The Science of Memory

Neuroanatomy

The Brain

The Neuron. The neuron is composed of the cell body, which contains the nucleus, an axon that transmits information, and dendrites that receive information.

Figure 1 The Neuron. The neuron is composed of the cell body, which contains the nucleus, an axon that transmits information, and dendrites that receive information.

The brain consists of two primary cell types:  the neurons and the glial cells.  The glial cells are support cells that compose the “connective tissue” of the brain and include astrocytes, oligodendrocytes, and microglial cells.  Glial cells provide appropriate chemical environments for neurons, facilitate neuronal impulse (ie action potential) transmission, and act as scavengers within the brain and central nervous system.  Glial cells maintain the capacity for cell division, unlike most mature neurons, and are the origin for most primary brain tumors in adults.  Neurons are electrically-excitable cells that are responsible for receiving and transmitting information within the brain, and throughout the central and peripheral nervous systems.  Neurons have a very high metabolic rate and are composed of three parts:  the cell body (or soma), the axon, and dendrites (figure 1).  The cell body of the neuron contains the nucleus and hence the genes that determine the neuron’s structure and function.  The dendrites are multiple branches off of the cell body that receive and integrate information (chemically and electrically) from other neurons.  A single neuron can receive input from over 100,000 individual neurons via its dendritic tree.

Figure 2 Synapse. The axon from a single neuron is sending chemical information via neurotransmitters that bind to specific receptors located along a dendrite of the receiving neuron. This is the synaptic cleft.

Figure 2 Synapse. The axon from a single neuron is sending chemical information via neurotransmitters that bind to specific receptors located along a dendrite of the receiving neuron. This is the synaptic cleft.

Neurons convey information via a structure called the “axon.”  The axon is typically a longer cell structure that is responsible for transmitting information to other neurons. The area in which neurons interact with dendrites and axons of other neurons is called the “synaptic cleft” or “synapse” (figure 2).  The synapse is a microscopic structure that sends a chemical or electrical signal from one neuron to another neuron.  Often an action potential will travel down the neuron’s axon and result in the release of a specific neurotransmitter at the synapse.  This neurotransmitter will bind to specific receptors on the receiving (post-synaptic) neuron that will result in additional action potentials or other specific stimuli within the post-synaptic neuron.  There are several different neurotransmitters within the brain, and even within memory-specific neuronal circuits.  Since mature neurons are generally not capable of cell division, a person is born with all of the neurons that person will ever have within the brain.  The synapse is so important that neurons which are unable to make a specific synaptic connection to other neurons will not survive.

 

Memory and Learning 

Memory is one of the most important and most complex processes of the brain.  Memory formation, storage, and retrieval is central to the human essence.  Memory is critical to the function of human beings, and contributes extensively to our collective personalities by influencing our behaviors and interactions.  Short-term memory refers to information that is newly-acquired (or learned) and is present only transiently (ie minutes to hours) unless it is reinforced.  Long-term memory refers to the conversion of newly-acquired information into retained information that is present for extended periods of time, potentially one’s entire lifespan.

Figure 3 Memory Circuit of the Limbic System. This circuit consists of neurons within the hippocampus in the temporal lobe that project via the fornix to the thalamus, cingulate gyrus, entorhinal cortex of the temporal lobe, and then back to the hippocampus via the perforant path.

Figure 3 Memory Circuit of the Limbic System. This circuit consists of neurons within the hippocampus in the temporal lobe that project via the fornix to the thalamus, cingulate gyrus, entorhinal cortex of the temporal lobe, and then back to the hippocampus via the perforant path.

Learning and memory are complex physiological processes that involve many different neurons in many different areas of the brain.  The hippocampus is part of the medial temporal lobe and it is important in the formation of short-term memories.  Information travels from the hippocampus via the fornix to several different regions of the brain, including the septal nuclei, mammillary bodies, thalamus, and frontal lobes.  The thalamus is an important “relay center” within the brain that interconnects many different regions of the brain, including the cerebral cortex, the brainstem, and even the spinal cord.  This memory circuit continues with neuronal projections from the thalamus to the cingulate gyrus, and then to the entorhinal cortex of the temporal lobe.  The entorhinal cortex then projects back to the hippocampus (via the perforant path), thus completing one of the major memory circuits (figure 3).  Lesions of the hippocampus can result in significant impairment in the formation of short-term memories.  The entorhinal cortex (and other regions of the temporal lobe) also project to an important area of the basal forebrain called the nucleus basalis of Meynert.  This nucleus has widespread projections to the cerebral cortex and is important in diffuse cortical activation.  The degeneration of the nucleus basalis of Meynert  is one of the most prominent features of Alzheimer’s dementia.

 

Neurobiology

Neurotransmitters are often released at the synaptic cleft to allow transmission of information from one neuron (the sending, or “pre-synaptic” neuron) to another (the receiving, or “post-synaptic” neuron).  Neurotransmitters mediate chemical synaptic transmission (as opposed to electrical synaptic transmission).  Several neurotransmitters are critical to the development and retention of memories and are active in the memory pathways that were discussed previously.  Glutamate is utilized as the primary neurotransmitter in several memory circuits involving the hippocampus.  Acetylcholine is the primary neurotransmitter of the nucleus basalis of Meynert, and is important in diffuse cortical activation.  Other neurotransmitters include serotonin, norepenephrine, dopamine, histamine, and gamma-aminobutyric acid (GABA).  After a neurotransmitter is released by the pre-synaptic neuron, it diffuses across the synaptic cleft and binds to a receptor on the post-synaptic neuron.  This can induce an action potential in the post-synaptic neuron, thus increasing its firing rate.  However, a single action potential is a transient event and shortly thereafter the post-synaptic neuron typically returns to its baseline firing rate.  Thus, the induction of a single action potential by a neurotransmitter would not account for the development of memory, particularly long term memory, since it is a transient event.  There are some special neurons within the hippocampus; however, that exhibit persistent firing after a brief stimulation.  These neurons utilize a special calcium-activated channel (CAN) that opens in response to acetylcholine released by the pre-synaptic neuron.  This system can facilitate the development of short term memory, but typically dissipates after several seconds or a few minutes.  Thus, acetylcholine is critical in the development of short-term memory.

Long-term memory formation involves a more complex phenomenon called “long-term potentiation.”  With long-term potentiation,  a neurotransmitter receptor can be stimulated to an extent that results in a permanent increase in the firing rate of the post-synaptic neuron.  One receptor in particular (the NMDA receptor) is often involved in this process.  The NMDA receptor binds the neurotransmitter glutamate.  With a solitary action potential, the stimulus is not enough to open the NMDA receptor channel.  However, if multiple signals arrive at the post-synaptic neuron simultaneously, the NMDA receptor channel will open, resulting in an increased firing rate.  NMDA receptors can be located in various patterns along a neuron’s dendritic tree.  With selective opening of NMDA receptors on the post-synaptic neuron by a pattern of simultaneous stimuli arriving from multiple different pre-synaptic neurons, the neuron can permanently adjust its firing rate.  When this pattern of stimulation is repeated over time, it can result in permanent strengthening of the synaptic connections between this specific “circuit” of neurons.  This subsequently stimulates genetic changes in the neuron cell body by activating specific genes (ie CREB-1) that can lead to the production of specific proteins that further reinforce the synaptic connections.  In this manner, the neuronal circuit is capable of learning and the development of long-term memory.  Therefore, the old axiom “repetition builds strength” is certainly true with the development of memory.  Long-term memory is a diffuse process that occurs throughout the brain (primarily the cerebral cortex).  This is fortunate because a small focal brain injury (or stroke) does not typically impact long-term memory (although it can impede the development of short-term memory if the injury involves the hippocampus).  The NMDA receptor is one of the most important mechanisms in the development of long-term memory within the human brain, and it is the neurotransmitter glutamate that is central to this process.

 

Oxidative Stress 

Neurons have very high metabolic rates, which necessitates a consistent energy source (primarily glucose) and high levels of oxygen.  Metabolic processes can result in harmful by-products called “free radicals.”  Free radicals are incomplete molecules that have one missing electron and are normal by-products of cellular metabolism.  Since neurons have very high metabolic rates, they produce fairly large numbers of free radicals.  Free radicals interact with normal proteins in the cell in order to obtain the missing electron.  This sets off a chain reaction, called “oxidation”, in which molecules within the target protein interact with other molecules to obtain missing electrons.  This can have negative effects by inactivating important proteins and other structures within the cell that can lead to premature aging and even cell death.  The importance of oxidative stress is evident in two severe pathological conditions of the human brain and central nervous system:  Amyotrophic Lateral Sclerosis (ALS, or Lou Gehrig’s disease) and Alzheimer’s Dementia.  ALS can result from genetic defects in an enzyme called “superoxide dismutase” (SOD).  The role of SOD in neurons is to prevent oxidative stress by inactivating oxygen free radicals.  Defects in SOD result in ALS, which causes the cell death of motor neurons in the brain and spinal cord.  Alzheimer’s dementia is characterized by the development of specific protein plaques within neurons called “amyloid beta-peptide.”  This amyloid plaque increases the production of free radicals within the neuron, which leads to premature aging and cell death.

 

Blood-Brain Barrier

The blood-brain barrier (BBB) is a unique vascular adaptation that is present only in the brain.  Endothelial cells are specialized cells that line the inside of blood vessels.  Endothelial cells that line blood vessels within the brain are unique because they are “sandwiched” tightly against each other.  The outer membrane of each endothelial cell literally joins together with the membrane of the adjacent cell, forming “tight junctions” that are almost impermeable.  It is these tight junctions that compose the BBB, and this developed to prevent toxins that are present within the blood stream from entering the brain.  These tight junctions are surrounded by specialized foot processes of astrocytes, which induce the formation of the BBB.  Only a few substances readily cross the BBB and enter the brain, including glucose, some electrolytes, some amino acids, and lipid-soluble substances.  This renders drug delivery to the brain very difficult, as most drugs are transported out of the brain, rapidly degraded upon entry into the brain, or prevented from entering the brain entirely.

 

Scientific Basis for Daily Brain Booster

Daily Brain Booster contains precursors of the two most important neurotransmitters (Acetylcholine and Glutamate) involved with memory formation.  Daily Brain Booster also includes stimulants and vitamins to improve overall energy levels.  Daily Brain Booster contains specific antioxidants to reduce oxidative stress in neurons to improve long term neuronal metabolism.  All of these ingredients are readily absorbed by the gastrointestinal tract and readily cross the blood-brain barrier.  The active ingredients in Daily Brain Booster have been proven clinically to improve memory and cognitive function (see “References” section).