The term "autapse" was first coined in 1972 by Van der Loos and Glaser, who observed them in Golgi preparations of the rabbit occipital cortex while originally conducting a quantitative analysis of rabbit neocortex circuitry. Also in the 1970s, autapses have been described in dog and rat cerebral cortex, monkey neostriatum, and cat spinal cord.
In 2000, they were first modeled as supporting persistence in recurrent neural networks. In 2004, they were modeled as demonstrating oscillatory behavior, which was absent in the same model neuron without autapse. More specifically, the neuron oscillated between high firing rates and firing suppression, reflecting the spike bursting behavior typically found in cerebral neurons. In 2009, autapses were, for the first time, associated with sustained activation. This proposed a possible function for excitatory autapses within a neural circuit. In 2014, electrical autapses were shown to generate stable target and spiral waves in a neural model network. This indicated that they played a significant role in stimulating and regulating the collective behavior of neurons in the network. In 2016, a model of resonance was offered.
Autapses have been used to simulate "same cell" conditions to help researchers make quantitative comparisons, such as studying how N-methyl-D-aspartate receptor (NMDAR) antagonists affect synaptic versus extrasynaptic NMDARs.
Recently, it has been proposed that autapses could possibly form as a result of neuronal signal transmission blockage, such as in cases of axonal injury induced by poisoning or impeding ion channels. Dendrites from the soma in addition to an auxiliary axon may develop to form an autapse to help remediate the neuron's signal transmission.
Autapses can be either glutamate-releasing (excitatory) or GABA-releasing (inhibitory), just like their traditional synapse counterparts. Similarly, autapses can be electrical or chemical by nature.
Broadly speaking, negative feedback in autapses tends to inhibit excitable neurons whereas positive feedback can stimulate quiescent neurons.
Although the stimulation of inhibitory autapses did not induce hyperpolarizing inhibitory post-synaptic potentials in interneurons of layer V of neocortical slices, they have been shown to impact excitability. Upon using a GABA-antagonist to block autapses, the likelihood of an immediate subsequent second depolarization step increased following a first depolarization step. This suggests that autapses act by suppressing the second of two closely timed depolarization steps and therefore, they may provide feedback inhibition onto these cells. This mechanism may also potentially explain shunting inhibition.
In cell culture, autapses have been shown to contribute to the prolonged activation of B31/B32 neurons, which significantly contribute food-response behavior in Aplysia. This suggests that autapses may play a role in mediating positive feedback. It is important to note that the B31/B32 autapse was unable to play a role in initiating the neuron's activity, although it is believed to have helped sustain the neuron's depolarized state. The extent to which autapses maintain depolarization remains unclear, particularly since other components of the neural circuit (i.e. B63 neurons) are also capable of providing strong synaptic input throughout the depolarization. Additionally, it has been suggested that autapses provide B31/B32 neurons with the ability to quickly repolarize. Bekkers (2009) has proposed that specifically blocking the contribution of autapses and then assessing the differences with or without blocked autapses could better illuminate the function of autapses.
Hindmarsh–Rose (HR) model neurons have demonstrated chaotic, regular spiking, quiescent, and periodic patterns of burst firing without autapses. Upon the introduction of an electrical autapse, the periodic state switches to the chaotic state and displays an alternating behavior that increases in frequency with a greater autaptic intensity and time delay. On the other hand, excitatory chemical autapses enhanced the overall chaotic state. The chaotic state was reduced and suppressed in the neurons with inhibitory chemical autapses. In HR model neurons without autapses, the pattern of firing altered from quiescent to periodic and then to chaotic as DC current was increased. Generally, HR model neurons with autapses have the ability to swap into any firing pattern, regardless of the prior firing pattern.
Autapses have been observed to be relatively more abundant in GABAergic basket and dendrite-targeting cells of the cat visual cortex compared to spiny stellate, double bouquet, and pyramidal cells, suggesting that the degree of neuron self-innervation is cell-specific. Additionally, dendrite-targeting cell autapses were, on average, further from the soma compared to basket cell autapses.
80% of layer V pyramidal neurons in developing rat neocortices contained autaptic connections, which were located more so on basal dendrites and apical oblique dendrites rather than main apical dendrites. The dendritic positions of synaptic connections of the same cell type were similar to those of autapses, suggesting that autaptic and synaptic networks share a common mechanism of formation.
In the 1990s, paroxysmal depolarizing shift-type interictal epileptiform discharges has been suggested to be primarily dependent on autaptic activity for solitary excitatory hippocampal rat neurons grown in microculture.
More recently, in human neocortical tissues of patients with intractable epilepsy, the GABAergic output autapses of fast-spiking (FS) neurons have been shown to have stronger asynchronous release (AR) compared to both non-epileptic tissue and other types of synapses involving FS neurons. The study found similar results using a rat model as well. An increase in residual Ca2+ concentration in addition to the action potential amplitude in FS neurons was suggested to cause this increase in AR of epileptic tissue. Anti-epileptic drugs could potentially target this AR of GABA that seems to rampantly occur at FS neuron autapses.
Using a glia-conditioned medium to treat glia-free purified rat retinal ganglion microcultures has been shown to significantly increase the number of autapses per neuron compared to a control. This suggests that glia-derived soluble, proteinase K-sensitive factors induce autapse formation in rat retinal ganglion cells.
An axon (from Greek ἄξων áxōn, axis), or nerve fiber, is a long, slender projection of a nerve cell, or neuron, in vertebrates, that typically conducts electrical impulses known as action potentials away from the nerve cell body. The function of the axon is to transmit information to different neurons, muscles, and glands. In certain sensory neurons (pseudounipolar neurons), such as those for touch and warmth, the axons are called afferent nerve fibers and the electrical impulse travels along these from the periphery to the cell body, and from the cell body to the spinal cord along another branch of the same axon. Axon dysfunction has caused many inherited and acquired neurological disorders which can affect both the peripheral and central neurons. Nerve fibers are classed into three types – group A nerve fibers, group B nerve fibers, and group C nerve fibers. Groups A and B are myelinated, and group C are unmyelinated. These groups include both sensory fibers and motor fibers. Another classification groups only the sensory fibers as Type I, Type II, Type III, and Type IV.
An axon is one of two types of cytoplasmic protrusions from the cell body of a neuron; the other type is a dendrite. Axons are distinguished from dendrites by several features, including shape (dendrites often taper while axons usually maintain a constant radius), length (dendrites are restricted to a small region around the cell body while axons can be much longer), and function (dendrites receive signals whereas axons transmit them). Some types of neurons have no axon and transmit signals from their dendrites. In some species, axons can emanate from dendrites and these are known as axon-carrying dendrites. No neuron ever has more than one axon; however in invertebrates such as insects or leeches the axon sometimes consists of several regions that function more or less independently of each other.Axons are covered by a membrane known as an axolemma; the cytoplasm of an axon is called axoplasm. Most axons branch, in some cases very profusely. The end branches of an axon are called telodendria. The swollen end of a telodendron is known as the axon terminal which joins the dendron or cell body of another neuron forming a synaptic connection. Axons make contact with other cells—usually other neurons but sometimes muscle or gland cells—at junctions called synapses. In some circumstances, the axon of one neuron may form a synapse with the dendrites of the same neuron, resulting in an autapse. At a synapse, the membrane of the axon closely adjoins the membrane of the target cell, and special molecular structures serve to transmit electrical or electrochemical signals across the gap. Some synaptic junctions appear along the length of an axon as it extends—these are called en passant ("in passing") synapses and can be in the hundreds or even the thousands along one axon. Other synapses appear as terminals at the ends of axonal branches.
A single axon, with all its branches taken together, can innervate multiple parts of the brain and generate thousands of synaptic terminals. A bundle of axons make a nerve tract in the central nervous system, and a fascicle in the peripheral nervous system. In placental mammals the largest white matter tract in the brain is the corpus callosum, formed of some 20 million axons in the human brain.Chemical synapse
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.
At a chemical synapse, one neuron releases neurotransmitter molecules into a small space (the synaptic cleft) that is adjacent to another neuron. The neurotransmitters are contained within small sacs called synaptic vesicles, and are released into the synaptic cleft by exocytosis. These molecules then bind to neurotransmitter receptors on the postsynaptic cell. Finally, the neurotransmitters are cleared from the synapse through one of several potential mechanisms including enzymatic degradation or re-uptake by specific transporters either on the presynaptic cell or on some other neuroglia to terminate the action of the neurotransmitter.
The adult human brain is estimated to contain from 1014 to 5 × 1014 (100–500 trillion) synapses. Every cubic millimeter of cerebral cortex contains roughly a billion (short scale, i.e. 109) of them. The number of synapses in the human cerebral cortex has separately been estimated at 0.15 quadrillion (150 trillion)The word "synapse" comes from "synaptein", which Sir Charles Scott Sherrington and colleagues coined from the Greek "syn-" ("together") and "haptein" ("to clasp"). Chemical synapses are not the only type of biological synapse: electrical and immunological synapses also exist. Without a qualifier, however, "synapse" commonly means chemical synapse.Dendrite
Dendrites (from Greek δένδρον déndron, "tree"), also dendrons, are branched protoplasmic extensions of a nerve cell that propagate the electrochemical stimulation received from other neural cells to the cell body, or soma, of the neuron from which the dendrites project. Electrical stimulation is transmitted onto dendrites by upstream neurons (usually via their axons) via synapses which are located at various points throughout the dendritic tree. Dendrites play a critical role in integrating these synaptic inputs and in determining the extent to which action potentials are produced by the neuron. Dendritic arborization, also known as dendritic branching, is a multi-step biological process by which neurons form new dendritic trees and branches to create new synapses. The morphology of dendrites such as branch density and grouping patterns are highly correlated to the function of the neuron. Malformation of dendrites is also tightly correlated to impaired nervous system function. Some disorders that are associated with the malformation of dendrites are autism, depression, schizophrenia, Down syndrome and anxiety.
Certain classes of dendrites contain small projections referred to as dendritic spines that increase receptive properties of dendrites to isolate signal specificity. Increased neural activity and the establishment of long-term potentiation at dendritic spines change the size, shape, and conduction. This ability for dendritic growth is thought to play a role in learning and memory formation. There can be as many as 15,000 spines per cell, each of which serves as a postsynaptic process for individual presynaptic axons. Dendritic branching can be extensive and in some cases is sufficient to receive as many as 100,000 inputs to a single neuron.Dendrites are one of two types of protoplasmic protrusions that extrude from the cell body of a neuron, the other type being an axon. Axons can be distinguished from dendrites by several features including shape, length, and function. Dendrites often taper off in shape and are shorter, while axons tend to maintain a constant radius and be relatively long. Typically, axons transmit electrochemical signals and dendrites receive the electrochemical signals, although some types of neurons in certain species lack axons and simply transmit signals via their dendrites. Dendrites provide an enlarged surface area to receive signals from the terminal buttons of other axons, and the axon also commonly divides at its far end into many branches (telodendria) each of which ends in a nerve terminal, allowing a chemical signal to pass simultaneously to many target cells. Typically, when an electrochemical signal stimulates a neuron, it occurs at a dendrite and causes changes in the electrical potential across the neuron's plasma membrane. This change in the membrane potential will passively spread across the dendrite but becomes weaker with distance without an action potential. An action potential propagates the electrical activity along the membrane of the neuron's dendrites to the cell body and then afferently down the length of the axon to the axon terminal, where it triggers the release of neurotransmitters into the synaptic cleft. However, synapses involving dendrites can also be axodendritic, involving an axon signaling to a dendrite, or dendrodendritic, involving signaling between dendrites. An autapse is a synapse in which the axon of one neuron transmits signals to its own dendrites.
There are three main types of neurons; multipolar, bipolar, and unipolar. Multipolar neurons, such as the one shown in the image, are composed of one axon and many dendritic trees. Pyramidal cells are multipolar cortical neurons with pyramid shaped cell bodies and large dendrites called apical dendrites that extend to the surface of the cortex. Bipolar neurons have one axon and one dendritic tree at opposing ends of the cell body. Unipolar neurons have a stalk that extends from the cell body that separates into two branches with one containing the dendrites and the other with the terminal buttons. Unipolar dendrites are used to detect sensory stimuli such as touch or temperature. other parts of a neuron also include an axonElectrical 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. At gap junctions, such cells approach within about 3.8 nm of each other, a much shorter distance than the 20- to 40-nanometer distance that separates cells at chemical synapse. In many animals, electrical synapse-based systems co-exist with chemical synapses.
Compared to chemical synapses, electrical synapses conduct nerve impulses faster, but, unlike chemical synapses, they lack gain—the signal in the postsynaptic neuron is the same or smaller than that of the originating neuron. The fundamental bases for perceiving electrical synapses comes down to the connexons that are located in the gap junction between two neurons. Electrical synapses are often found in neural systems that require the fastest possible response, such as defensive reflexes. An important characteristic of electrical synapses is that they are mostly bidirectional (allow impulse transmission in either direction).Ganglion
A ganglion is a nerve cell cluster or a group of nerve cell bodies located in the autonomic nervous system and sensory system. Ganglia house the cell bodies of afferent nerves (input nerve fibers) and efferent nerves (output/motor nerve fibers), or axons.
A pseudoganglion looks like a ganglion, but only has nerve fibers and has no nerve cell bodies.Neuron
A neuron, also known as a neurone (British spelling) or nerve cell, is an electrically excitable cell that communicates with other cells via specialized connections called synapses. It is the main component of nervous tissue. All animals except sponges and placozoans have neurons, but other multicellular organisms such as plants do not.
Neurons are typically classified into three types based on their function. Sensory neurons respond to stimuli such as touch, sound, or light that affect the cells of the sensory organs, and they send signals to the spinal cord or brain. Motor neurons receive signals from the brain and spinal cord to control everything from muscle contractions to glandular output. Interneurons connect neurons to other neurons within the same region of the brain or spinal cord. A group of connected neurons is called a neural circuit.
A typical neuron consists of a cell body (soma), dendrites, and a single axon. The soma is usually compact. The axon and dendrites are filaments that extrude from it. Dendrites typically branch profusely and extend a few hundred micrometers from the soma. The axon leaves the soma at a swelling called the axon hillock, and travels for as far as 1 meter in humans or more in other species. It branches but usually maintains a constant diameter. At the farthest tip of the axon's branches are axon terminals, where the neuron can transmit a signal across the synapse to another cell. Neurons may lack dendrites or have no axon. The term neurite is used to describe either a dendrite or an axon, particularly when the cell is undifferentiated.
Most neurons receive signals via the dendrites and soma and send out signals down the axon. At the majority of synapses, signals cross from the axon of one neuron to a dendrite of another. However, synapses can connect an axon to another axon or a dendrite to another dendrite.
The signaling process is partly electrical and partly chemical. Neurons are electrically excitable, due to maintenance of voltage gradients across their membranes. If the voltage changes by a large enough amount over a short interval, the neuron generates an all-or-nothing electrochemical pulse called an action potential. This potential travels rapidly along the axon, and activates synaptic connections as it reaches them. Synaptic signals may be excitatory or inhibitory, increasing or reducing the net voltage that reaches the soma.
In most cases, neurons are generated by neural stem cells during brain development and childhood. Neurogenesis largely ceases during adulthood in most areas of the brain. However, strong evidence supports generation of substantial numbers of new neurons in the hippocampus and olfactory bulb.Synapse
In the nervous system, a synapse is a structure that permits a neuron (or nerve cell) to pass an electrical or chemical signal to another neuron or to the target effector cell.
Santiago Ramón y Cajal proposed that neurons are not continuous throughout the body, yet still communicate with each other, an idea known as the neuron doctrine. The word "synapse" – from the Greek synapsis (συνάψις), meaning "conjunction", in turn from συνάπτεὶν (συν ("together") and ἅπτειν ("to fasten")) – was introduced in 1897 by the English neurophysiologist Charles Sherrington in Michael Foster's Textbook of Physiology. Sherrington struggled to find a good term that emphasized a union between two separate elements, and the actual term "synapse" was suggested by the English classical scholar Arthur Woollgar Verrall, a friend of Foster. Some authors generalize the concept of the synapse to include the communication from a neuron to any other cell type, such as to a motor cell, although such non-neuronal contacts may be referred to as junctions (a historically older term).
Synapses are essential to neuronal function: neurons are cells that are specialized to pass signals to individual target cells, and synapses are the means by which they do so. At a synapse, the plasma membrane of the signal-passing neuron (the presynaptic neuron) comes into close apposition with the membrane of the target (postsynaptic) cell. Both the presynaptic and postsynaptic sites contain extensive arrays of a molecular machinery that link the two membranes together and carry out the signaling process. In many synapses, the presynaptic part is located on an axon and the postsynaptic part is located on a dendrite or soma. Astrocytes also exchange information with the synaptic neurons, responding to synaptic activity and, in turn, regulating neurotransmission. Synapses (at least chemical synapses) are stabilized in position by synaptic adhesion molecules (SAMs) projecting from both the pre- and post-synaptic neuron and sticking together where they overlap; SAMs may also assist in the generation and functioning of synapses.