given a blueberry-enriched diet showed an increase in both long-term potentiation and synaptic strength to levels seen in young controls [60].

Resveratrol, a phenolic compound abundant in berries, protects neurons against amyloid beta-induced toxicity (involved in Alzheimer’s) and reduces memory degeneration in rats [61].

5) Soy Can Improve Spatial-Memory Acquisition

Soy contains plant-derived, non-steroidal compounds with estrogen-like effects (phytoestrogens) [62].

Studies suggest that estrogens are positive regulators of learning and memory function, in women [63, 64].

Female rats without ovaries (a menopausal model) supplemented with soy germ phytoestrogens performed significantly better in spatial memory acquisition and retention when compared to rats fed on a control diet [65].

6) Cocoa Improves Synaptic Plasticity

Cocoa powder and chocolate contain a large percentage of flavonoids, which can [66]:

  • Inhibit neuronal cell death induced by neurotoxins, such as oxygen radicals
  • Promote neuronal survival
  • Improve synaptic plasticity

Flavonoids in cocoa increase adult hippocampal neurogenesis in chronically stressed rats [67].

The flavonol quercetin, a major component of cocoa extracts, improved learning and memory impairment in rats that lack oxygen to the brain [68].

7) Acetyl-L-Carnitine (ALCAR) Can Help Increase Synaptic Plasticity

In aging rats, chronic administration of dietary carnitine increases choline-associated synaptic transmission and, consequently, enhances learning capacity [69].

In a clinical study (DB-RCT), carnitine improved clinical scales and benefited psychometric tests in 1,204 patients with Alzheimer’s at early disease stages [70].

Acetyl-L-carnitine increased synaptic strength and produced a lasting activity-dependent plasticity in sensory networks by increasing the strength of neuronal signals after the synapses (afterhyperpolarization amplitude) [71].

8) Fish Oil (DHA and EPA) Can Enhance Learning and Memory

DHA and EPA (omega-3 fatty acids) in fish oil enhance synaptic plasticity by [72]:

  • Increasing production of proteins in the synapses
  • Facilitating the formation of protein complexes that are involved in the transport and release of neurotransmitters into the synapses (also called SNARE complexes) [73]
  • Increasing the density of dendritic spines (the postsynaptic neuron’s appendages that extend to the postsynaptic axons) in the hippocampus [74]
  • Long-term potentiation
  • Enhancing the creation of new neurons in the hippocampus

These findings suggest that DHA supplementation helps with neurodegenerative diseases and improves brain function [73].

9) Magnesium (Mg) Can Prevent Memory Decline in Alzheimer’s disease

Increasing extracellular magnesium within the physiological range enhances synaptic plasticity in neurons of the hippocampus [75].

MgT (magnesium-L-threonate)-treated rats showed an increase in the activation of NMDA transmission, presynaptic connections, and synaptic plasticity in the hippocampus along with memory enhancement [76].

In a mouse model of Alzheimer’s disease, magnesium treatment reduced amyloid-β plaque and prevented synapse loss and memory decline [77].

10) Zinc (Zn) Can Increase Synaptic Plasticity

Zinc can activate the enzyme Erk in neurons [78]. This stimulation increases synaptic plasticity [79].

Zinc is an important mineral for neurotransmitter release from glutamate neurons, suggesting that zinc may be also involved in synaptic plasticity [80].

11) Curcumin Improves Spacial Memory

Curcumin significantly improved spatial memory impairment induced by HIV-1 in rats [81].

Noteworthy, curcumin can stimulate developmental and adult hippocampal creation of neurons, which may enhance neuronal plasticity and repair [82].

Curcumin also increases DHA levels within the brain, which enhances learning and memory independently [83].

12) Berberine Can Improve Memory Impairment in Diabetes

Treatment with berberine ameliorates memory impairment and improves synaptic plasticity in streptozotocin-induced diabetic rats [84].

Berberine increases synaptic plasticity by reversing synaptic impairment induced by d-galactose [85].

In rats, berberine prevented changes in oxidative stress and, consequently, improved memory impairment [86].

13) Rehmannia Can Help in the Formation of New Neurons

Rehmannia is an active ingredient in the Liuwei Dihuang Decoction, which improves synaptic plasticity by inhibiting voltage-dependent calcium channels and increasing the function of NMDA receptors [87].

Catalpol, a component of Rehmannia, increases neuronal plasticity, stimulates the creation of new neurons, and enhances synaptic plasticity [88].

14) Bitter Melon Reduce Oxidative Stress in the Brain

In mice, bitter melon (Momordica Charantia) increased Sirt1 levels. This helps reduce oxidative stress and improve synaptic plasticity in the brain [89].

Also, bitter melon improves inflammation of neurons due to obesity [89].

15) Saffron Protects the Neurons

Among other health benefits, saffron has neuroprotective effects [90].

Streptozotocin is a neurotoxin that reduces the number of neurons in the hippocampus. Crocin, the major yellow pigment in saffron, helps mitigate memory impairments caused by streptozotocin.

Crocin may be the active component in saffron that improves learning and memory [91].

16) Uridine Can Enhance Cognitive Functions

The rates at which brain neurons form new dendritic spines and synapses depend upon brain levels of three compounds: uridine, DHA, and choline. Therefore, without uridine, synaptic plasticity would certainly not increase [92].

Uridine, together with DHA and choline, enhanced cognitive functions and neurotransmitter release in experimental animals and significantly improved memory in 220 patients with Alzheimer’s disease [92].

Results from various cell-based studies indicate that uridine can promote axon growth and bulk transport mechanisms [93, 94, 95], which are important processes in synaptic plasticity.

17) Fasting Induces Autonomic Synaptic Plasticity

Fasting causes a form of autonomic synaptic plasticity that prevents low blood sugar [96].

Therefore, fasting stimulates AMPK activity required by hypothalamic AgRP neurons [97, 98].

AMPK activity in the hypothalamus is higher in fasted versus refed mice [99].

Moreover, a fasting-induced increase in ketone bodies influences neuronal excitability and neurotransmitters release [100, 101].

Finally, acute fasting increases retrograde synaptic enhancement [102].

18) Exercise Increases Synaptic Plasticity

In both humans and mice, exercise increases BDNF, which helps increase neurons in the hippocampus and increase synaptic plasticity throughout the brain [103].

In rats, long-term exercise (~2 months) seems to be necessary for the generation of new neurons and sustained increase in synaptic plasticity [104].

19) Serine Improves Synaptic Plasticity

D-serine binds to and activates NMDA receptors, which can improve synaptic plasticity [105].

In astrocytes (a type of glial cells that do cellular cleanups and maintain brain health), L-Serine (the natural form of serine) can be converted into D-Serine with the enzyme called serine racemase [105].

About the Author

Nattha Wannissorn

Nattha Wannissorn

Nattha received her Ph.D. in Molecular Genetics from the University of Toronto and her undergraduate degree in Molecular and Computational Biology from the University of Pennsylvania.
Aside from having spent 15 years in biomedical research and health sciences, Nattha is also a registered holistic nutritionist, a certified personal trainer, has a precision nutrition level 1 certification, and is a certified functional diagnostic nutrition practitioner. As a holistic practitioner with a strong science background, Nattha is an advocate of science literacy in health topics and self-experimentation.

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