Excitatory synapse

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A diagram of a typical central nervous system synapse. The spheres located in the upper neuron contain neurotransmitters that fuse with the presynaptic membrane and release neurotransmitters into the synaptic cleft. These neurotransmitters bind to receptors located on the postsynaptic membrane of the lower neuron, and, in the case of an excitatory synapse, may lead to a depolarization of the postsynaptic cell. SynapseSchematic en.svg
A diagram of a typical central nervous system synapse. The spheres located in the upper neuron contain neurotransmitters that fuse with the presynaptic membrane and release neurotransmitters into the synaptic cleft. These neurotransmitters bind to receptors located on the postsynaptic membrane of the lower neuron, and, in the case of an excitatory synapse, may lead to a depolarization of the postsynaptic cell.

An excitatory synapse is a synapse in which an action potential in a presynaptic neuron increases the probability of an action potential occurring in a postsynaptic cell. Neurons form networks through which nerve impulses travels, each neuron often making numerous connections with other cells of neurons. These electrical signals may be excitatory or inhibitory, and, if the total of excitatory influences exceeds that of the inhibitory influences, the neuron will generate a new action potential at its axon hillock, thus transmitting the information to yet another cell. [1]

Contents

This phenomenon is known as an excitatory postsynaptic potential (EPSP). It may occur via direct contact between cells (i.e., via gap junctions), as in an electrical synapse, but most commonly occurs via the vesicular release of neurotransmitters from the presynaptic axon terminal into the synaptic cleft, as in a chemical synapse. [2]

The excitatory neurotransmitters, the most common of which is glutamate, then migrate via diffusion to the dendritic spine of the postsynaptic neuron and bind a specific transmembrane receptor protein that triggers the depolarization of that cell. [1] Depolarization, a deviation from a neuron's resting membrane potential towards its threshold potential, increases the likelihood of an action potential and normally occurs with the influx of positively charged sodium (Na+) ions into the postsynaptic cell through ion channels activated by neurotransmitter binding.

Chemical vs electrical synapses

Animation showing the function of a chemical synapse.
There are two different kinds of synapses present within the human brain: chemical and electrical. Chemical synapses are by far the most prevalent and are the main player involved in excitatory synapses. Electrical synapses, the minority, allow direct, passive flow of electric current through special intercellular connections called gap junctions. [3] These gap junctions allow for virtually instantaneous transmission of electrical signals through direct passive flow of ions between neurons (transmission can be bidirectional). The main goal of electrical synapses is to synchronize electrical activity among populations of neurons. [3] The first electrical synapse was discovered in a crayfish nervous system. [3]
Chemical synaptic transmission is the transfer of neurotransmitters or neuropeptides from a presynaptic axon to a postsynaptic dendrite. [3] Unlike an electrical synapse, the chemical synapses are separated by a space called the synaptic cleft, typically measured between 15 and 25 nm. Transmission of an excitatory signal involves several steps outlined below.

Synaptic transmission

  1. In neurons that are involved in chemical synaptic transmission, neurotransmitters are synthesized either in the neuronal cell body, or within the presynaptic terminal, depending on the type of neurotransmitter being synthesized and the location of enzymes involved in its synthesis. These neurotransmitters are stored in synaptic vesicles that remain bound near the membrane by calcium-influenced proteins.
  2. In order to trigger the process of chemical synaptic transmission, upstream activity causes an action potential to invade the presynaptic terminal.
  3. This depolarizing current reaches the presynaptic terminal, and the membrane depolarization that it causes there initiates the opening of voltage-gated calcium channels present on the presynaptic membrane.
  4. There is high concentration of calcium in the synaptic cleft between the two participating neurons (presynaptic and postsynaptic). This difference in calcium concentration between the synaptic cleft and the inside of the presynaptic terminal establishes a strong concentration gradient that drives the calcium into the presynaptic terminal upon opening of these voltage-gated calcium channels. This influx of calcium into the presynaptic terminal is necessary for neurotransmitter release.
  5. After entering the presynaptic terminal, the calcium binds a protein called synaptotagmin, which is located on the membrane of the synaptic vesicles. This protein interacts with other proteins called SNAREs in order to induce vesicle fusion with the presynaptic membrane. As a result of this vesicle fusion, the neurotransmitters that had been packaged into the synaptic vesicle are released into the synapse, where they diffuse across the synaptic cleft.
  6. These neurotransmitters bind to a variety of receptors on the postsynaptic cell membrane. In response to neurotransmitter binding, these postsynaptic receptors can undergo conformational changes that may open a transmembrane channel subunit either directly, or indirectly via a G-Protein signaling pathway. The selective permeability of these channels allow certain ions to move along their electrochemical gradients, inducing a current across the postsynaptic membrane that determines an excitatory or inhibitory response.

[3]

Responses of the postsynaptic neuron

When neurotransmitters reach the postsynaptic neuron of an excitatory synapse, these molecules can bind to two possible types of receptors that are clustered in a protein-rich portion of the postsynaptic cytoskeleton called the Postsynaptic density (PSD). [2] Ionotropic receptors, which are also referred to as ligand-gated ion channels, contain a transmembrane domain that acts as an ion channel and can directly open after binding of a neurotransmitter. Metabotropic receptors, which are also called G-protein-coupled receptors, act on an ion channel through the intracellular signaling of a molecule called a G protein. Each of these channels has a specific reversal potential, Erev, and each receptor is selectively permeable to particular ions that flow either into or out of the cell in order to bring the overall membrane potential to this reversal potential. [3] If a neurotransmitter binds to a receptor with a reversal potential that is higher than the threshold potential for the postsynaptic neuron, the postsynaptic cell will be more likely to generate an action potential and an excitatory postsynaptic potential will occur (EPSP). On the other hand, if the reversal potential of the receptor to which the neurotransmitter binds is lower than the threshold potential, an inhibitory postsynaptic potential will occur (IPSP). [4]
Although the receptors at an excitatory synapse strive to bring the membrane potential towards their own specific Erev, the probability that the single stimulation of an excitatory synapse will raise the membrane potential past threshold and produce an action potential is not very high. Therefore, in order to achieve threshold and generate an action potential, the postsynaptic neuron has the capacity to add up all of the incoming EPSPs based on the mechanism of summation, which can occur in time and space. Temporal summation occurs when a particular synapse is stimulated at a high frequency, which causes the postsynaptic neuron to sum the incoming EPSPs and thus increases the chance of the neuron firing an action potential. In a similar way, the postsynaptic neuron can sum together EPSPs from multiple synapses with other neurons in a process called spatial summation. [3]

Types of excitatory neurotransmitters

Acetylcholine

Acetylcholine (ACh) is an excitatory, small-molecule neurotransmitter involved in synaptic transmission at neuromuscular junctions controlling the vagus nerve and cardiac muscle fibers, as well as in the skeletal and visceral motor systems and various sites within the central nervous system. [3] This neurotransmitter crosses the synaptic cleft and binds to a variety of postsynaptic receptors depending on the species, but all of these receptors depolarize the postsynaptic membrane and thus classify ACh as an excitatory neurotransmitter. [5]

Glutamate

Glutamate is a small, amino acid neurotransmitter, and is the primary excitatory neurotransmitter at almost all synapses in the central nervous system. This molecule binds multiple postsynaptic receptors including the NMDA receptor, AMPA receptor, and kainate receptors. These receptors are all cation channels that allow positively charged ions such as Na+, K+, and sometimes Ca2+ into the postsynaptic cell, causing a depolarization that excites the neuron. [3]

Catecholamines

The catecholamines, which include Epinephrine, Norepinephrine, and Dopamine, are excitatory biogenic amine neuromodulators that are derived from the amino acid tyrosine and serve as excitatory neurotransmitters at various locations in the central nervous system as well as the peripheral nervous system. Epinephrine and norepinephrine, also called adrenaline and noradrenaline, respectively, bind a number of G-protein-coupled receptors that induce their depolarizing effects on the postsynaptic cell in various ways, including activating and inactivating certain K+ channels. Epinephrine is found in the lateral tegmental system, medulla, hypothalamus, and thalamus of the central nervous system, but their function is not fully understood. Norepinephrine is found in the brain stem and is involved in sleep and wakefulness, feeding behavior, and attention. Dopamine binds to G-protein-coupled receptors in many areas of the brain, especially the corpus striatum where it mediates the synaptic transmission that underlies the coordination of body movements. [3]

Serotonin

Serotonin is an excitatory neurotransmitter that regulates sleep and wakefulness and is found in neurons of the raphe region of the pons and upper brain stem, which extend into the forebrain. Serotonin binds a number of receptors, including the 5-HT3 receptors, which are ligand-gated ion channels that allow the passage of cations in order to depolarize the membrane potential of the postsynaptic neuron that they reside on. [3] Levels of serotonin activity that are lower than normal have been linked to a variety of symptoms, especially depression, which is why many antidepressant drugs act to increase serotonin activity. [6]

Histamine

Histamine acts as an excitatory neurotransmitter by binding G-protein coupled receptors in neurons of the hypothalamus. These neurons project into many regions of the brain and spinal cord, allowing histamine to mediate attention, arousal, and allergic responses. [3] Of the four types of histamine receptors (H1 - H4), H3 is found in the central nervous system and is responsible for regulating histamine effects on neurotransmission. [7]

Disease

Excitatory synapses have a fundamental role in information processing within the brain and throughout the peripheral nervous system. Usually situated on dendritic spines, or neuronal membrane protrusions on which glutamate receptors and postsynaptic density components are concentrated, excitatory synapses aid in the electrical transmission of neuronal signals. [1] The physical morphology of synapses is crucial in understanding their function, and it is well documented that the inappropriate loss of synaptic stability leads to the disruption of neuronal circuits and the resulting neurological diseases. Although there are innumerable different causes for different neurodegenerative illnesses, such as genetic dispositions or mutations, the normal aging process, parasitic and viral causes, or drug use, many can be traced back to dysfunctional signaling between the neurons themselves, often at the synapse. [3]

Excitotoxicity

Pathophysiology

Since glutamate is the most common excitatory neurotransmitter involved in synaptic neuronal transmission, it follows that disruptions in the normal functioning of these pathways can have severe detrimental effects on the nervous system. A major source of cellular stress is related to glutaminergic overstimulation of a postsynaptic neuron via excessive activation of glutamate receptors (i.e., NMDA and AMPA receptors), a process known as excitotoxicity, which was first discovered accidentally by D. R. Lucas and J. P. Newhouse in 1957 during experimentation on sodium-fed lab mice. [3]
Under normal conditions, extracellular glutamate levels are held under strict control by surrounding neuronal and glial cell membrane transporters, rising to a concentration of about 1 mM and quickly falling to resting levels. [8] These levels are maintained via the recycling of glutamate molecules in the neuronal-glial cell process known as the glutamate–glutamine cycle, in which glutamate is synthesized from its precursor glutamine in a controlled manner in order to maintain an adequate supply of the neurotransmitter. [3] However, when glutamate molecules in the synaptic cleft cannot be degraded or reused, often due to dysfunction of the glutamate–glutamine cycle, the neuron becomes significantly overstimulated, leading to a neuronal cell death pathway known as apoptosis. Apoptosis occurs primarily via the increased intracellular concentrations of calcium ions, which flow into the cytosol through the activated glutamate receptors and lead to the activation of phospholipases, endonucleases, proteases, and thus the apoptotic cascade. Additional sources of neuronal cell death related to excitotoxicity involve energy rundown in the mitochondria and increased concentrations of reactive oxygen and nitrogen species within the cell. [3]

Treatment

Excitotoxic mechanisms are often involved in other conditions leading to neuronal damage, including hypoglycemia, trauma, stroke, seizures, and many neurodegenerative diseases, and thus have important implications in disease treatment. Recent studies have been performed that incorporate glutamate receptor antagonists and excitotoxic cascade disruptors in order to decrease stimulation of postsynaptic neurons, although these treatments are still undergoing active research. [9]
Alzheimer's disease (AD) is the most common form of neurodegenerative dementia, or loss of brain function, and was first described by German psychiatrist and neuropathologist Alois Alzheimer in 1907. 9. [10] Diagnosis of the disease often stems from clinical observation as well as analysis of family history and other risk factors, and often includes symptoms such as memory impairment and problems with language, decision-making, judgment, and personality. [11] The primary neurological phenomena that lead to the above symptoms are often related to signaling at excitatory synapses, often due to excitotoxicity, and stem from the presence of amyloid plaques and neurofibrillary tangles, as well as neuronal cell death and synaptic pruning. The principle drug treatments on the market deal with antagonizing glutamate (NMDA) receptors at neuronal synapses, and inhibiting the activity of acetylcholinesterase. This treatment aims to limit the apoptosis of cerebral neurons caused by various pathways related to excitotoxicity, free radicals, and energy rundown. A number of labs are currently focusing on the prevention of amyloid plaques and other AD symptoms, often via the use of experimental vaccines, although this area of research is yet in its infancy. [10]
Histological brain sample of the Substantia Nigra in Parkinson's disease, showing the presence of Lewy bodies and other signs of neurodegeneration. Histological sample of Substantia nigra in Parkinson's disease.jpg
Histological brain sample of the Substantia Nigra in Parkinson's disease, showing the presence of Lewy bodies and other signs of neurodegeneration.
Parkinson's disease (PD) is a neurodegenerative disease resulting from the apoptosis of dopaminergic neurons in the central nervous system, especially the substantia nigra, as well as heightened response to the excitatory neurotransmitter, glutamate (i.e., excitotoxicity). [12] While the most obvious symptoms are related to motor skills, prolonged progression of the disease can lead to cognitive and behavioral problems as well as dementia. Although the mechanism of apoptosis in the brain is not entirely clear, speculation associates cell death with abnormal accumulation of ubiquitinated proteins in cell occlusions known as Lewy bodies, as well as hyperstimulation of neuronal NMDA receptors with excessive glutamate neurotransmitter via the aforementioned pathway. [12] Like Alzheimer's, Parkinson's Disease lacks a cure. Therefore, in addition to lifestyle changes and surgery, the goal of pharmaceutical drugs used in the treatment of PD patients is to control symptoms and limit, when possible, the progression of the disease. Levodopa (L-DOPA), the most widely used treatment of PD, is converted to dopamine in the body and helps to relieve the effect of decreased dopaminergic neurons in the central nervous system. Other dopamine agonists have been administered to patients in an effort to mimic dopamine’s effect at excitatory synapses, binding its receptors and causing the desired postsynaptic response. [13]

See also

Related Research Articles

<span class="mw-page-title-main">Neuron</span> Electrically excitable cell found in the nervous system of animals

A neuron, neurone, or nerve cell is an excitable cell that fires electric signals called action potentials across a neural network in the nervous system. Neurons communicate with other cells via synapses, which are specialized connections that commonly use minute amounts of chemical neurotransmitters to pass the electric signal from the presynaptic neuron to the target cell through the synaptic gap.

<span class="mw-page-title-main">Chemical synapse</span> Biological junctions through which neurons signals can be sent

Chemical synapses are biological junctions through which neurons' signals can be sent to each other and to non-neuronal cells such as those in muscles or glands. Chemical synapses allow neurons to form circuits within the central nervous system. They are crucial to the biological computations that underlie perception and thought. They allow the nervous system to connect to and control other systems of the body.

An inhibitory postsynaptic potential (IPSP) is a kind of synaptic potential that makes a postsynaptic neuron less likely to generate an action potential. The opposite of an inhibitory postsynaptic potential is an excitatory postsynaptic potential (EPSP), which is a synaptic potential that makes a postsynaptic neuron more likely to generate an action potential. IPSPs can take place at all chemical synapses, which use the secretion of neurotransmitters to create cell-to-cell signalling. EPSPs and IPSPs compete with each other at numerous synapses of a neuron. This determines whether an action potential occurring at the presynaptic terminal produces an action potential at the postsynaptic membrane. Some common neurotransmitters involved in IPSPs are GABA and glycine.

<span class="mw-page-title-main">Excitatory postsynaptic potential</span> Process causing temporary increase in postsynaptic potential

In neuroscience, an excitatory postsynaptic potential (EPSP) is a postsynaptic potential that makes the postsynaptic neuron more likely to fire an action potential. This temporary depolarization of postsynaptic membrane potential, caused by the flow of positively charged ions into the postsynaptic cell, is a result of opening ligand-gated ion channels. These are the opposite of inhibitory postsynaptic potentials (IPSPs), which usually result from the flow of negative ions into the cell or positive ions out of the cell. EPSPs can also result from a decrease in outgoing positive charges, while IPSPs are sometimes caused by an increase in positive charge outflow. The flow of ions that causes an EPSP is an excitatory postsynaptic current (EPSC).

In neuroscience, a silent synapse is an excitatory glutamatergic synapse whose postsynaptic membrane contains NMDA-type glutamate receptors but no AMPA-type glutamate receptors. These synapses are named "silent" because normal AMPA receptor-mediated signaling is not present, rendering the synapse inactive under typical conditions. Silent synapses are typically considered to be immature glutamatergic synapses. As the brain matures, the relative number of silent synapses decreases. However, recent research on hippocampal silent synapses shows that while they may indeed be a developmental landmark in the formation of a synapse, that synapses can be "silenced" by activity, even once they have acquired AMPA receptors. Thus, silence may be a state that synapses can visit many times during their lifetimes.

<span class="mw-page-title-main">Graded potential</span> Changes in membrane potential varying in size

Graded potentials are changes in membrane potential that vary according to the size of the stimulus, as opposed to being all-or-none. They include diverse potentials such as receptor potentials, electrotonic potentials, subthreshold membrane potential oscillations, slow-wave potential, pacemaker potentials, and synaptic potentials. The magnitude of a graded potential is determined by the strength of the stimulus. They arise from the summation of the individual actions of ligand-gated ion channel proteins, and decrease over time and space. They do not typically involve voltage-gated sodium and potassium channels, but rather can be produced by neurotransmitters that are released at synapses which activate ligand-gated ion channels. They occur at the postsynaptic dendrite in response to presynaptic neuron firing and release of neurotransmitter, or may occur in skeletal, smooth, or cardiac muscle in response to nerve input. These impulses are incremental and may be excitatory or inhibitory.

<span class="mw-page-title-main">Neuromuscular junction</span> Junction between the axon of a motor neuron and a muscle fiber

A neuromuscular junction is a chemical synapse between a motor neuron and a muscle fiber.

<span class="mw-page-title-main">End-plate potential</span> Voltages associated with muscle fibre

End plate potentials (EPPs) are the voltages which cause depolarization of skeletal muscle fibers caused by neurotransmitters binding to the postsynaptic membrane in the neuromuscular junction. They are called "end plates" because the postsynaptic terminals of muscle fibers have a large, saucer-like appearance. When an action potential reaches the axon terminal of a motor neuron, vesicles carrying neurotransmitters are exocytosed and the contents are released into the neuromuscular junction. These neurotransmitters bind to receptors on the postsynaptic membrane and lead to its depolarization. In the absence of an action potential, acetylcholine vesicles spontaneously leak into the neuromuscular junction and cause very small depolarizations in the postsynaptic membrane. This small response (~0.4mV) is called a miniature end plate potential (MEPP) and is generated by one acetylcholine-containing vesicle. It represents the smallest possible depolarization which can be induced in a muscle.

Molecular neuroscience is a branch of neuroscience that observes concepts in molecular biology applied to the nervous systems of animals. The scope of this subject covers topics such as molecular neuroanatomy, mechanisms of molecular signaling in the nervous system, the effects of genetics and epigenetics on neuronal development, and the molecular basis for neuroplasticity and neurodegenerative diseases. As with molecular biology, molecular neuroscience is a relatively new field that is considerably dynamic.

The induction of NMDA receptor-dependent long-term potentiation (LTP) in chemical synapses in the brain occurs via a fairly straightforward mechanism. A substantial and rapid rise in calcium ion concentration inside the postsynaptic cell is most possibly all that is required to induce LTP. But the mechanism of calcium delivery to the postsynaptic cell in inducing LTP is more complicated.

Postsynaptic potentials are changes in the membrane potential of the postsynaptic terminal of a chemical synapse. Postsynaptic potentials are graded potentials, and should not be confused with action potentials although their function is to initiate or inhibit action potentials. They are caused by the presynaptic neuron releasing neurotransmitters from the terminal bouton at the end of an axon into the synaptic cleft. The neurotransmitters bind to receptors on the postsynaptic terminal, which may be a neuron, or a muscle cell in the case of a neuromuscular junction. These are collectively referred to as postsynaptic receptors, since they are on the membrane of the postsynaptic cell.

<span class="mw-page-title-main">Neurotransmission</span> Impulse transmission between neurons

Neurotransmission is the process by which signaling molecules called neurotransmitters are released by the axon terminal of a neuron, and bind to and react with the receptors on the dendrites of another neuron a short distance away. A similar process occurs in retrograde neurotransmission, where the dendrites of the postsynaptic neuron release retrograde neurotransmitters that signal through receptors that are located on the axon terminal of the presynaptic neuron, mainly at GABAergic and glutamatergic synapses.

<span class="mw-page-title-main">Synapse</span> Structure connecting neurons in the nervous system

In the nervous system, a synapse is a structure that permits a neuron to pass an electrical or chemical signal to another neuron or to the target effector cell.

<span class="mw-page-title-main">Synaptic potential</span> Potential difference across the postsynaptic membrane

Synaptic potential refers to the potential difference across the postsynaptic membrane that results from the action of neurotransmitters at a neuronal synapse. In other words, it is the “incoming” signal that a neuron receives. There are two forms of synaptic potential: excitatory and inhibitory. The type of potential produced depends on both the postsynaptic receptor, more specifically the changes in conductance of ion channels in the post synaptic membrane, and the nature of the released neurotransmitter. Excitatory post-synaptic potentials (EPSPs) depolarize the membrane and move the potential closer to the threshold for an action potential to be generated. Inhibitory postsynaptic potentials (IPSPs) hyperpolarize the membrane and move the potential farther away from the threshold, decreasing the likelihood of an action potential occurring. The Excitatory Post Synaptic potential is most likely going to be carried out by the neurotransmitters glutamate and acetylcholine, while the Inhibitory post synaptic potential will most likely be carried out by the neurotransmitters gamma-aminobutyric acid (GABA) and glycine. In order to depolarize a neuron enough to cause an action potential, there must be enough EPSPs to both depolarize the postsynaptic membrane from its resting membrane potential to its threshold and counterbalance the concurrent IPSPs that hyperpolarize the membrane. As an example, consider a neuron with a resting membrane potential of -70 mV (millivolts) and a threshold of -50 mV. It will need to be raised 20 mV in order to pass the threshold and fire an action potential. The neuron will account for all the many incoming excitatory and inhibitory signals via summative neural integration, and if the result is an increase of 20 mV or more, an action potential will occur.

Gliotransmitters are chemicals released from glial cells that facilitate neuronal communication between neurons and other glial cells. They are usually induced from Ca2+ signaling, although recent research has questioned the role of Ca2+ in gliotransmitters and may require a revision of the relevance of gliotransmitters in neuronal signalling in general.

<span class="mw-page-title-main">Summation (neurophysiology)</span>

Summation, which includes both spatial summation and temporal summation, is the process that determines whether or not an action potential will be generated by the combined effects of excitatory and inhibitory signals, both from multiple simultaneous inputs, and from repeated inputs. Depending on the sum total of many individual inputs, summation may or may not reach the threshold voltage to trigger an action potential.

Cellular neuroscience is a branch of neuroscience concerned with the study of neurons at a cellular level. This includes morphology and physiological properties of single neurons. Several techniques such as intracellular recording, patch-clamp, and voltage-clamp technique, pharmacology, confocal imaging, molecular biology, two photon laser scanning microscopy and Ca2+ imaging have been used to study activity at the cellular level. Cellular neuroscience examines the various types of neurons, the functions of different neurons, the influence of neurons upon each other, and how neurons work together.

<span class="mw-page-title-main">Active zone</span>

The active zone or synaptic active zone is a term first used by Couteaux and Pecot-Dechavassinein in 1970 to define the site of neurotransmitter release. Two neurons make near contact through structures called synapses allowing them to communicate with each other. As shown in the adjacent diagram, a synapse consists of the presynaptic bouton of one neuron which stores vesicles containing neurotransmitter, and a second, postsynaptic neuron which bears receptors for the neurotransmitter, together with a gap between the two called the synaptic cleft. When an action potential reaches the presynaptic bouton, the contents of the vesicles are released into the synaptic cleft and the released neurotransmitter travels across the cleft to the postsynaptic neuron and activates the receptors on the postsynaptic membrane.

In neuroscience, synaptic scaling is a form of homeostatic plasticity, in which the brain responds to chronically elevated activity in a neural circuit with negative feedback, allowing individual neurons to reduce their overall action potential firing rate. Where Hebbian plasticity mechanisms modify neural synaptic connections selectively, synaptic scaling normalizes all neural synaptic connections by decreasing the strength of each synapse by the same factor, so that the relative synaptic weighting of each synapse is preserved.

Anoxic depolarization is a progressive and uncontrollable depolarization of neurons during stroke or brain ischemia in which there is an inadequate supply of blood to the brain. Anoxic depolarization is induced by the loss of neuronal selective membrane permeability and the ion gradients across the membrane that are needed to support neuronal activity. Normally, the Na+/K+-ATPase pump maintains the transmembrane gradients of K+ and Na+ ions, but with anoxic brain injury, the supply of energy to drive this pump is lost. The hallmarks of anoxic depolarization are increased concentrations of extracellular K+ ions, intracellular Na+ and Ca2+ ions, and extracellular glutamate and aspartate. Glutamate and aspartate are normally present as the brain's primary excitatory neurotransmitters, but high concentrations activate a number of downstream apoptotic and necrotic pathways. This results in neuronal dysfunction and brain death.

References

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  2. 1 2 Chua, Kindler; Boykin, Jahn (2010-03-03). "Architecture of an Excitatory Synapse". Journal of Cell Science. 123 (6): 819–823. doi:10.1242/jcs.052696. hdl: 11858/00-001M-0000-0012-D5F7-3 . PMID   20200227. S2CID   13491894.
  3. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 D. Purves; et al. (2008). Neuroscience, 4th ed. Sunderland, Massachusetts: Sinauer Associates, Inc.
  4. ↑ Williams, S. Mark; McNamara, James O.; Lamantia, Anthony-Samuel; Katz, Lawrence C.; Fitzpatrick, David; Augustine, George J.; Purves, Dale (2001). "Excitatory and Inhibitory Postsynaptic Potentials". Sinauer Associates, Inc.
  5. ↑ J. Rand (2007). "Acetylcholine".
  6. ↑ Stephen Gislason (1995). "Neurotransmitter - Serotonin". Brain Mind Center at Alpha Online.
  7. ↑ R. Bowen (2008). "Histamine and Histamine Receptors".
  8. ↑ "Excitotoxicity and Cell Damage". 2010.
  9. ↑ M. Aarts; M. Tymianski (2003-09-15). "Novel treatment of excitotoxicity: targeted disruption of intracellular signalling from glutamate receptors". Biochemical Pharmacology. 66 (6): 877–886. doi:10.1016/S0006-2952(03)00297-1. PMID   12963474.
  10. 1 2 J. Tavee; P. Sweeney. "Alzheimer's Disease".
  11. ↑ "Alzheimer's Disease". 2010-10-04.
  12. ↑ "Parkinson's Disease". 2011.
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