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Synapse miltan chowdhury
- 1. Electrical Synapse Communication & Ephaptic Communication Prepared by MILTAN CHOWDHURY EDO15003 1
- 2. Outline •Introduction to synapse,types….. •Electrical Synaptic Communication structure,properties,Connexins and its types ,future challenges •Ephaptic Coupling communication Introduction,why?It’s role,some examples. 2
- 3. Synapse Definition The synapse has been defined as a specialized structure that mediates a functional interaction between two neurons or between a neuron and another cell type. 3
- 4. Two type of Synapse ELectrical synapse Chemical Synapse An electrical synapse is a mechanical and electrically conductive link between two neighboring neurons that is formed at a narrow gap between the pre- and postsynaptic neurons known as a gap junction. 4
- 5. • The gap is about 2-4 nm 5
- 6. 6
- 7. Difference Between Chemical and Electrical Synapse At chemical synapses, an action potential arriving at the pre-synaptic terminal triggers the exocytosis of vesicles filled with neurotransmitters , which are then released in the synaptic cleft. Transmitters diffuse and bind to specific receptors on the post-synaptic cell, where they gate (viz., open or close) ion channels either directly or indirectly, thereby affecting its membrane conductance. In this example, the opening of a ligand-gated channel triggers ionic influx in the post-synaptic cell. At electrical synapses, gap junction channels allow a direct communication between the cytoplasm of the two coupled cells. 7
- 8. 8
- 9. Connexin 9 The connexins are a family of integral membrane proteins that oligomerise to form intercellular channels that are clustered at gap junctions. These channels are specialised sites of cell-cell contact that allow the passage of ions, intracellular metabolites and messenger molecules, Gap junction channels have relatively large pores (16–20 A ˚ of diameter) (with molecular weight less than 1-2kDa) from the cytoplasm of one cell to its opposing neighbours.
- 10. Connexins(Cx) 10 Their conductances, permeability to different molecules, phosphorylation and voltage-dependence of their gating, have been found to vary. Possible communication diversity is increased further by the fact that gap junctions may be formed by the association of different connexin isoforms from apposing cells. However, in vitro studies have shown that not all possible combinations of connexins produce active channels
- 11. Connexins(Cx) Contd... The family of connexin genes comprises 21 members in the human and 20 in the mouse genome, 19 of which can be considered as orthologue pairs on the basis of their sequence. They are found in almost all vertebrate cell types, and somewhat similar proteins have been cloned from plant species. Invertebrates utilise a different family of molecules, innexins, that share a similar predicted secondary structure to the vertebrate connexins, but have no sequence identity to them 11
- 12. Connexin Types • Two sets of nomenclature have been used to identify the connexins. • The first, and most commonly used, classifies the connexin molecules according to molecular weight, such as connexin43 (abbreviated to Cx43), indicating a connexin of molecular weight close to 43kDa. • However, studies have revealed cases where clear functional homologues exist across species that have quite different molecular masses; therefore, an alternative nomenclature was proposed based on evolutionary considerations, which divides the family into two major subclasses, alpha and beta, each with a number of members . 12
- 13. Property Electrical Synapse(Gap Junctions) • Symmetrical morphology. • Bidirectional transfer of information(Pre- and postsynaptic elements physically indistinguishable Bi-directional!), but can be unidirectional. • Pre- and postsynaptic cell membranes are in close Ions can flow through these gap junctions, providing low-resistance pathway for cells without leakage to the extracellular space signal • transmission = electrotonic transmission. - Instantaneous, fast transfer from 1 cell to the next ( < 0.3 msec), unlike the delay seen with chemical(sometime may be slow) 13 Electrical coupling between mouse hippocampal interneurons. Dual whole-cell patch-clamp recordings performed in brain slices on pairs of fast-spiking interneurons from the dentate gyrus region of the hippocampus have demonstrated that the vast majority of cell pairs are electrically coupled
- 14. (A) Fast-spiking interneurons in the dentate gyrus are identified on the basis of their morphology, location and action potential firing patterns (illustrated here by a representative trace). (B) Electrical coupling between fast- spiking interneurons is reciprocal. (C) Electrical coupling is likely to promote the generation of action potentials. When cell 2 of a pair is injected with subthreshold current pulses, no action potentials are recorded in either cell (left traces). In pairs of electrically coupled interneurons a sub-threshold depolarizing current, however, facilitates the generation of action potentials when concomitant firing is evoked in the second interneuron 14
- 15. Some facts • Electrical communication is not only happens in invertebrate brain where faster transmission is needed to accomplish simple, reactive tasks but also present in vertebrates • It is more abundant in vertebrate CNS. Ex...synchronous oscillatory activity in cortical brain regions and in the dynamic control of retinal circuits. 15
- 16. Gap junctions and connexins between neurons Studies show that the presence of gap junctions and the expression of distinct connexins in different regions (as well as in functions) of the adult mammalian brain, such as the hippocampus, inferior olive,coeruleus, hypothalamus, spinal cord, and olfactory bulb. In situ hybridization, immunocytochemistry, electron microscopy, freeze-fracture immunolabeling,electrophysiology, dye coupling(Are their gap junctions here?), which are ultimately providing a morphological, functional and molecular description of neuronal coupling both in vitro and in vivo. A systematic analysis of freeze-fracture replicas of the rat spinal cord has demonstrated that mixed synapses are relatively abundant between several classes of neurons. 16
- 17. Gap junctions in the developing CNS The electrical coupling actually precedes the establishment of chemical transmission between nerve and muscle cells in culture, hence providing a route for the exchange of signals involved in synapse formation . Thus, at early stages of development it has been proposed that gap junction channels are not only important for electrical synchronization, but are chiefly used as used as a biochemical means that allows neuronal ensembles to exchange small second messenger molecules that shape their activity. It has been noted that the prevalence of gap junctional coupling is well correlated with specific developmental events (including neurulation, cellular and regional differentiation, migration, axon guidance, and the formation of neuronal circuits) and that the basic properties of these channels are well suited to mediate the transfer of developmental signals. 17
- 19. Mouse Brain 19 Connexins are differentially distributed in the mouse brain. The profile of mRNA expression was determined by radioactive in situ hybridization in horizontal brain sections obtained from rats at postnatal day 90. X-ray autoradiograms illustrate the differences between the localization of Cx26, whose transcript is detected only in the meningeal layer (Me) , and Cx43, which is highly expressed in astrocytes . Cx36 mRNA is high in the olfactory bulb (Ob) and also present in other regions, including cortex (Co), hippocampus (Hi) and cerebellum (Cb). Note that the signal for the neuronal Cx36 is absent from white matter structures (arrowhead), such as corpus callosum (Cc), where labeling is evident for Cx32, which is expressed by oligodendrocytes . Scale bar is 2 mm
- 20. • Synchronization of the electrical activity of large populations of neurons;(for example cx36) - e.g., the large populations of neurosecretory neurons that synthesize and release biologically active peptide neurotransmitters and hormones are extensively connected by electrical synapses. - e.g., Synchronization may be required for neuronal development, including the development of chemical synapses. - e.g., Synchronization may be important in functions that require instantaneous responses, such as reflexes and pacemakers. 20
- 21. So In which kind of situation it is good 21
- 22. Electrical signaling and synchronous Oscillatory activity 22 Experiments in mice lacking Cx36 have demonstrated that the disruption of oscillogenesis is observed only in models of gamma frequency, whereas electrical communication within the excitatory neuronal network, as measured using ultrafast population activity Cx36 is involved in gamma frequency (30– 80 Hz), but not ultrafast (150– 200 Hz) oscillations. Extracellular field recordings were obtained in brain slices prepared from wild-type (black traces) and Cx36 knockout (KO) animals (red traces). Cellular assemblies communicating through gap junctions mature during development
- 23. 23
- 24. Future Challenges Electrical Synapse Study 24 • All Connexins roles in the Central nervous system are ambiguous or unknown. • The mechanism by which electrical synapse are regulated are also unknown. • What rule electrical synapse play in brain function and neural basis behaviour.
- 25. Ephaptic Coupling Neurons communicate via specialized molecular machines, the synapses. Such discrete, point-to-point synaptic connectivity, whether chemical or electric, is important for information processing in the brain1–3. However, such integrative processes do not occur in a vacuum Instead, neurons are located in a conductive medium, the extracellular space Neurons Talk Without Synapses 25
- 26. Ephaptic coupling to endogenous electric field activity: why bother? • The idea that the electrical activity generated by nervous tissue may influence the activity of surrounding nervous tissue is one that dates back to the late 19th century.Early experiments, like those by du Bois- Reymond,demonstrated that the firing of a primary nerve may induce the firing of an adjacent secondary nerve (termed "secondary excitation"). This effect was not quantitatively explored, however, until experiments by Katz and Schmitt in 1940, when the two explored the electric interaction of two adjacent limb nerves of the crab Carcinus maenas. 26 In a fruit fly’s antennae, two neighboring neurons can stop each other from firing even if they do not share any direct connections, and help the insect to process smells.This is also ephaptic communication.
- 27. Mechanism and Effects Role in Excitation and Inhibition The early work performed by Katz and Schmitt demonstrated that ephaptic coupling between the two adjacent nerves was insufficient to stimulate an action potential in the resting nerve. Under ideal conditions the maximum depolarization observed was approximately 20% of the threshold stimulus.This effect is the result of the exchange of ions between the two fibers. As the action potential wave propagates along the active axon it draws from ion stores in the resting axon and the characteristic influx and efflux of ions in the action potential are experienced in reverse by the resting axon. The resting axon experiences hyperpolarization, depolarization, and then a smaller hyperpolarization in contrast to the active axon's progression from depolarization to repolarization, and return to resting potential. 27
- 28. Role in Synchronization and Timing In the simpler case of adjacent fibers that experience simultaneous stimulation the impulse is slowed because both fibers are limited to exchange ions solely with the interstitial fluid (increasing the resistance of the nerve). Slightly offset impulses (conduction velocities differing by less than 10%) are able to exchange ions constructively and the action potentials propagate slightly out of phase at the same velocity. 28
- 29. Example Ephaptic coupling in rat Purkinje cells of the cerebellum One of the few known cases of a functional system in which ephaptic coupling is responsible for an observable physiological event is in the Purkinje cells of the rat cerebellum. 29
- 30. how endogenous and externally imposed electric fields impact brain function at different spatial (from synapses to single neurons and neural networks) and temporal scales (from milliseconds to seconds). 30 Rate Hippocampal sliced positioned between parallel plates imposing an extracellular fields.
- 31. Outlook on Ephaptic coupling Advantages 1. it is very fast and has no synaptic delay, and 2. it has very low noise levels. In principle, such communication will occur in any synapse, but its influence will only become significant if the synapse has certain properties. The elements that are crucial for ephaptic neuronal communication are: 1. an ephapse with a large resistance to the extrasynaptic space, 2. a current sink and 3. voltage sensitive channels on the opposing membrane 31
- 32. Conclusion •We cant go for Directly go for In Vivo tests to find out Ephaptic coupling communication details about functional role, does it contribute to neural functions. •There are very less number of evidence to find out which occur very rarely. 32
- 33. References • Hormuzdi a , Mikhail A. Filippova , Georgia Mitropouloub , Hannah Monyer a , Roberto Bruzzonea Electrical synapses: a dynamic signaling system that shapes the activity of neuronal networks Sheriar G. 2003 • http://enhancedwiki.altervista.org/en.php?title=Ephaptic_coupling • https://www.ebi.ac.uk/interpro/entry/IPR002260 • http://www.the-scientist.com/?articles.view/articleNo/33350/title/Neurons-Talk-Without-Synapses/ 33
- 34. Questions ? 34
- 35. ThankYou 35
Editor's Notes
- All of our sensations, feelings, thoughts, motor and emotional responses, learning and memory, the actions of psychoactive drugs, the causes of mental disorders, and any other function or dysfunction of the human brain cannot be understood without the knowledge about the fascinating process of communication between nerve cells (neurons). Neurons must continuously gather information about the internal state of the organism and its external environment, evaluate this information, and coordinate activities appropriate to the situation and to the person's current needs. How neurons process this information? This essentially happens by means of the nerve impulse. A nerve impulse is the transmission of a coded signal from a given stimulus along the membrane of the neuron, starting in the point where it was applied. Nerve impulses can pass from one cell to another, thus creating a chain of information within a network of neurons. http://www.slideshare.net/vacagodx/synaptic-transmission-2474448?next_slideshow=1
- So Basically two main types of communications ..which are widely studied Chemical and electrical and a less known ..communication Ephapting coupling communication.Here mainly I will discuss about Electrical synapse and Ephaptic Coupling.
- This zone of contact presents two distinctive elements, the pre-synaptic terminal and the post-synaptic target site, separated by a synaptic cleft. Pre synaptic cleft from where signal will go Post will receive the signal.
- Since This presentation is specific about only Electrical Synapse,I will discuss and introduce chemical Synapse While Finding Difference Between Them
- In early time neuroscientist thought only one type of synapse is present...So The nature of synaptic transmission was vigorously debated by some of the finest neuroscientists of the last century, who argued either in favor of an electrical mode implying that the action potential in the pre-synaptic neuron induces a passive current flow into the post-synaptic cell, or in favor of a chemical substance, liberated from the pre-synaptic cell upon arrival of an action potential, which interacts with the post-synaptic cell and propagates the stimulus. For some time the strong case made by the unequivocal evidence for chemical transmission in the vertebrate brain and at the neuromuscular junction led to the generalization that all synaptic transmission would be chemical. Then, a direct demonstration of electrical synaptic transmission was first obtained at the giant motor synapse in the crayfish, where it was shown that the post-synaptic response arose in a fraction of a millisecond after pre-synaptic stimulation , and these findings were shortly confirmed in vertebrates and . It is now accepted that either view overestimated just one type of synaptic transmission, as both mechanisms, chemical as well as electrical, co-exist.
- At chemical synapses, an action potential arriving at the pre-synaptic terminal triggers the exocytosis of vesicles filled with neurotransmitters (gray), which are then released in the synaptic cleft. Transmitters diffuse and bind to specific receptors on the post-synaptic cell, where they gate (viz., open or close) ion channels either directly or indirectly, thereby affecting its membrane conductance. In this example, the opening of a ligand-gated channel (green) triggers ionic influx (black) in the post-synaptic cell. (B) At electrical synapses, gap junction channels allow a direct communication between the cytoplasm of the two coupled cells. In
- At chemical synapses, an action potential arriving at the pre-synaptic terminal triggers the exocytosis of vesicles filled with neurotransmitters (gray), which are then released in the synaptic cleft. Transmitters diffuse and bind to specific receptors on the post-synaptic cell, where they gate (viz., open or close) ion channels either directly or indirectly, thereby affecting its membrane conductance. In this example, the opening of a ligand-gated channel (green) triggers ionic influx (black) in the post-synaptic cell. (B) At electrical synapses, gap junction channels allow a direct communication between the cytoplasm of the two coupled cells. In
- Electrical and chemical synapses differ not only in the molecular mechanisms of information transfer, but also in their morphological organization At chemical synapses, there is no continuity between the cytoplasm of the two cells at the synapse, and the distance separating the pre- and post-synaptic membranes, namely the synaptic cleft, is in the order of 20–40 nm. In contrast, electrical synapses are characterized by an area of very close apposition, in the order of 2–4 nm between the pre- and postsynaptic membranes. Within this area of apposition the two cells communicate through gap junctions, cell-to-cell pores that serve as conduits between the cytoplasm of the two cells. The structural proteins comprising these channels, called connexins (Cx), form a multigene family whose members are distinguished according to their predicted molecular mass in kDa (e.g. Cx32, Cx43) .
- Intercellular channels span two plasma membranes and result from the association of two half channels, called connexons, contributed separately by each of the two participating cells. Each connexon, in turn, is a hexameric assembly of connexin subunits. Intercellular channels are defined as homotypic, when the two connexons have the same molecular composition, or heterotypic, when the connexons differ. Connexins have evolved a code of compatibility that permits only selective interactions between connexons, so that the establishment of electrical coupling is also dependent on the pattern of connexin expression between neighboring cells.
- although important differences exist between connexins . Hence, these intercellular channels are also involved in the transmission of metabolic signals between cells, by permitting the passage of second messengers such as inositol trisphosphate (IP3) and cyclic adenosine monophosphate (cAMP)
- Due to their ubiquity and overlapping tissue distributions, it has proved difficult to elucidate the functions of individual connexin isoforms. To circumvent this problem, particular connexin-encoding genes have been subjected to targeted-disruption in mice, and the phenotype of the resulting animals investigated. Around half the connexin isoforms have been investigated in this manner . Further insight into the functional roles of connexins has come from the discovery that a number of human diseases are caused by mutations in connexin genes. For instance, mutations in Cx32 give rise to a form of inherited peripheral neuropathy called X-linked dominant Charcot-Marie-Tooth disease . Similarly, mutations in Cx26 are responsible for both autosomal recessive and dominant forms of nonsyndromic deafness, a disorder characterised by hearing loss, with no apparent effects on other organ systems.
- Voltage responses in cell 1 following depolarizing (upper traces) or hyperpolarizing (lower traces) current injections are reflected in cell 2, albeit with a significant reduction in amplitude.
- A no of report come over the years Freeze-facture immuno
- Neurulation refers to the folding process in vertebrate embryos, which includes the transformation of the neural plate into the neural tube. Neural tube (in an embryo) a hollow structure from which the brain and spinal cord form. Defects in its development can result in congenital abnormalities such as spina bifida.
- In situ hybridization (ISH) is a type of hybridization that uses a labeled complementary DNA, RNA or modified nucleic acids strand (i.e.,probe) to localize a specific DNA or RNA sequence in a portion or section of tissue (in situ), or, if the tissue is small enough (e.g., plant seeds, Drosophila embryos), in the entire tissue (whole mount ISH), in cells, and in circulating tumor cells (CTCs). This is distinct fromimmunohistochemistry, which usually localizes proteins in tissue sections. In situ hybridization is a powerful technique for identifying specific mRNA species within individual cells in tissue sections, providing insights into physiological processes and disease pathogenesis. However, in situ hybridization requires that many steps be taken with precise optimization for each tissue examined and for each probe used. In order to preserve the target mRNA within tissues, it is often required that crosslinking fixatives (such as formaldehyde) be used.
- This is fine Example
- As we already discussed the two best-known types of cell-cell communication are chemical synapses and electrical synapses, which are formed by gap junctions. A third, less well known, form of communication is ephaptic transmission, in which electric fields generated by a specific neuron alter the excitability of neighboring neurons as a result of their anatomical and electrical proximity. The idea that the electrical activity generated by nervous tissue may influence the activity of surrounding nervous tissue is one that dates back to the late 19th century. Early experiments, like those by du Bois-Reymond,demonstrated that the firing of a primary nerve may induce the firing of an adjacent secondary nerve (termed "secondary excitation"). This effect was not quantitatively explored, however, until experiments by Katz and Schmitt in 1940, when the two explored the electric interaction of two adjacent limb nerves of the crab Carcinus maenas. Field effect (Ephaptic)
- Their work demonstrated that the progression of the action potential in the active axon caused excitability changes in the inactive axon. These changes were attributed to the local currents that form the action potential. For example, the currents that caused the depolarization (excitation) of the active nerve caused a corresponding hyperpolarization (depression) of the adjacent resting fiber. Similarly, the currents that caused repolarization of the active nerve caused slight depolarization in the resting fiber. Katz and Schmitt also observed that stimulation of both nerves could cause interference effects. Simultaneous action potential firing caused interference and resulted in decreased conduction velocity, while slightly offset stimulation resulted in synchronization of the two impulses.
- More recent research, however, has focused on the more general case of electric fields that affect a variety of neurons. It has been observed that local field potentials in cortical neurons can serve to synchronize neuronal activity. Although the mechanism is unknown, it is hypothesized that neurons are ephaptically coupled to the frequencies of the local field potential. This coupling may effectively synchronize neurons into periods of enhanced excitability (or depression) and allow for specific patterns of action potential timing (often referred to as spike timing). This effect has been demonstrated and modeled in a variety of cases.
- It was demonstrated in this study that the basket cells which encapsulate some regions of Purkinje fibers can cause inhibitory effects on the Purkinje cells. The firing of these basket cells, which occurs more rapidly than in the Purkinje cells, draws current across the Purkinje cell and generates a passive hyperpolarizing potential which inhibits the activity of the Purkinje cell. Although the exact functional role of this inhibition is still unclear, it may well have a synchronizing effect in the Purkinje cells as the ephaptic effect will limit the firing time.