Synaptosome

Last updated
Synaptosome
Schematic of isolated synaptosome.jpg
Schematic of isolated synaptosome with numerous small synaptic vesicles, two dense-core vesicles, one mitochondrion and a patch of postsynaptic membrane attached to the presynaptic active zone
Identifiers
MeSH D013574
TH H2.00.06.2.00033
Anatomical terms of neuroanatomy

A synaptosome is an isolated synaptic terminal from a neuron. Synaptosomes are obtained by mild homogenization of nervous tissue under isotonic conditions and subsequent fractionation using differential and density gradient centrifugation. Liquid shear detaches the nerve terminals from the axon and the plasma membrane surrounding the nerve terminal particle reseals. Synaptosomes are osmotically sensitive, contain numerous small clear synaptic vesicles, sometimes larger dense-core vesicles and frequently one or more small mitochondria. They carry the morphological features and most of the chemical properties of the original nerve terminal. Synaptosomes isolated from mammalian brain often retain a piece of the attached postsynaptic membrane, facing the active zone.

Synaptosomes were first isolated in an attempt to identify the subcellular compartment corresponding to the fraction of so-called bound acetylcholine that remains when brain tissue is homogenized in iso-osmotic sucrose. Particles containing acetylcholine and its synthesizing enzyme choline acetyltransferase were originally isolated by Hebb and Whittaker (1958) [1] at the Agricultural Research Council, Institute of Animal Physiology, Babraham, Cambridge, UK. In a collaborative study with the electron microscopist George Gray from University College London, Victor P. Whittaker eventually showed that the acetylcholine-rich particles derived from guinea-pig cerebral cortex were synaptic vesicle-rich pinched-off nerve terminals. [2] [3] Whittaker coined the term synaptosome to describe these fractionation-derived particles and shortly thereafter synaptic vesicles could be isolated from lysed synaptosomes. [4] [5] [6]

Synaptosomes are commonly used to study synaptic transmission in the test tube because they contain the molecular machinery necessary for the uptake, storage, and release of neurotransmitters. In addition they have become a common tool for drug testing. They maintain a normal membrane potential, contain presynaptic receptors, translocate metabolites and ions, and when depolarized, release multiple neurotransmitters (including acetylcholine, amino acids, catecholamines, and peptides) in a Ca2+-dependent manner. Synaptosomes isolated from the whole brain or certain brain regions are also useful models for studying structure-function relationships in synaptic vesicle release. [7] Synaptosomes can also be isolated from tissues other than brain such as spinal cord, retina, myenteric plexus or the electric ray electric organ. [8] [9] Synaptosomes may be used to isolate postsynaptic densities [10] or the presynaptic active zone with attached synaptic vesicles. [11] Accordingly, various subproteomes of isolated synaptosomes, such as synaptic vesicles, synaptic membranes, or postsynaptic densities can now be studied by proteomic techniques, leading to a deeper understanding of the molecular machinery of brain neurotransmission and neuroplasticity. [12] [11] [13] [14]

Related Research Articles

<span class="mw-page-title-main">Neurotransmitter</span> Chemical substance that enables neurotransmission

A neurotransmitter is a signaling molecule secreted by a neuron to affect another cell across a synapse. The cell receiving the signal, or target cell, may be another neuron, but could also be a gland or muscle cell.

<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.

<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).

<span class="mw-page-title-main">Excitatory synapse</span> Sort of synapse

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.

<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">Synaptic vesicle</span> Neurotransmitters that are released at the synapse

In a neuron, synaptic vesicles store various neurotransmitters that are released at the synapse. The release is regulated by a voltage-dependent calcium channel. Vesicles are essential for propagating nerve impulses between neurons and are constantly recreated by the cell. The area in the axon that holds groups of vesicles is an axon terminal or "terminal bouton". Up to 130 vesicles can be released per bouton over a ten-minute period of stimulation at 0.2 Hz. In the visual cortex of the human brain, synaptic vesicles have an average diameter of 39.5 nanometers (nm) with a standard deviation of 5.1 nm.

<span class="mw-page-title-main">End-plate potential</span>

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.

Synaptogenesis is the formation of synapses between neurons in the nervous system. Although it occurs throughout a healthy person's lifespan, an explosion of synapse formation occurs during early brain development, known as exuberant synaptogenesis. Synaptogenesis is particularly important during an individual's critical period, during which there is a certain degree of synaptic pruning due to competition for neural growth factors by neurons and synapses. Processes that are not used, or inhibited during their critical period will fail to develop normally later on in life.

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.

An autoreceptor is a type of receptor located in the membranes of nerve cells. It serves as part of a negative feedback loop in signal transduction. It is only sensitive to the neurotransmitters or hormones released by the neuron on which the autoreceptor sits. Similarly, a heteroreceptor is sensitive to neurotransmitters and hormones that are not released by the cell on which it sits. A given receptor can act as either an autoreceptor or a heteroreceptor, depending upon the type of transmitter released by the cell on which it is embedded.

<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">Postsynaptic density</span>

The postsynaptic density (PSD) is a protein dense specialization attached to the postsynaptic membrane. PSDs were originally identified by electron microscopy as an electron-dense region at the membrane of a postsynaptic neuron. The PSD is in close apposition to the presynaptic active zone and ensures that receptors are in close proximity to presynaptic neurotransmitter release sites. PSDs vary in size and composition among brain regions, and have been studied in great detail at glutamatergic synapses. Hundreds of proteins have been identified in the postsynaptic density, including glutamate receptors, scaffold proteins, and many signaling molecules.

<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.

Neurotransmitter transporters are a class of membrane transport proteins that span the cellular membranes of neurons. Their primary function is to carry neurotransmitters across these membranes and to direct their further transport to specific intracellular locations. There are more than twenty types of neurotransmitter transporters.

<span class="mw-page-title-main">Vesamicol</span> Chemical compound

Vesamicol is an experimental drug, acting presynaptically by inhibiting acetylcholine (ACh) uptake into synaptic vesicles and reducing its release. Vesamicol may have applications for the treatment of adenocarcinoma in situ of the lung.

<span class="mw-page-title-main">Axon terminal</span>

Axon terminals are distal terminations of the telodendria (branches) of an axon. An axon, also called a nerve fiber, is a long, slender projection of a nerve cell, or neuron, that conducts electrical impulses called action potentials away from the neuron's cell body, or soma, in order to transmit those impulses to other neurons, muscle cells or glands.

<span class="mw-page-title-main">Synapsin I</span> Protein-coding gene in the species Homo sapiens

Synapsin I, is the collective name for Synapsin Ia and Synapsin Ib, two nearly identical phosphoproteins that in humans are encoded by the SYN1 gene. In its phosphorylated form, Synapsin I may also be referred to as phosphosynaspin I. Synapsin I is the first of the proteins in the synapsin family of phosphoproteins in the synaptic vesicles present in the central and peripheral nervous systems. Synapsin Ia and Ib are close in length and almost the same in make up, however, Synapsin Ib stops short of the last segment of the C-terminal in the amino acid sequence found in Synapsin Ia.

<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.

<span class="mw-page-title-main">Victor P. Whittaker</span>

Victor Percy Whittaker was a British biochemist who pioneered studies on the subcellular fractionation of the brain. He did this by isolating synaptosomes and synaptic vesicles from the mammalian brain and demonstrating that synaptic vesicles store the neurotransmitter acetylcholine.

<span class="mw-page-title-main">Herbert Zimmermann (neuroscientist)</span> German neuroscientist (born 1944)

Herbert Zimmermann is a German neuroscientist who pioneered the studies on the biochemical, structural and functional heterogeneity of cholinergic synaptic vesicles from the electric organ of the electric ray Torpedo, and the functional and biochemical characterization of enzymes hydrolyzing extracellular nucleotides.

References

  1. Hebb CO, Whittaker VP (1958). "Intracellular distributions of acetylcholine and choline acetylase". J Physiol. 142 (1): 187–96. doi:10.1113/jphysiol.1958.sp006008. PMC   1356703 . PMID   13564428.
  2. Gray EG, Whittaker VP (1960). The isolation of synaptic vesicles from the central nervous system. J Physiol (London) 153: 35P-37P.
  3. Gray EG, Whittaker VP (January 1962). "The isolation of nerve endings from brain: an electron-microscopic study of cell fragments derived by homogenization and centrifugation". Journal of Anatomy. 96 (Pt 1): 79–88. PMC   1244174 . PMID   13901297.
  4. Whittaker VP, Michaelson IA, Kirkland RJ (February 1964). "The separation of synaptic vesicles from nerve-ending particles ('synaptosomes')". The Biochemical Journal. 90 (2): 293–303. doi:10.1042/bj0900293. PMC   1202615 . PMID   5834239.
  5. Whittaker VP (1965). "The application of subcellular fractionation techniques to the study of brain function". Progress in Biophysics and Molecular Biology. 15: 39–96. doi: 10.1016/0079-6107(65)90004-0 . PMID   5338099.
  6. Zimmermann, Herbert (2018). "Victor P. Whittaker: The Discovery of the Synaptosome and Its Implications". Synaptosomes. Neuromethods. Vol. 141. pp. 9–26. doi:10.1007/978-1-4939-8739-9_2. ISBN   978-1-4939-8738-2.
  7. Ivannikov, M.; et al. (2013). "Synaptic vesicle exocytosis in hippocampal synaptosomes correlates directly with total mitochondrial volume". J. Mol. Neurosci. 49 (1): 223–230. doi:10.1007/s12031-012-9848-8. PMC   3488359 . PMID   22772899.
  8. Whittaker VP (1993). "Thirty years of synaptosome research". J Neurocytol. 22 (9): 735–742. doi:10.1007/bf01181319. PMID   7903689. S2CID   138747.
  9. Breukel AI, Besselsen E, Ghijsen WE (1997). Synaptosomes. A model system to study release of multiple classes of neurotransmitters. Methods in Molecular Biology. Vol. 72. pp. 33–47. doi:10.1385/0-89603-394-5:33. ISBN   0-89603-394-5. PMID   9249736.
  10. Carlin RK, Grab DJ, Cohen RS, Siekevitz P (September 1980). "Isolation and characterization of postsynaptic densities from various brain regions: enrichment of different types of postsynaptic densities". The Journal of Cell Biology. 86 (3): 831–45. doi:10.1083/jcb.86.3.831. PMC   2110694 . PMID   7410481.
  11. 1 2 Morciano M, Burré J, Corvey C, Karas M, Zimmermann H, Volknandt W (December 2005). "Immunoisolation of two synaptic vesicle pools from synaptosomes: a proteomics analysis". Journal of Neurochemistry. 95 (6): 1732–45. doi:10.1111/j.1471-4159.2005.03506.x. PMID   16269012. S2CID   33493236.
  12. Bai F, Witzmann FA (2007). "Synaptosome proteomics". Sub-cellular Biochemistry. 43: 77–98. doi:10.1007/978-1-4020-5943-8_6. ISBN   978-1-4020-5942-1. PMC   2853956 . PMID   17953392.
  13. Burré J, Beckhaus T, Schägger H, Corvey C, Hofmann S, Karas M, Zimmermann H, Volknandt W (December 2006). "Analysis of the synaptic vesicle proteome using three gel-based protein separation techniques". Proteomics. 6 (23): 6250–62. doi:10.1002/pmic.200600357. PMID   17080482. S2CID   24340148.
  14. Takamori S, Holt M, Stenius K, Lemke EA, Grønborg M, Riedel D, Urlaub H, Schenck S, Brügger B, Ringler P, Müller SA, Rammner B, Gräter F, Hub JS, De Groot BL, Mieskes G, Moriyama Y, Klingauf J, Grubmüller H, Heuser J, Wieland F, Jahn R (November 2006). "Molecular anatomy of a trafficking organelle". Cell. 127 (4): 831–46. doi:10.1016/j.cell.2006.10.030. hdl: 11858/00-001M-0000-0012-E357-D . PMID   17110340. S2CID   6703431.