Heterosynaptic plasticity

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In heterosynaptic plasticity, synaptic pathways that are not specifically stimulated undergo changes (synaptic plasticity) in addition to those who are specifically stimulated. Heterosynaptic Plasticity-1.jpg
In heterosynaptic plasticity, synaptic pathways that are not specifically stimulated undergo changes (synaptic plasticity) in addition to those who are specifically stimulated.

Synaptic plasticity refers to a chemical synapse's ability to undergo changes in strength. [1] Synaptic plasticity is typically input-specific (i. e. homosynaptic plasticity), meaning that the activity in a particular neuron alters the efficacy of a synaptic connection between that neuron and its target. However, in the case of heterosynaptic plasticity, the activity of a particular neuron leads to input unspecific changes in the strength of synaptic connections from other unactivated neurons. [2] [3] A number of distinct forms of heterosynaptic plasticity have been found in a variety of brain regions and organisms. These different forms of heterosynaptic plasticity contribute to a variety of neural processes including associative learning, the development of neural circuits, and homeostasis of synaptic input. [4]

Contents

Homeostatic role

Heterosynaptic plasticity may play an important homeostatic role in neural plasticity by normalizing or limiting the total change of synaptic input during ongoing Hebbian plasticity. [5] Hebbian plasticity, an ubiquitous form of homosynaptic, associative plasticity, is believed to underlie learning and memory. Moreover, Hebbian plasticity is induced by and amplifies correlations in neural circuits which creates a positive feedback loop and renders neural circuits unstable. To avoid this instability Hebbian plasticity needs to be constrained, [6] for instance by the conservation of the total amount of synaptic input. This role is believed to be fulfilled by a diversity of homeostatic mechanisms.

However, to effectively stabilize Hebbian plasticity, which can be induced in a matter of seconds to minutes, homeostatic plasticity has to react rapidly. [7] This requirement, however, is not met by most forms of homeostatic plasticity, which typically act on timescales of hours, days or longer. [8] [9] This limitation does not seem to apply to heterosynaptic plasticity. [10] [11] [12]

To achieve a homeostatic effect, heterosynaptic plasticity serving a homeostatic role have to cause pathway unspecific synaptic changes in the opposite direction as Hebbian plasticity. In other words, whenever homosynaptic long-term potentiation is induced at a given synapse, other unstimulated synapses should be depressed. [2] Conversely, homosynaptic long-term depression would cause other synapses to potentiate in a manner which keeps the average synaptic weight approximately conserved. The scope of these changes could be global or compartmentalized in the dendrites.

Modulatory input-dependent plasticity

In modulatory input-dependent plasticity, Neuron C acts as an interneuron, releasing neuromodulators, which changes synaptic strength between Neuron A and Neuron B. Interneuron-1.jpg
In modulatory input-dependent plasticity, Neuron C acts as an interneuron, releasing neuromodulators, which changes synaptic strength between Neuron A and Neuron B.

One well studied example of heterosynaptic plasticity is modulatory input-dependent plasticity. Modulatory neurons perform neuromodulation, which is the release of neuromodulators. Neuromodulators differ from classical neurotransmitters. Typically, neuromodulators do not directly generate electrical responses in target neurons. Rather, the release of neuromodulators often alters the efficacy of neurotransmission in nearby chemical synapses. Furthermore, the impact of neuromodulators is often quite long lasting in comparison to classical neurotransmitters. [1]

A number of neurotransmitters can act as neuromodulators, particularly biogenic amines such as dopamine and serotonin. [4] These neuromodulators use G-protein coupled receptors which mediate slower modulatory effects and neither hyperpolarize nor depolarize cells. Due to these qualities, GPCR can initiate long-lasting changes in heterosynaptic strength. [1]

The use of these neuromodulators is an example of heterosynaptic plasticity. Released by a neuron called an interneuron, neuromodulators can affect another neuron's efficiency of communication with a postsynaptic cell. Thus, because the interneuron does not specifically activate the postsynaptic neuron (strength in its synaptic plasticity is indirectly affected), this mechanism of modulatory input-dependent plasticity is heterosynaptic. [4] To better understand this process and its vast diversity, key functions of the neuromodulator serotonin in Aplysia californica and dopamine are further illustrated.

Aplysia californica

In Aplysia californica, modulatory interneurons release serotonin, triggering synaptic plasticity in motor neurons. Aplysia-1.jpg
In Aplysia californica, modulatory interneurons release serotonin, triggering synaptic plasticity in motor neurons.

The classic example that demonstrates modulatory input-dependent plasticity involves the marine mollusk, Aplysia californica. Studies in the late 1960s provided the first evidence for plasticity in the chemical synapses of Aplysia. These studies showed that several types of modulatory interneurons were excited in the sensory and motor neuron circuit of Aplysia. In Aplysia, stimulation of the siphon sensory neuron terminals led to an enhanced EPSP in the modulatory interneuron. The modulatory interneurons release serotonin, which triggers synaptic plasticity in motor neurons. [1] Furthermore, when a noxious stimulus was applied to either the head or tail and paired with a light touch to the siphon, it produced a strong motor response, called gill withdrawal reflex. Evidence for long-term plasticity changes was observed several days later when only a light touch to the siphon elicited the same strong response due to a phenomenon called sensitization. These studies show evidence for heterosynaptic strengthening between sensory and motor neurons in Aplysia motor circuitry. [1] [4]

Dopaminergic synapses

Heterosynaptic plasticity is not solely restricted to serotonin. Dopamine has also been shown to act in a neuro modulatory fashion. Much like the serotonin receptors in Aplysia, dopamine receptors are G-protein-coupled receptors that activate cAMP production. This process, however, is important for the storage of memories in mammals, while serotonin's occurs in invertebrates. [4] Within dopaminergic and GABAergic terminals, the neuromodulator dopamine is released via heterosynaptic plasticity. Commonly, this plasticity leads to long-term depression, LTD, mediated by dopamine D1 class receptors. [13] These receptors' activation is required to create LTD and modulate its magnitude. [14] Further research on dopamine's role in neuromodulation is also underway. Experiments performed at the University of Pittsburgh looked at the parallel projects of dopaminergic and GABAergic terminals from the ventral tegmental area to the nucleus accumbens core (NAcCo) in rats. Within these parallel projections, scientists discovered that the release of dopamine heterosynaptically triggers LTD at these synapses. Concluding, dopamine is not just a neuromodulator but can also trigger synaptic plasticity independently in neurons. [13] Therefore, heterosynaptic dopamine signaling in mammals can be best represented by dopamine's biological functions of mediating, as well as independently triggering, changes in synaptic plasticity. [13]

Changes in plasticity during development

Early in development, synaptic connections are not input-specific, most likely because of Ca2+ spillover (i.e. Ca2+ is not restricted to dendrites specifically activated). This spillover represents another mechanism of heterosynaptic change in plasticity. Networks are later refined by input-specific plasticity, which allows for the elimination of connections that are not specifically stimulated. [15] As neuronal circuits mature, it is likely that the concentration of Ca2+ binding proteins increases, which prevents Ca2+ from diffusing to other sites. Increases in localized Ca2+ lead to AMPARs inserted into the membrane. This increase in AMPA density in the postsynaptic membrane increases enables NMDARs to be functional, allowing more Ca2+ to enter the cell. [16] NMDAR subunits also change as neurons mature, increasing the receptor's conductance property. [15] [17] These mechanisms facilitate Ca2+ location restriction, and thus specificity, as an organism progresses through development.

Synaptic Scaling

A neural network that undergoes plastic changes between synapses must initiate normalization mechanisms in order to combat unrestrained potentiation or depression. One mechanism assures that the average firing rate of these neurons is kept at a reasonable rate through synaptic scaling. In this process, input levels are changed in cells to maintain average firing rate. For example, inhibitory synapses are strengthened or excitatory synapses are weakened to normalize the neural network and allow single neurons to regulate their firing rate. [1] Another mechanism is the cell-wide redistribution of synaptic weight. This mechanism conserves the total synaptic weight across the cell by introducing competition between synapses. Thus, normalizing a single neuron after plasticity. [10] During development, cells can be refined when some synapses are preserved and others are discarded to normalize total synaptic weight. In this way, homeostasis is conserved in cells that are undergoing plasticity and normal operation of learning networks is also preserved, allowing new information to be learned. [10]

Related Research Articles

<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">Long-term potentiation</span> Persistent strengthening of synapses based on recent patterns of activity

In neuroscience, long-term potentiation (LTP) is a persistent strengthening of synapses based on recent patterns of activity. These are patterns of synaptic activity that produce a long-lasting increase in signal transmission between two neurons. The opposite of LTP is long-term depression, which produces a long-lasting decrease in synaptic strength.

Hebbian theory is a neuropsychological theory claiming that an increase in synaptic efficacy arises from a presynaptic cell's repeated and persistent stimulation of a postsynaptic cell. It is an attempt to explain synaptic plasticity, the adaptation of brain neurons during the learning process. It was introduced by Donald Hebb in his 1949 book The Organization of Behavior. The theory is also called Hebb's rule, Hebb's postulate, and cell assembly theory. Hebb states it as follows:

Let us assume that the persistence or repetition of a reverberatory activity tends to induce lasting cellular changes that add to its stability. ... When an axon of cell A is near enough to excite a cell B and repeatedly or persistently takes part in firing it, some growth process or metabolic change takes place in one or both cells such that A’s efficiency, as one of the cells firing B, is increased.

In neuroscience, synaptic plasticity is the ability of synapses to strengthen or weaken over time, in response to increases or decreases in their activity. Since memories are postulated to be represented by vastly interconnected neural circuits in the brain, synaptic plasticity is one of the important neurochemical foundations of learning and memory.

In neurophysiology, long-term depression (LTD) is an activity-dependent reduction in the efficacy of neuronal synapses lasting hours or longer following a long patterned stimulus. LTD occurs in many areas of the CNS with varying mechanisms depending upon brain region and developmental progress.

In neuroscience, a silent synapse is an excitatory glutamatergic synapse whose postsynaptic membrane contains NMDA-type glutamate receptors but no AMPA-type glutamate receptors. These synapses are named "silent" because normal AMPA receptor-mediated signaling is not present, rendering the synapse inactive under typical conditions. Silent synapses are typically considered to be immature glutamatergic synapses. As the brain matures, the relative number of silent synapses decreases. However, recent research on hippocampal silent synapses shows that while they may indeed be a developmental landmark in the formation of a synapse, that synapses can be "silenced" by activity, even once they have acquired AMPA receptors. Thus, silence may be a state that synapses can visit many times during their lifetimes.

Spike-timing-dependent plasticity (STDP) is a biological process that adjusts the strength of connections between neurons in the brain. The process adjusts the connection strengths based on the relative timing of a particular neuron's output and input action potentials. The STDP process partially explains the activity-dependent development of nervous systems, especially with regard to long-term potentiation and long-term depression.

<span class="mw-page-title-main">Neural circuit</span> Network or circuit of neurons

A neural circuit is a population of neurons interconnected by synapses to carry out a specific function when activated. Multiple neural circuits interconnect with one another to form large scale brain networks.

Neuromodulation is the physiological process by which a given neuron uses one or more chemicals to regulate diverse populations of neurons. Neuromodulators typically bind to metabotropic, G-protein coupled receptors (GPCRs) to initiate a second messenger signaling cascade that induces a broad, long-lasting signal. This modulation can last for hundreds of milliseconds to several minutes. Some of the effects of neuromodulators include: altering intrinsic firing activity, increasing or decreasing voltage-dependent currents, altering synaptic efficacy, increasing bursting activity and reconfigurating synaptic connectivity.

Metaplasticity is a term originally coined by W.C. Abraham and M.F. Bear to refer to the plasticity of synaptic plasticity. Until that time synaptic plasticity had referred to the plastic nature of individual synapses. However this new form referred to the plasticity of the plasticity itself, thus the term meta-plasticity. The idea is that the synapse's previous history of activity determines its current plasticity. This may play a role in some of the underlying mechanisms thought to be important in memory and learning such as long-term potentiation (LTP), long-term depression (LTD) and so forth. These mechanisms depend on current synaptic "state", as set by ongoing extrinsic influences such as the level of synaptic inhibition, the activity of modulatory afferents such as catecholamines, and the pool of hormones affecting the synapses under study. Recently, it has become clear that the prior history of synaptic activity is an additional variable that influences the synaptic state, and thereby the degree, of LTP or LTD produced by a given experimental protocol. In a sense, then, synaptic plasticity is governed by an activity-dependent plasticity of the synaptic state; such plasticity of synaptic plasticity has been termed metaplasticity. There is little known about metaplasticity, and there is much research currently underway on the subject, despite its difficulty of study, because of its theoretical importance in brain and cognitive science. Most research of this type is done via cultured hippocampus cells or hippocampal slices.

Neural facilitation, also known as paired-pulse facilitation (PPF), is a phenomenon in neuroscience in which postsynaptic potentials (PSPs) evoked by an impulse are increased when that impulse closely follows a prior impulse. PPF is thus a form of short-term synaptic plasticity. The mechanisms underlying neural facilitation are exclusively pre-synaptic; broadly speaking, PPF arises due to increased presynaptic Ca2+
 concentration leading to a greater release of neurotransmitter-containing synaptic vesicles. Neural facilitation may be involved in several neuronal tasks, including simple learning, information processing, and sound-source localization.

<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.

In neuroscience, homeostatic plasticity refers to the capacity of neurons to regulate their own excitability relative to network activity. The term homeostatic plasticity derives from two opposing concepts: 'homeostatic' and plasticity, thus homeostatic plasticity means "staying the same through change". In the nervous system, neurons must be able to evolve with the development of their constantly changing environment while simultaneously staying the same amidst this change. This stability is important for neurons to maintain their activity and functionality to prevent neurons from carcinogenesis. At the same time, neurons need to have flexibility to adapt to changes and make connections to cope with the ever-changing environment of a developing nervous system.

In neuroscience and computer science, synaptic weight refers to the strength or amplitude of a connection between two nodes, corresponding in biology to the amount of influence the firing of one neuron has on another. The term is typically used in artificial and biological neural network research.

Coincidence detection is a neuronal process in which a neural circuit encodes information by detecting the occurrence of temporally close but spatially distributed input signals. Coincidence detectors influence neuronal information processing by reducing temporal jitter and spontaneous activity, allowing the creation of variable associations between separate neural events in memory. The study of coincidence detectors has been crucial in neuroscience with regards to understanding the formation of computational maps in the brain.

<span class="mw-page-title-main">Nonsynaptic plasticity</span> Form of neuroplasticity

Nonsynaptic plasticity is a form of neuroplasticity that involves modification of ion channel function in the axon, dendrites, and cell body that results in specific changes in the integration of excitatory postsynaptic potentials and inhibitory postsynaptic potentials. Nonsynaptic plasticity is a modification of the intrinsic excitability of the neuron. It interacts with synaptic plasticity, but it is considered a separate entity from synaptic plasticity. Intrinsic modification of the electrical properties of neurons plays a role in many aspects of plasticity from homeostatic plasticity to learning and memory itself. Nonsynaptic plasticity affects synaptic integration, subthreshold propagation, spike generation, and other fundamental mechanisms of neurons at the cellular level. These individual neuronal alterations can result in changes in higher brain function, especially learning and memory. However, as an emerging field in neuroscience, much of the knowledge about nonsynaptic plasticity is uncertain and still requires further investigation to better define its role in brain function and behavior.

In neuroscience, synaptic scaling is a form of homeostatic plasticity, in which the brain responds to chronically elevated activity in a neural circuit with negative feedback, allowing individual neurons to reduce their overall action potential firing rate. Where Hebbian plasticity mechanisms modify neural synaptic connections selectively, synaptic scaling normalizes all neural synaptic connections by decreasing the strength of each synapse by the same factor, so that the relative synaptic weighting of each synapse is preserved.

<span class="mw-page-title-main">Synaptic fatigue</span> Form of neural negative feedback

Synaptic fatigue, or short-term synaptic depression, is an activity-dependent form of short term synaptic plasticity that results in the temporary inability of neurons to fire and therefore transmit an input signal. It is thought to be a form of negative feedback in order to physiologically control particular forms of nervous system activity.

Many experiments have been done to find out how the brain interprets stimuli and how animals develop fear responses. The emotion, fear, has been hard-wired into almost every individual, due to its vital role in the survival of the individual. Researchers have found that fear is established unconsciously and that the amygdala is involved with fear conditioning.

<span class="mw-page-title-main">Homosynaptic plasticity</span> Type of synaptic plasticity.

Homosynaptic plasticity is one type of synaptic plasticity. Homosynaptic plasticity is input-specific, meaning changes in synapse strength occur only at post-synaptic targets specifically stimulated by a pre-synaptic target. Therefore, the spread of the signal from the pre-synaptic cell is localized.

References

  1. 1 2 3 4 5 6 Purves, D., Augustine, G.J., Fitzpatrick, D., Hall, W.C., LaMantia, A.S., White, L.E. (2012). Synaptic Plasticity. In Neuroscience (5th ed.) (pp. 163-182). Sunderland, Massachusetts: Sinauer Associates.
  2. 1 2 Lynch, G.S., Dunwiddie, T., and Gribkoff, V. (1977). Heterosynaptic depression: a postsynaptic correlate of long-term potentiation. Nature 266, 737–739.
  3. ↑ Abraham, W.C., and Goddard, G.V. (1983). Asymmetric relationships between homosynaptic long-term potentiation and heterosynaptic long-term depression. Nature 305, 717–719.
  4. 1 2 3 4 5 Bailey, C.H., Giustetto, M., Huang, Y.Y., Hawkins, R.D., Kandel, E.R. (2000) Is heterosynaptic modulation essential for stabilizing Hebbian plasticity and memory. Nature Reviews Neuroscience, 1:1, 11-20.
  5. ↑ Royer, S., and Paré, D. (2003). Conservation of total synaptic weight through balanced synaptic depression and potentiation. Nature 422, 518–522.
  6. ↑ Miller, K.D., and MacKay, D.J. (1994). The role of constraints in Hebbian learning. Neural Comput 6, 100–126.
  7. ↑ Zenke, F., Hennequin, G., and Gerstner, W. (2013). Synaptic Plasticity in Neural Networks Needs Homeostasis with a Fast Rate Detector. PLoS Comput Biol 9, e1003330.
  8. ↑ Turrigiano, G.G., and Nelson, S.B. (2004). Homeostatic plasticity in the developing nervous system. Nat Rev Neurosci 5, 97–107.
  9. ↑ Zenke, F., Gerstner, W., and Ganguli, S. (2017). The temporal paradox of Hebbian learning and homeostatic plasticity. Current Opinion in Neurobiology 43, 166–176.
  10. 1 2 3 Chistiakova, M., Volgushev, M. (2009) Heterosynaptic plasticity in the neocortex. Experimental Brain Research, 199, 377-390.
  11. ↑ Chen, J.-Y., Lonjers, P., Lee, C., Chistiakova, M., Volgushev, M., and Bazhenov, M. (2013). Heterosynaptic Plasticity Prevents Runaway Synaptic Dynamics. J Neurosci 33, 15915–15929.
  12. ↑ Chistiakova, M., Bannon, N.M., Chen, J.-Y., Bazhenov, M., and Volgushev, M. (2015). Homeostatic role of heterosynaptic plasticity: models and experiments. Front Comput Neurosci 9, 89.
  13. 1 2 3 Ishikawa, M., Otaka, M., Huang, Y. H., Neumann, P. A., Winters, B. D., Grace, A. A., Schlüter, O. M., and Dong, Y. (2013). Dopamine Triggers Heterosynaptic Plasticity. The Journal of Neuroscience, 33(16), 6759-6765.
  14. ↑ Sajikumar, S., Frey, J. U. (2004). Late-associativity, Synaptic tagging, and the Role of Dopamine during LTP and LTD. Neurobiology of Learning and Memory, 82 (1), 12-25.
  15. 1 2 Sanes, D.H., Reh, T.A., Harris, W.A. (2012). Synapse Formation and Function, Refinement of Synaptic Connections. In Development of the Nervous System (3rd ed.) (pp. 234-274). Boston, Massachusetts: Elsevier Inc.
  16. ↑ Higley, M.J., Sabatini, B.L. (Feb. 2012.) Calcium Signaling in Dendritic Spines. Cold Spring Harbor Perspectives in Biology. Retrieved from http://cshperspectives.cshlp.org/. doi:10.1101/cshperspect.a005686.
  17. ↑ Tao, H.W.., Zhang, L.I., Engert, F., Poo, M. (Aug. 2001.) Emergence of Input Specificity of LTP during Development of Retinotectal Connections In Vivo. Neuron: 31, 569-580.
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