thumb|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 depolarizes the membrane of the postsynaptic cell, and thus increases the probability of triggering an action potential in that cell. The postsynaptic cella muscle cell, a glandular cell or another neurontypically receives input signals through many excitatory and many inhibitory synapses. If the total of excitatory influences exceeds that of the inhibitory influences and the resulting depolarization exceeds the threshold level, the postsynaptic cell will be activated. If the postsynaptic cell is a neuron it will generate a new action potential at its axon hillock, thus transmitting the information to yet another cell. If it is a muscle cell, it will contract. If it is a gland cell, it will release its product (e.g., hormone).

In an excitatory synapse, the electric response of the postsynaptic membrane to a single action potential in the presynaptic neuron 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.

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. 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.

:Although the receptors at an excitatory synapse strive to bring the membrane potential towards their own specific E<sub>rev</sub>, 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.

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<sup>+</sup>, K<sup>+</sup>, and sometimes Ca<sup>2+</sup> into the postsynaptic cell, causing a depolarization that excites the neuron.

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.

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. 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.

: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. 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. 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. 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.

See also

  • Inhibitory synapse
  • Neurotransmission
  • Neuroscience
  • Synaptogenesis
  • Electrophysiology
  • Neurotoxicity

References