Best Nootropics for Memory

Memory

Your memory is the center of your knowledge, beliefs, understanding, and self-image, everything. It’s very important to be able to process, store and eventually retrieve information. If you have the ability to do so, you will have huge benefits. And there are several effective nootropic supplements which can help boost your memory and also can help enhance the ability of your brain to process and store the information received from your senses. Storage and retrieval to and from short-term and long-term memory become quicker and it requires less effort. Whatever your profession, better memory can make everything easier and better for you. In this article, we will discuss about how memory works in your brain and provide you with suggestions on nootropics that you can add to your stack for each step of the memory process.

How Memories are Formed

The process how the memories are formed in your brain is very interesting. A new memory usually involves interactions between thousands of neurons. When this new encoding doesn’t get used, soon it fades. But if you continue to reactivate the information that you have stored by re-reading a sentence, the connections become reinforced. Some parts of your brain are involved in this process of memory encoding and storage, especially your cerebral cortex and hippocampus.

Memory and different parts of the brain

Here we will discuss the formation of memories in the brain parts and the recommended nootropics for the specific parts of the brain.

Hippocampus

Recently researchers at the University of Bonn recognized the mechanism of action behind memory switching from recall to memorization mode. Every new sensation you experience including taste, sound, and sight initially enters your hippocampus. It also retrieves stored information from deep within your memory. In your hippocampus, acetylcholine (ACh) stimulates astrocyte cells which then are induced to release the neurotransmitter glutamate. Then the released glutamate activates inhibitory neurons that inhibit pathways mediating the retrieval of memories. This process is one of the reasons acetylcholine (ACh) helps enhance memory and learning.[30]
As a nootropic, you can use choline supplement precursors to produce ACh.[31] You can also use Choline Citrate,[32] CDP-Choline,[33] Centrophenoxine,[34] and Alpha GPC.[35]

Glial Cells

A report published in the journal Neuron about memory prioritization is particularly significant as astrocytes are glial cells. Nearly 90 percent of the brain is composed of glial cells, not neurons.(This idea might claim that we only use 10% of our brain).[1] Types of glial cells include astrocytes, ependymal cells, microglia, Schwann cells, and oligodendrocytes. Studies show that glial cells in your hippocampus and cerebellum participate in synaptic transmission, regulate the clearance of neurotransmitters from the synaptic cleft (preventing glutamate toxicity), and release gliotransmitters like ATP that modulate synaptic function.[2] The star-shaped glial cells such as astrocytes link neurons to their blood supply in your brain and help form the blood-brain barrier. Again, astrocytes regulate the expansion and contraction of blood vessels. Clearly, astrocytes are important to cerebral circulation (brain blood flow).[3] They also help provide nutrients to neurons in your brain keeping a role in the repair and scarring process in your brain and spinal cord following traumatic injury.[4]
The most used nootropics to increase blood flow to, and throughout your brain are Vinpocetine,[36] Bacopa Monnieri [37] and Gingko Biloba.[38]
 
Again, oligodendrocytes are the glial cells that help produce the myelin sheath (looking like wrapping a wire in electrical tape) coating axons in your brain. It provides protection, and allows electrical signals (action potential) to be more efficient [5] and is very important in memory encoding and retrieval. The regions where myelination occurs are responsible for higher-level reasoning, planning and judgement, skills that come with experience. As teenagers usually have less fore-brain myelin, they do not have adult decision-making abilities. A study shows that practicing over time, musicians’ white matter increased because their axons were more heavily myelinated or tightly packed. That means while learning a complex skill, there are noticeable changes in white matter in your brain.[6]
You can take Sulbutiamine,[39] Vitamin B1 (thiamine),[40] SAM-e,[41] Vitamin B12 (Methylcobalamin),[42] and Vitamin B9 (Folate)[43] to produce critical myelin sheath for your brain’s axons.

Dendrites

Unfortunately, whatever we do in our day to day life, we can’t remember everything, but some things only. Whenever you do anything, it requires the activity of millions of neurons in your brain. Though millions of neurons are activated during a single commute, all information isn’t stored in your brain. The scientists in Northwestern University found that dendrites are not always activated when the cell body is activated in the neuron. Signals produced in the dendrites are used to store information. And signals in the neuron cell body are used to compute and transmit, but not store information.[7]
As dendrites are not storing all information, if you observe, you will notice that many patients suffering from Alzheimer’s Disease may be unable to find their way home. You can say that dendrites are like branches projecting out of neurons that act like an antenna and receive electrical signals sent by the synapses of neighboring neuron axons. You can have as many as 15,000 dendrites projecting from a single neuron.[8] When you experience incoming stimuli from your senses, neuron activity increases and dendritic spines change size, shape and conduction leading to long-term potentiation (LTP) which play a fundamental role in learning and memory.
The suggested nootropics to boost dendrite health include Ashwagandha,[44] Artichoke Extract,[45] DHA,[46] Gotu Kola,[47] and Turmeric.[48]

Axons

In your brain, every single neuron can have thousands of dendrites, but only one axon. The axon is used to transmit an action potential (electrochemical signal) down the length of the axon with the intent of finding neighboring neuron’s dendrites to communicate with. Again, the neurotrophic factors, such as nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF) and neurotrophin 3 (NT3) are involved in axon development. When the action potential reaches a presynaptic terminal (tip of the axon), it activates the synaptic transmission process. The first step is opening calcium ion channels in the axon, allowing calcium ions to flow across the axon, which causes vesicles (tiny containers enclosed by a lipid membrane) filled with a neurotransmitter to fuse with the axon’s membrane and empty their contents into the extracellular (outside) space. The neurotransmitter diffuses across the synapse to receptors located on dendrites of the target cell and binds to those receptors and activates them. Depending on the type of receptors activated, the effect on the target cell can be to excite the target cell, inhibit it, or alter its metabolism and this entire process takes less than 1,000th of a second.[9] Later the presynaptic axon terminal moves a new set of vesicles into position – ready for release when the next action potential arrives. This is how memories are formed and affects alertness, concentration, cognition and mood.
The recommended nootropics to maintain axon health in your brain are Ashwagandha,[49] Gotu kola,[50] Vitamin B1 (Thiamine),[51] Vitamin B6 (Pyridoxine),[52] and Vitamin B12 (Methylcobalamin).[53]

Neuroplasticity

The fundamental mechanisms involved in neuroplasticity include neurogenesis (growth of new neurons), dendrites and axons, cell death (apoptosis), and synaptic plasticity. Recurring stimulation of synapses can result in long-term potentiation or long-term depression of neurotransmission. These changes are associated with physical changes in dendritic spines and neuronal circuits that influence your behavior, memory and mood. Neuroplasticity is much more active during childhood but it remains with us into adulthood.[10] Studies have been done to measure and study neuroplasticity in human brains for decades[11] and researchers have found out how and why many nootropics work to boost memory. Donald Hebb, in his book “Organization of Behavior: A Neuropsychological Theory”, said about neuroplasticity [12] where he expressed his theory that your brain adapts to its environment based on experience and development; thinking and learning change your brain’s physical structure and functional organization. Hebb also coined the term so often quoted in nootropic circles, “neurons that fire together, wire together”. Almost all the nootropics influence neuroplasticity. However, you can boost neuroplasticity in other ways as well.

Meditation and Neuroplasticity

Meditation has a great impact on our brain formation. A number of studies how the regular practice of meditation affected the normal age-related cognitive decline of gray matter in the brain. A study found that Zen meditators did not experience any significant reduction in gray matter while the non-meditators showed the expected loss of gray matter as well as loss of attention performance.[13]
To see the effects of meditation on the brain, neuroscientist Richard Davidson of the University of Wisconsin led experiments with the Dalai Lama. It showed that mediation practice results in different brain activity levels associated with attention, anxiety, depression, fear, anger, and even the ability of the body to heal itself. The study concluded these functional changes resulting from meditation may be caused by changes in the physical structure of the brain.[14]

Fitness – Exercise and Neuroplasticity

It is proven that fitness and exercise play an important role on the formation of the brain. Aerobic exercise boosts adult neurogenesis by increasing the production of Brain-Derived Neurotrophic Factor (BDNF), insulin-like growth factor 1 (IFG-1), and vascular endothelial growth factor (VEGF).[15] Neurogenesis in the hippocampus from exercise is associated with better spatial memory.[16] And consistent aerobic exercise over several months significantly boosts executive function and increased gray matter volume in the prefrontal cortex and hippocampus.[17]

ADHD Stimulants and Neuroplasticity

Several studies on ADHD patients using MRI’s suggest that long-term treatment of ADHD with stimulants like amphetamine or methylphenidate (Ritalin) decreases abnormalities in brain structure and function and improves neuroplasticity in several parts of the brain.[18] However, studies with ADHD stimulants with ‘normal’ adult brains (people not being treated for ADHD) showed mixed results; some studies showed ADHD stimulants reduced neuroplasticity in the healthy adult brain.[19]

The Molecular Biology of Memory

Since this article is about nootropics, we will just dicuss how nootropics influence brain function and what you can do to improve your memory. You’ve already known that thousands of neurons, dendrites, axons, neurotransmitters, action potentials, neuroplasticity and growth factors all contribute to the formation of memories; and some of the nootropic supplements that can assist each of these. Still, for your better understanding how memories are formed and recalled, we will discuss about the molecular biology of memory.
There are basic steps in the molecular biology of short-term memory as well as its conversion to long-term memory for both implicit (procedural memory responsible for motor skills, and knowing how to do things such as talking, walking and driving your car) and explicit (declarative memory including episodic memory such as your store of people, places, and objects, and semantic memory such as your store of facts and events) memory.

Short-Term Memory

Incoming stimulus from your senses to your brain stimulates the release of serotonin (5-HT). 5-HT binds 2 types of receptors on the neuron; one is coupled to the DAG (diglyceride)/PKC (protein kinase C) system, and the other is coupled to the cyclic AMP (Cyclic adenosine monophosphate)/PKA (protein kinase A) system. Both are signaling pathways. Again, these protein kinases exert 2 types of actions. First, they regulate the properties of membrane channels in the presynaptic neuron which regulates the amount of calcium that enters the synaptic terminal during an action potential and causes a boost in the release of the neurotransmitter leading to an increase in the excitability of the post-synaptic neuron. Second, kinases regulate the cellular processes involved in neurotransmitter release including the pool of available synaptic vesicles available for release in response to the incoming Ca2+ (calcium ions) with each action potential. Finally, serotonin (5-HT) leads to changes in the properties of the post-synaptic neuron including an increase in the number of glutamate receptors.
Again, learning involves the engagement of second messenger systems where protein kinase C (PKC) and protein kinase A (PKA) come in and cyclic AMP (cAMP) is one of the critical second messengers involved in memory. PKA will only be activated for a short time after a brief stimulus because cyclic AMP will be degraded and PKA levels will decrease. Protein phosphatase will remove the phosphate groups on the proteins that are storing these short memories.[20] If you are able to form short-term memories, you’ll also be able to form long-term memories.
You can increase short-term memory with the nootropics Huperzine-A,[54] Kava,[55] Rhodiola Rosea,[56] Phosphatidylserine (PS),[57] DMAE and Nicotine.[58]

Long-Term Memory

Now let’s know about long-term memory. Actually, a significant difference between the 2 types of memories is – long-term memory requires new protein synthesis and gene regulation and expression, while short-term memories do not. Long-term memories typically involve physical modifications in your brain which is otherwise known as neuroplasticity. Long-term memory relies on long-term potentiation which is a strengthening of synapses between neurons resulting from repeated activity in the brain. Long-term potentiation comes in 2 forms: early long-term potentiation (E-LTP) which lasts 1 – 3 hours, and late long-term potentiation (L-LTP) which last 6 – 10 hours.[21]
 

The Receptors

The NMDA glutamate receptors are involved in long-term potentiation (LTP) with CA3-CA1 synapses in your hippocampus. Post-synaptic spines of CA1 neurons have 2 types of glutamate receptors; NMDA-type glutamate receptors and AMPA-type glutamate receptors. Both types of receptors respond to sodium ions (Na+) and potassium ions (K+). But the NMDA receptor is also responsive to calcium ions (Ca2+), and can be blocked by magnesium ions (Mg2+). When the NMDA receptor is activated by an electrical signal from a neighboring neuron, calcium ions enter that neuron and stimulate Ca2+/calmodulin-dependent protein kinase II (CaMKII). CaMKII regulates neurotransmitter synthesis and release, modulates ion channel activity, gene expression and is critical to learning and memory.[22] It, i.e., CaMKII also makes AMPA receptors more active and recruits more AMPA receptors to the synaptic cleft which strengthens E-LTP and helps form short-term memories.[23]
Studies show that ampakine nootropics like Aniracetam, Coluracetam, Noopept, Oxiracetam, Piracetam, and Resveratrol can increase synapse response and enhance long-term potentiation.[24]
Again, the activation of NMDA receptors results in an influx of calcium at the synaptic cleft. Repeated influxes of these signals activate the proteins Ras-specific guanine nucleotide-releasing factor 2 (Ras-GRF2) and Ras-specific guanine nucleotide-releasing factor 1 (Ras-GRF1) which stimulates Ras (reticular activating system) and extracellular-signal-regulated kinases (ERK).[25] ERK integrates many signals in your brain. If the ERK is blocked, long-term memory is inhibited.[26]
The nootropic Turmeric can be used to activate ERK.[59]
Ras can also be activated by Brain-Derived Neurotrophic Factor (BDNF).[27] And in long-term potentiation, the Ras/ERK pathway combines with the cAMP/PKA pathway to activate cAMP response element-binding protein (CREB), which causes gene transcription activity in the neuron’s nucleus and creates more permanent strengthening of neuronal networks.[28]
You can use the nootropics PQQ,[60] and Pterostilbene [61] to help boost CREB.
cAMP is a second messenger involved in short-term memory, which is also involved in producing long-term memory. cAMP effects the membrane channels like in short-term memory. But in long-term memory, cAMP with PKA also phosphorylates (introduces a phosphate group) transcription factors like cAMP responsive element binding protein (CREB). cAMP is degraded by the PDE4 enzyme. If you inhibit PDE4, you increase the duration of CREB’s activity by prolonging cAMPs activation of CREB via PKA.[29]
You can inhibit PDE4 with Resveratrol,[62] Oat Straw [63] and Artichoke Extract.[64] And you can increase cAMP with Forskolin [65] and Vinpocetine.[66] Actually, Artichoke Extract and Forskolin are key ingredients in the CILTEP stack.
And in conclusion, Nefiracetam has been shown to increase the amount of time calcium channels in neurons remain open.[67] Tied to protein kinase A (PKA) and the Gi alpha subunit (Gi/o protein), signaling is enhanced in the neuroreceptor independent of the synapse. This calcium channel pathway is critical for long-term potentiation (LTP) and the formation of long-term memories. Nefiracetam also potentiates protein kinase C alpha (PKCα) which is involved in long-term potentiation (LTP). PKCα is dependent on glutamate signaling. And Nefiracetam activates Ca2+/calmodulin-dependent protein kinase II (CaMKII) which is critical in memory formation but dependent on glutamate signaling.

Final Considerations

Memory touches every aspect of your life whether it is to remembering your anniversary to finding your home. Nootropic stack can help you improve your memory and cope with real life situation. But, you don’t need to attempt to use every single nootropic mentioned in this post. Take care in assembling your nootropic stack to include at most, one from each section. Remember, nootropic supplements work in synergy.

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