Interneuronal Synapses

Action potentials and axons terminate at synaptic connections with other neurons or effector cells such as muscle or gland. Final branch portions of axons are thin with swollen synaptic terminals known as boutons. Some axons may have multiple boutons, each one forming a synapse. Generally, synapses form between the axon terminal and another neuron's dendrite, although axon-cell body, axon-axon, and dendrite-dendrite synapses also occur. Many, even most, dendritic synapses occur on dendritic "spines"knobby dendritic protuberances.

Two modes of synaptic signaling have been recognized: electrical and chemical. At electrical synapses, currents generated by an impulse of the presynaptic nerve terminal spread directly to the next neuron through a low resistance pathway (which may be networks of extracellular protein filaments known as "synapsin"). The sites for electrical communication between cells have been identified in electron micrographs as gap junctions in which the usual intercellular space of several tens of nanometers is reduced to about two nanometers. There appear to be a huge number of electrical synapses in mammalian brain (estimated to be as high as 80 percent of all synapses), but because of difficulties in isolation, characterization, and inability to study them by pharmacological manipulation, their significance remains unknown. Chemical synapses have been extensively studied.

At chemical synapses the fluid gap between presynaptic and postsynaptic membranes prevents a direct spread of current and the lack of an electrical connection between neurons. The synaptic bouton contains large quantities of spherical vesicles (about 50 nanometers diameter) which contain neurotransmitter molecules. Acetylcholine, norepinephrine, serotonin, dopamine, gamma amino butyric acid (GABA) and various peptides and amines have been identified as neurotransmitters. Some are excitatory while others (i.e. GABA) are inhibitory.

Figure 4.1: Neuronal organization: 1) Branching dendrites (top) entering cell body or perikaryon; branching axons exiting at bottom. 2) Axons forming synapses on dendrites and cell body. 3) Axon surrounded by 100 layers of myelin which increases conduction velocity; structures visible in axon include mitochondria, neurotransmitter vesicles, and microtubules. 4) Synaptic cleft; neurotransmitter vesicles (top right) fuse with membrane as they are released. By Paul Jablonka.

Figure 4.1: Neuronal organization: 1) Branching dendrites (top) entering cell body or perikaryon; branching axons exiting at bottom. 2) Axons forming synapses on dendrites and cell body. 3) Axon surrounded by 100 layers of myelin which increases conduction velocity; structures visible in axon include mitochondria, neurotransmitter vesicles, and microtubules. 4) Synaptic cleft; neurotransmitter vesicles (top right) fuse with membrane as they are released. By Paul Jablonka.

Figure 4.2: Schematic diagram of brain functional components. By Paul Jablonka.

The sequence of events liberating neurotransmitter molecules from nerve endings is remarkably uniform at all synapses. Transmitter molecules are stored inside presynaptic nerve terminals in small vesicles that are analogous to the secretory granules of gland cells. The amount of neurotransmitter in one vesicle is considered a "quantum" and in neuromuscular synapses each quantum consists of one thousand to five thousand molecules of acetylcholine. Each action potential reaching the presynaptic terminal releases a number of vesicle quanta ranging from a few to several hundred. The coupling mechanism between the action potential and vesicle release involves both calcium and the cytoskeleton. As an action potential impulse arrives at the presynaptic nerve terminal, calcium ions enter the cytoplasm through the membrane by way of voltage gated channels. In presynaptic nerve terminals, inward ionic current of the action potential is thus carried partially by sodium and partially by calcium. Free calcium in the cytoplasm of the terminal causes vesicles to fuse with the surface membrane and to expel their contents. The mechanisms by which calcium triggers the release of vesicles from the presynaptic terminal is not clearly understood, however cytoskeletal proteins including contractile actin, myosin, and other filamentous proteins are involved. Calcium mediates dynamic contractile activities in flagella and skeletal muscle and appears to trigger cytoskeletal expulsion of neurotransmitters from nerve terminals.

After release, transmitter molecules diffuse across the synaptic cleft and bind reversibly with the postsynaptic membrane receptors. The distance between the two membranes is sufficiently small such that the diffusion takes about a millisecond-a relatively slow event compared to switching in semiconductors. Whenever a transmitter molecule binds to the postsynaptic membrane, it causes a small voltage change in the postsynaptic membrane called the miniature endplate potential which can be either excitatory or inhibitory depending on the neurotransmitter molecule and postsynaptic receptor. In the resting state there are spontaneous releases of individual vesicles causing a background rate of miniature end plate potentials which are below the threshold for depolarization of the postsynaptic cell.

Specific binding of neurotransmitter molecules to post synaptic receptors changes the membrane permeability to specific ions which produce localized receptor potentials which are either excitatory or inhibitory. The post synaptic membrane "integrates" the local receptor potentials spatially and temporally such that when a "threshold" is exceeded, signals propagate in the post synaptic dendrite, cell body, or axon.

Whether the response is excitatory or inhibitory depends on the species of ion channel carrying the synaptic current. For example, in the neuromuscular junction, acetylcholine increases post synaptic permeability to sodium and potassium, leading to an excitatory, depolarizing action potential. Post synaptic acetycholine activated channels open for one to two milliseconds and allow a net entry of about 2 x 104 ions. Other synaptic channels stay open for tens of milliseconds and pass 105 ions or more. Still other post synaptic receptors couple directly to cytoskeletal changes and do not involve ionic conductance at all. At inhibitory synapses, GABA may increase permeability to chloride ion, driving the membrane potential away from threshold: Inhibition may also occur pre-synaptically in which case release of excitatory neurotransmitter is prevented. By combining multiple inputs, synapses "compute" to determine their output.

Nerve cells influence each other by either excitation, producing impulses in another cell, or by inhibition, tending to prevent impulses from arising in an adjacent cell. Lateral inhibition also occurs; activity in a group of active axons inhibits firing in nearby fibers—an apparent sharpening or focusing mechanism. A neuron receives many excitatory and inhibitory inputs from other cells (convergence) and in turn supplies many others (divergence). The process whereby neurons combine together all of their incoming signals is known as integration. Thus each cell must integrate a multitude of synaptic inputs (up to 200,000 synapses per neuron) to determine its own output. Additional levels of processing at dendritic branch points, dendritic spines, active nodes between myelin sheaths, and changes in synaptic efficacy illustrate the complexity at the level of individual neurons. Rather than a simple switch, each neuron is more like a computer. The intraneuronal cytoskeleton is the nervous system within the nervous system.

0 0

Post a comment