neurologic disorders
Neurotransmission
Transmission
Impulse transmission is chemical, caused by release of specific neurotransmitters from the nerve ending (terminal). Neurotransmitters diffuse across the synaptic cleft and bind briefly to specific receptors on the adjoining neuron or effector cell. Depending on the receptor, the response may be excitatory or inhibitory. Usually, neurons do not touch each other; instead, they communicate through the transmission of neurotransmitters across the synapses. Under some conditions, neurons near each other can communicate using electrical impulses across a gap junction.. The nerve cell body produces enzymes that synthesize most neurotransmitters, which are stored in vesicles at the nerve terminal (see figure Neurotransmission ). The amount in one vesicle (usually several thousand molecules) is a quantum. A membrane action potential arriving at the terminal opens axonal calcium channels; calcium inflow releases neurotransmitter molecules from many vesicles by fusing the vesicle membranes to the nerve terminal membrane. Membrane fusion generates an opening through which the molecules are expelled into the synaptic cleft via exocytosis. One type of synapse, the electrical synapse, does not involve neurotransmitters; ion channels directly connect the cytoplasm of the presynaptic and postsynaptic neurons. This type of transmission is the fastest. Excitatory and inhibitory signals The reaction triggered by neurotransmitter release can either excite or activate the postsynaptic neuron or inhibit or block its activity. Postsynaptic neurons receive multiple neurotransmitter signals and electrical signals from many neurons. The receiving neuron ultimately adds the inputs together, and if more excitatory signals are received, the neuron fires and sends signals to other neurons. If the sum of the signals are inhibitory, the neuron does not fire and does not influence the activity of other neurons. This adding up of responses is called summation. Neurotransmitters thus facilitate rapid communication between neurons by changing the firing of the action potential. Other forms of summation include Spatial summation: When multiple impulses are received on different locations of the neuron and the neuron then sums them up Temporal summation: When impulses are received within a short period of time and are then added together For a neuron to generate a signal and fire, it must reach a threshold potential. A threshold potential is produced by a net increase in sodium influx into the cell during the exchange of sodium and potassium ions. When enough sodium enters the cell, the threshold is reached; when the threshold is reached, an action potential is fired; it travels along the neuron's membrane. The threshold must be reached for an action potential to be generated. Action potentials open the axonal calcium (Ca) channels (not shown). Ca++activates release of neurotransmitters (NT) from vesicles where they are stored. NT molecules fill the synaptic cleft. Some bind to postsynaptic receptors, initiating a response. The others are pumped back into the axon and stored or diffuse into the surrounding tissues. The amount of neurotransmitters in the terminal is typically independent of nerve activity and kept relatively constant by modifying uptake of neurotransmitter precursors or the activity of enzymes involved in neurotransmitter synthesis or destruction. Stimulation of presynaptic receptors can decrease presynaptic neurotransmitter synthesis, and blockade can increase it. The neurotransmitter-receptor interaction must be terminated quickly to end the continued action of the neurotransmitter and/or to allow rapid, repeated activation of receptors. One of the following can happen to neurotransmitters that have interacted with receptors: They can be quickly pumped back into the presynaptic nerve terminals by active, ATP-dependent processes (reuptake) for recycling or destruction. They can be eliminated by enzymes near the receptors. They can diffuse into the surrounding area and be removed. Neurotransmitters taken up by the nerve terminals are repackaged in granules or vesicles in the axon terminal for reuse. Malfunction of these processes can result in clinical disease. For example, loss of memory in Alzheimer disease is postulated to involve insufficiency of the neurotransmitter acetylcholine in synapses, which mediates the laying down of new memories. Certain drugs (eg,donepezil, galanthamine,rivastigmine) block the enzyme acetylcholinesterase (which breaks down acetylcholine) and thus increase the amount of acetylcholine in the synapse. As a result, memory function may improve. Some types of single neurons can release two or more different neurotransmitters (called cotransmission)—for example, acetylcholine and glutamate. Multiple neurotransmitters may act on a single postsynaptic neuron or affect multiple postsynaptic neurons. Cotransmission allows for intricate communication among neurons to control different events in the CNS and the peripheral nervous system (PNS). Neurotransmitters can also facilitate more long-term changes that involve additional pathways such as changes in the activity of genes and proteins. 