Activity-dependent plasticity
Encyclopedia
A defining feature of the brain is its capacity to undergo changes based on activity-dependent functions, also called activity-dependent plasticity. Its ability to remodel itself forms the basis of the brain’s capacity to retain memories, improve motor function, and enhance comprehension and speech amongst other things. It is this trait to retain and form memories that is functionally linked to plasticity
and therefore many of the functions individuals perform on a daily basis. This plasticity is the result of changed gene expression that occurs because of organized cellular mechanisms.
The brain’s ability to adapt toward active functions has allowed humans to specialize in specific processes based on relative use and activity. For example, a right-handed person may perform any movement poorly with his/her left hand but continuous practice with the less dominant hand can make both hands just as able. Another example is if someone was born with a neurological disorder
such as autism
or had a stroke
that resulted in a disorder, then they are capable of retrieving much of their lost function by practicing and “rewiring” the brain in order to incorporate these lost manners. Thanks to the pioneers within this field, many of these advances have become available to most people and many more will continue to arrive as new features of plasticity are discovered.
. It was believed that each region of the brain
had a set and specific function. Despite closed-mindedness and ignorance, several pioneers pushed the idea of plasticity through means of various experiments and research. There are others that helped to the current progress of activity-dependent plasticity but the following contributed very effective results and ideas early on.
Another pioneer within the field of activity-dependent plasticity is Michael Merzenich
, currently a professor in neuroscience at the University of California, San Francisco. He is considered an expert on brain plasticity and has a long list of achievements and contributions toward the field. One of his contributions includes mapping out and documenting the reorganization of cortical regions after alterations due to plasticity
. While assessing the recorded changes in the primary somatosensory cortex of adult monkeys, he looked at several features of the data including how altered schedules of activity from the skin remap to cortical modeling and other factors that affect the representational remodeling of the brain. His findings within these studies have since been applied to youth development and children with language-based learning impairments. Through many studies involving adaptive training exercises on computer, he has successfully designed methods to improve their temporal processing skills. These adaptive measures include word-processing games and comprehension tests that involve multiple regions of the brain in order to answer. The results later translated into his development of the Fast Forword
program in 1996, which aims to enhance cognitive skills of children between kindergarten and twelfth grade by focusing on developing “phonological awareness.” It has proven very successful at helping children with a variety of cognitive complications. In addition, it has led to in depth studies of specific complications such as autism
and retardation
and the causes of them. Alongside a team of scientists, Merzenich helped to provide evidence that autism probes monochannel perception where a stronger stimulus-driven representation dominates behavior and weaker stimuli are practically ignored in comparison.
Neuron
s are the basic functional unit of the brain and process and transmit information through signals. Many different types of neurons exist, such as sensory neurons, motor neurons, inter neurons, and sound neurons. Each respond to specific stimuli and send respective and appropriate chemical signals to other regions to distribute the information. The basic structure of a neuron is shown here on the right and consists of a nucleus
that contains genetic information; the cell body, or the soma
, that has dendritic branches that receive information; a long, thin axon
that extends to the axon terminal
; and an axon terminal where branching dendrites send information. The dendrites give and receive information through a small gap called a synapse
. This component of the neuron contains a variety of chemical messengers and proteins that allow for the transmission of information. It is the variety of proteins and affect of the signal that fundamentally lead to the plasticity
feature.
More important than structures and regions are the subunits involved in these changes: AMPA
and NMDA
receptors are capable of altering long and short-term potentiation between neurons. NMDA receptors can detect local activity due to activation and therefore modify signaling in the post-synaptic cell. The increased activity and coordination between pre- and post-synaptic receptors leads to more permanent changes and therefore result in changes in plasticity. Hebb’s postulate addresses this fact by stating that synaptic terminals are strengthened by correlated activity and will therefore sprout new branches. However, terminals that experience weakened and minimal activity will eventually lose their synaptic connection and deteriorate.
A major target of all molecular signaling is the inhibitory connections made by GABA
ergic neurons. These receptors exist at postsynaptic sites and along with the regulation of local inhibitory synapses have been found to be very sensitive to critical period alterations. Any alteration to the receptors leads to changed concentrations of calcium
in the affected cells and can ultimately influence dendritic and axonal branching. This concentration change is the result of many kinase
s being activated, the byproduct of which may enhance specific gene expression.
In addition, it has been identified that the wg postsynaptic pathway, which is responsible for the coding and production of many molecules for development events, can be bidirectionally stimulated and is responsible for the downstream alteration of the postsynaptic neuron. When the wg presynaptic pathway is activated, however, it alters cytoskeletal structure through transcription and translation.
Cell adhesion molecules (CAMs) are also important in plasticity as they help coordinate the signaling across the synapse. More specifically, integrins, which are receptors for extracellular matrix proteins and involved with CAMs, are explicitly incorporated in synapse maturation and memory formation. They play a crucial role in the feedback regulation of excitatory synaptic strength, or long-term potentiation
(LTP), and help to control synaptic strength by regulating AMPA
receptors, which result in quick, short synaptic currents. But, it is the metabotropic glutamate receptor 1 (mGlu1) that has been discovered to be required for activity-dependent synaptic plasticity in associative learning.
Activity-dependent plasticity is even seen in the primary visual cortex, a region of the brain that processes visual stimuli and is capable of modifying the experienced stimuli based on active sensing and arousal states. It is known that synaptic communication trends between excited and depressed states relative to the light/dark cycle. By experimentation on Long Evans rats, it was found that visual experience during vigilant states leads to increased responsiveness and plastic changes in the visual cortex. More so, depressed states were found to negatively alter the stimulus so the reaction was not as energetic. This experiment proves that even the visual cortex is capable of achieving activity-dependent plasticity as it is reliant on both visual exploration and the arousal state of the animal.
s that provide the basis for synaptic plasticity connected to learning
and memory
. Dendritic spines accomplish this by transforming synaptic input into neuronal output and also by helping to define the relationship between synapses.
In recent studies, a specific gene has also been identified as having a strong role in synapse growth and activity-dependent plasticity: the microRNA 132 gene (miR132). This gene is regulated by the cAMP response element-binding (CREB) protein pathway and is capable of enhancing dendritic growth when activated. The miR132 gene is another component that is responsible for the brain’s plasticity and helps to establish stronger connections between neurons.
Another plasticity-related gene involved in learning and memory is Arc/Arg3.1. The Arc gene is activity-regulated and the transcribed mRNA is localized to activated synaptic sites where the translated protein plays a role in AMPA receptor trafficking. Arc is a member of a class of proteins called immediate early genes that are rapidly transcribed in response to synaptic input. Of the estimated 30-40 genes that comprise the total neuronal IEG response, all are prototypical activity-dependent genes and a number have been implicated in learning and memory. For example, zif268
, Arc
, beta-activin, tPA
, Homer, and COX-2 have all been implicated in long-term potentiation
(LTP), a cellular correlate of learning and memory.
(LTD), synaptic elimination, neurogenesis
, and synaptogenesis
. The mechanisms of activity-dependent plasticity result in membrane depolarization and calcium
influx, which in turn trigger cellular changes that affect synaptic connections and gene transcription
. In essence, neuronal activity helps to regulate gene expression
for dendritic branching and synapse development while mutation
s in activity-dependent transcription-related genes can lead to neurological disorders. Each of the studies’ findings aims to help proper development of the brain while improving a wide variety of tasks such as speech, movement, comprehension, and memory. More so, the findings better explain the development induced by plasticity.
It is known that during postnatal life a critical step to nervous system development is synapse elimination. The changes in synaptic connections and strength are results from LTP and LTD and are strongly regulated by the release of brain-derived neurotrophic factor
(BDNF), an activity-dependent synapse-development protein. In addition to BDNF, Nogo-66 receptors, and more specifically NgR1, are also involved in the development and regulation of neuronal structure. Damage to this receptor leads to pointless LTP and attenuation of LTD. Both situations imply that NgR1 is a regulator of synaptic plasticity. From experiments, it has been found that stimulation inducing LTD leads to a reduction in synaptic strength and loss of connections but, when coupled simultaneously with low-frequency stimulation, helps the restructuring of synaptic contacts. The implications of this finding include helping people with receptor damage and providing insight into the mechanism behind LTP.
Another mechanism that gives rise to activity-dependent plasticity includes the excitatory corticostriatal pathway that allows for the storage of adaptive motor behaviors. This pathway is also capable of adhering to long-lasting synaptic changes. The change in synaptic strength is responsible for motor learning and is dependent on the simultaneous activation of glutamatergic corticostriatal and dopaminergic nigrostriatal pathways. These are the very pathways that are affected in Parkinson's disease
and the degeneration of synapses within this disorder may be responsible for the loss of cognitive abilities. Therefore, the impairment of DA/ACh-dependent learning can lead to the storage of inessential memories.
. The two types of mental retardation related to plasticity depend on dysfunctional neuronal development or alterations in molecular mechanisms involved in synaptic organization. Complications within either of these types can greatly reduce brain function and more importantly brain capability and comprehension
.
that left the 65-year-old man half-paralyzed and unable to speak. After one year of crawling and unusual therapy tactics including playing basic children’s games and washing pots, his father’s rehabilitation was nearly complete and he went back to his role as a professor at City College in New York. The remarkable recovery from a stroke proves that even someone with abnormal behavior and severe medical complications can recover nearly all of the normal functions by much practice and perseverance: thus the message behind activity-dependent plasticity.
Recent studies have reported that a specific gene, FMR1, is highly involved in activity-dependent plasticity and Fragile X syndrome (FraX) is the result of this gene’s loss of function. FMR1 produces FMRP, which mediates activity-dependent control of synaptic structure. The loss or absence of this gene almost certainly leads to both autism
and mental retardation
. Dr. Gatto has found that early introduction of the product FMRP results in nearly complete restructuring of the synapses. This method is not as effective, though, when introduced into a mature subject and only partially accommodates for the losses of FMR1. The discovery of this gene provides a possible location for intervention for young children with these abnormalities as this gene and its product act early to construct synaptic architecture.
, and adaptation is the result of LTP and LTD, two activity-dependent plasticity mechanisms that stress can directly suppress. Several experiments have been conducted in order to discover the specific mechanisms for this suppression and also possible intervention methods. Dr. Li and several others have actually identified the TRPV1 channel as a target to facilitate LTP and suppress LTD, therefore helping to protect the feature of synaptic plasticity and retention of memory from the effects of stress.
, Parkinson’s Disease, stress, and stroke
victims. In addition to a better understanding of the various disorders, neurologists should and will look at the plasticity incurred by the immune system
, as it will provide great insight into diseases and also give the basis of new immune-centered therapeutics. A better perspective of the cellular mechanisms that regulate neuronal morphology is the next step to discovering new treatments for learning and memory pathological conditions.
Plasticity
Plasticity may refer to:Science* Plasticity , in physics and engineering, plasticity is the propensity of a material to undergo permanent deformation under load...
and therefore many of the functions individuals perform on a daily basis. This plasticity is the result of changed gene expression that occurs because of organized cellular mechanisms.
The brain’s ability to adapt toward active functions has allowed humans to specialize in specific processes based on relative use and activity. For example, a right-handed person may perform any movement poorly with his/her left hand but continuous practice with the less dominant hand can make both hands just as able. Another example is if someone was born with a neurological disorder
Neurological disorder
A neurological disorder is a disorder of the body's nervous system. Structural, biochemical or electrical abnormalities in the brain, spinal cord, or in the nerves leading to or from them, can result in symptoms such as paralysis, muscle weakness, poor coordination, loss of sensation, seizures,...
such as autism
Autism
Autism is a disorder of neural development characterized by impaired social interaction and communication, and by restricted and repetitive behavior. These signs all begin before a child is three years old. Autism affects information processing in the brain by altering how nerve cells and their...
or had a stroke
Stroke
A stroke, previously known medically as a cerebrovascular accident , is the rapidly developing loss of brain function due to disturbance in the blood supply to the brain. This can be due to ischemia caused by blockage , or a hemorrhage...
that resulted in a disorder, then they are capable of retrieving much of their lost function by practicing and “rewiring” the brain in order to incorporate these lost manners. Thanks to the pioneers within this field, many of these advances have become available to most people and many more will continue to arrive as new features of plasticity are discovered.
History
During the first half of the 1900s, the word ‘plasticity’ was considered foul and directly and indirectly rejected throughout science. Many scientists found it hard to receive funding because nearly everyone unanimously supported the fact that the brain was fully developed at adulthood and specific regions were unable to change functions after the critical periodCritical period
This article is about a critical period in an organism's or person's development. See also America's Critical Period.In general, a critical period is a limited time in which an event can occur, usually to result in some kind of transformation...
. It was believed that each region of the brain
Brain
The brain is the center of the nervous system in all vertebrate and most invertebrate animals—only a few primitive invertebrates such as sponges, jellyfish, sea squirts and starfishes do not have one. It is located in the head, usually close to primary sensory apparatus such as vision, hearing,...
had a set and specific function. Despite closed-mindedness and ignorance, several pioneers pushed the idea of plasticity through means of various experiments and research. There are others that helped to the current progress of activity-dependent plasticity but the following contributed very effective results and ideas early on.
Pioneers of activity-dependent plasticity
The history of activity-dependent plasticity begins with Paul Bach y Rita. With conventional ideology being that the brain development is finalized upon adulthood, Bach y Rita designed several experiments in the late 1960s and 1970s that proved that the brain is capable of changing. These included a pivotal visual substitution method for blind people provided by tactile image projection in 1969. The basis behind this experiment was to take one sense and use it to detect another: in this case use the sense of touch on the tongue to visualize the surrounding. This experiment was years ahead of its time and lead to many questions and applications. A similar experiment was reported again by Bach y Rita in 1986 where vibrotactile stimulation were delivered to the index fingertips of naive blindfolded subjects. Even though the experiment did not yield great results, it supported the study and proposed further investigations. In 1998, his design was even further developed and tested again with a 49-point electrotactile stimulus array on the tongue. He found that five sighted adult subjects recognized shapes across all sizes 79.8% of the time, a remarkable finding that has led to the incorporation of the tongue electrotactile stimulus into cosmetically acceptable and practical designs for blind people. In later years, he has published a number of other articles including “Seeing with the brain” in 2003 where Bach y Rita addresses the plasticity of the brain relative to visual learning. Here, images are enhanced and perceived by other plastic mechanisms within the realm of information passing to the brain.Another pioneer within the field of activity-dependent plasticity is Michael Merzenich
Michael Merzenich
Michael M. Merzenich is a professor emeritus neuroscientist at the University of California, San Francisco. His contributions to the field are numerous. He took the sensory cortex maps developed by his predecessors like Archie Tunturi, Clinton Woolsey, Vernon Mountcastle, Wade Marshall, and Philip...
, currently a professor in neuroscience at the University of California, San Francisco. He is considered an expert on brain plasticity and has a long list of achievements and contributions toward the field. One of his contributions includes mapping out and documenting the reorganization of cortical regions after alterations due to plasticity
Plasticity
Plasticity may refer to:Science* Plasticity , in physics and engineering, plasticity is the propensity of a material to undergo permanent deformation under load...
. While assessing the recorded changes in the primary somatosensory cortex of adult monkeys, he looked at several features of the data including how altered schedules of activity from the skin remap to cortical modeling and other factors that affect the representational remodeling of the brain. His findings within these studies have since been applied to youth development and children with language-based learning impairments. Through many studies involving adaptive training exercises on computer, he has successfully designed methods to improve their temporal processing skills. These adaptive measures include word-processing games and comprehension tests that involve multiple regions of the brain in order to answer. The results later translated into his development of the Fast Forword
Fast ForWord
Fast ForWord is a family of educational software products intended to enhance cognitive skills of children, especially focused on developing "phonological awareness" . It is marketed as a therapy for strengthening the skills of memory, attention, processing rate, and sequencing for children...
program in 1996, which aims to enhance cognitive skills of children between kindergarten and twelfth grade by focusing on developing “phonological awareness.” It has proven very successful at helping children with a variety of cognitive complications. In addition, it has led to in depth studies of specific complications such as autism
Autism
Autism is a disorder of neural development characterized by impaired social interaction and communication, and by restricted and repetitive behavior. These signs all begin before a child is three years old. Autism affects information processing in the brain by altering how nerve cells and their...
and retardation
Retardation
Retardation is the act or result of delaying; the extent to which anything is retarded or delayed; that which retards or delays. In particular, it can mean:-In engineering:* Negative acceleration in mechanics Retardation is the act or result of delaying; the extent to which anything is retarded...
and the causes of them. Alongside a team of scientists, Merzenich helped to provide evidence that autism probes monochannel perception where a stronger stimulus-driven representation dominates behavior and weaker stimuli are practically ignored in comparison.
Structure of neuron
Neuron
A neuron is an electrically excitable cell that processes and transmits information by electrical and chemical signaling. Chemical signaling occurs via synapses, specialized connections with other cells. Neurons connect to each other to form networks. Neurons are the core components of the nervous...
s are the basic functional unit of the brain and process and transmit information through signals. Many different types of neurons exist, such as sensory neurons, motor neurons, inter neurons, and sound neurons. Each respond to specific stimuli and send respective and appropriate chemical signals to other regions to distribute the information. The basic structure of a neuron is shown here on the right and consists of a nucleus
Cell nucleus
In cell biology, the nucleus is a membrane-enclosed organelle found in eukaryotic cells. It contains most of the cell's genetic material, organized as multiple long linear DNA molecules in complex with a large variety of proteins, such as histones, to form chromosomes. The genes within these...
that contains genetic information; the cell body, or the soma
Soma
Soma , or Haoma , from Proto-Indo-Iranian *sauma-, was a ritual drink of importance among the early Indo-Iranians, and the subsequent Vedic and greater Persian cultures. It is frequently mentioned in the Rigveda, whose Soma Mandala contains 114 hymns, many praising its energizing qualities...
, that has dendritic branches that receive information; a long, thin axon
Axon
An axon is a long, slender projection of a nerve cell, or neuron, that conducts electrical impulses away from the neuron's cell body or soma....
that extends to the axon terminal
Axon terminal
Axon terminals are distal terminations of the branches of an axon. An axon nerve fiber is a long, slender projection of a nerve cell, or neuron, that conducts electrical impulses away from the neuron's cell body, or soma, in order to transmit those impulses to other neurons.Neurons are...
; and an axon terminal where branching dendrites send information. The dendrites give and receive information through a small gap called a synapse
Synapse
In the nervous system, a synapse is a structure that permits a neuron to pass an electrical or chemical signal to another cell...
. This component of the neuron contains a variety of chemical messengers and proteins that allow for the transmission of information. It is the variety of proteins and affect of the signal that fundamentally lead to the plasticity
Plasticity
Plasticity may refer to:Science* Plasticity , in physics and engineering, plasticity is the propensity of a material to undergo permanent deformation under load...
feature.
Structures and pathways involved
Nearly every cortex and region within the brain is involved in its plasticity feature since most regions are capable of adopting other regions’ functions based on relative use and the “rewiring” of the topographic map. The reorganization of sensory and motor maps involves a variety of pathways and cellular structures related to relative activity.More important than structures and regions are the subunits involved in these changes: AMPA
AMPA
AMPA is a compound that is a specific agonist for the AMPA receptor, where it mimics the effects of the neurotransmitter glutamate....
and NMDA
NMDA
N-Methyl-D-aspartic acid or N-Methyl-D-aspartate is an amino acid derivative which acts as a specific agonist at the NMDA receptor mimicking the action of glutamate, the neurotransmitter which normally acts at that receptor...
receptors are capable of altering long and short-term potentiation between neurons. NMDA receptors can detect local activity due to activation and therefore modify signaling in the post-synaptic cell. The increased activity and coordination between pre- and post-synaptic receptors leads to more permanent changes and therefore result in changes in plasticity. Hebb’s postulate addresses this fact by stating that synaptic terminals are strengthened by correlated activity and will therefore sprout new branches. However, terminals that experience weakened and minimal activity will eventually lose their synaptic connection and deteriorate.
A major target of all molecular signaling is the inhibitory connections made by GABA
Gabâ
Gabâ or gabaa, for the people in many parts of the Philippines), is the concept of a non-human and non-divine, imminent retribution. A sort of negative karma, it is generally seen as an evil effect on a person because of their wrongdoings or transgressions...
ergic neurons. These receptors exist at postsynaptic sites and along with the regulation of local inhibitory synapses have been found to be very sensitive to critical period alterations. Any alteration to the receptors leads to changed concentrations of calcium
Calcium
Calcium is the chemical element with the symbol Ca and atomic number 20. It has an atomic mass of 40.078 amu. Calcium is a soft gray alkaline earth metal, and is the fifth-most-abundant element by mass in the Earth's crust...
in the affected cells and can ultimately influence dendritic and axonal branching. This concentration change is the result of many kinase
Kinase
In chemistry and biochemistry, a kinase is a type of enzyme that transfers phosphate groups from high-energy donor molecules, such as ATP, to specific substrates, a process referred to as phosphorylation. Kinases are part of the larger family of phosphotransferases...
s being activated, the byproduct of which may enhance specific gene expression.
Cell adhesion molecules (CAMs) are also important in plasticity as they help coordinate the signaling across the synapse. More specifically, integrins, which are receptors for extracellular matrix proteins and involved with CAMs, are explicitly incorporated in synapse maturation and memory formation. They play a crucial role in the feedback regulation of excitatory synaptic strength, or long-term potentiation
Long-term potentiation
In neuroscience, long-term potentiation is a long-lasting enhancement in signal transmission between two neurons that results from stimulating them synchronously. It is one of several phenomena underlying synaptic plasticity, the ability of chemical synapses to change their strength...
(LTP), and help to control synaptic strength by regulating AMPA
AMPA
AMPA is a compound that is a specific agonist for the AMPA receptor, where it mimics the effects of the neurotransmitter glutamate....
receptors, which result in quick, short synaptic currents. But, it is the metabotropic glutamate receptor 1 (mGlu1) that has been discovered to be required for activity-dependent synaptic plasticity in associative learning.
Activity-dependent plasticity is even seen in the primary visual cortex, a region of the brain that processes visual stimuli and is capable of modifying the experienced stimuli based on active sensing and arousal states. It is known that synaptic communication trends between excited and depressed states relative to the light/dark cycle. By experimentation on Long Evans rats, it was found that visual experience during vigilant states leads to increased responsiveness and plastic changes in the visual cortex. More so, depressed states were found to negatively alter the stimulus so the reaction was not as energetic. This experiment proves that even the visual cortex is capable of achieving activity-dependent plasticity as it is reliant on both visual exploration and the arousal state of the animal.
Role in learning
Activity-dependent plasticity plays a very large role in learning and in the ability of understanding new things. It is responsible for helping to adapt an individual’s brain according to the relative amount of usage and functioning. In essence, it is the brain’s ability to retain and develop memories based on activity-driven changes of synaptic strength that allow stronger learning of information. It is thought to be the growing and adapting quality of dendritic spineDendritic spine
A dendritic spine is a small membranous protrusion from a neuron's dendrite that typically receives input from a single synapse of an axon. Dendritic spines serve as a storage site for synaptic strength and help transmit electrical signals to the neuron's cell body...
s that provide the basis for synaptic plasticity connected to learning
Learning
Learning is acquiring new or modifying existing knowledge, behaviors, skills, values, or preferences and may involve synthesizing different types of information. The ability to learn is possessed by humans, animals and some machines. Progress over time tends to follow learning curves.Human learning...
and memory
Memory
In psychology, memory is an organism's ability to store, retain, and recall information and experiences. Traditional studies of memory began in the fields of philosophy, including techniques of artificially enhancing memory....
. Dendritic spines accomplish this by transforming synaptic input into neuronal output and also by helping to define the relationship between synapses.
In recent studies, a specific gene has also been identified as having a strong role in synapse growth and activity-dependent plasticity: the microRNA 132 gene (miR132). This gene is regulated by the cAMP response element-binding (CREB) protein pathway and is capable of enhancing dendritic growth when activated. The miR132 gene is another component that is responsible for the brain’s plasticity and helps to establish stronger connections between neurons.
Another plasticity-related gene involved in learning and memory is Arc/Arg3.1. The Arc gene is activity-regulated and the transcribed mRNA is localized to activated synaptic sites where the translated protein plays a role in AMPA receptor trafficking. Arc is a member of a class of proteins called immediate early genes that are rapidly transcribed in response to synaptic input. Of the estimated 30-40 genes that comprise the total neuronal IEG response, all are prototypical activity-dependent genes and a number have been implicated in learning and memory. For example, zif268
Zif268
EGR-1 also known as Zif268 or NGFI-A is a protein that in humans is encoded by the EGR1 gene....
, Arc
Arc (protein)
Arc, for activity-regulated cytoskeleton-associated protein , is a plasticity protein first characterized in 1995. Arc is a member of the immediate-early gene family, a rapidly activated class of genes functionally defined by their ability to be transcribed in the presence of protein synthesis...
, beta-activin, tPA
Tissue plasminogen activator
Tissue plasminogen activator is a protein involved in the breakdown of blood clots. It is a serine protease found on endothelial cells, the cells that line the blood vessels. As an enzyme, it catalyzes the conversion of plasminogen to plasmin, the major enzyme responsible for clot breakdown...
, Homer, and COX-2 have all been implicated in long-term potentiation
Long-term potentiation
In neuroscience, long-term potentiation is a long-lasting enhancement in signal transmission between two neurons that results from stimulating them synchronously. It is one of several phenomena underlying synaptic plasticity, the ability of chemical synapses to change their strength...
(LTP), a cellular correlate of learning and memory.
Mechanisms involved
There are a variety of mechanisms in place and being discovered from activity-dependent plasticity that work together to help the brain overcome problems and better adapt to functions. These include LTP, long-term depressionLong-term depression
Long-term depression , in neurophysiology, is an activity-dependent reduction in the efficacy of neuronal synapses lasting hours or longer. LTD occurs in many areas of the CNS with varying mechanisms depending upon brain region and developmental progress...
(LTD), synaptic elimination, neurogenesis
Neurogenesis
Neurogenesis is the process by which neurons are generated from neural stem and progenitor cells. Most active during pre-natal development, neurogenesis is responsible for populating the growing brain with neurons. Recently neurogenesis was shown to continue in several small parts of the brain of...
, and synaptogenesis
Synaptogenesis
Synaptogenesis is the formation of synapses. Although it occurs throughout a healthy person's lifespan, an explosion of synapse formation occurs during early brain development...
. The mechanisms of activity-dependent plasticity result in membrane depolarization and calcium
Calcium
Calcium is the chemical element with the symbol Ca and atomic number 20. It has an atomic mass of 40.078 amu. Calcium is a soft gray alkaline earth metal, and is the fifth-most-abundant element by mass in the Earth's crust...
influx, which in turn trigger cellular changes that affect synaptic connections and gene transcription
Transcription (genetics)
Transcription is the process of creating a complementary RNA copy of a sequence of DNA. Both RNA and DNA are nucleic acids, which use base pairs of nucleotides as a complementary language that can be converted back and forth from DNA to RNA by the action of the correct enzymes...
. In essence, neuronal activity helps to regulate gene expression
Gene expression
Gene expression is the process by which information from a gene is used in the synthesis of a functional gene product. These products are often proteins, but in non-protein coding genes such as ribosomal RNA , transfer RNA or small nuclear RNA genes, the product is a functional RNA...
for dendritic branching and synapse development while mutation
Mutation
In molecular biology and genetics, mutations are changes in a genomic sequence: the DNA sequence of a cell's genome or the DNA or RNA sequence of a virus. They can be defined as sudden and spontaneous changes in the cell. Mutations are caused by radiation, viruses, transposons and mutagenic...
s in activity-dependent transcription-related genes can lead to neurological disorders. Each of the studies’ findings aims to help proper development of the brain while improving a wide variety of tasks such as speech, movement, comprehension, and memory. More so, the findings better explain the development induced by plasticity.
It is known that during postnatal life a critical step to nervous system development is synapse elimination. The changes in synaptic connections and strength are results from LTP and LTD and are strongly regulated by the release of brain-derived neurotrophic factor
Brain-derived neurotrophic factor
Brain-derived neurotrophic factor, also known as BDNF, is a protein that, in humans, is encoded by the BDNF gene. BDNF is a member of the "neurotrophin" family of growth factors, which are related to the canonical "Nerve Growth Factor", NGF...
(BDNF), an activity-dependent synapse-development protein. In addition to BDNF, Nogo-66 receptors, and more specifically NgR1, are also involved in the development and regulation of neuronal structure. Damage to this receptor leads to pointless LTP and attenuation of LTD. Both situations imply that NgR1 is a regulator of synaptic plasticity. From experiments, it has been found that stimulation inducing LTD leads to a reduction in synaptic strength and loss of connections but, when coupled simultaneously with low-frequency stimulation, helps the restructuring of synaptic contacts. The implications of this finding include helping people with receptor damage and providing insight into the mechanism behind LTP.
Another mechanism that gives rise to activity-dependent plasticity includes the excitatory corticostriatal pathway that allows for the storage of adaptive motor behaviors. This pathway is also capable of adhering to long-lasting synaptic changes. The change in synaptic strength is responsible for motor learning and is dependent on the simultaneous activation of glutamatergic corticostriatal and dopaminergic nigrostriatal pathways. These are the very pathways that are affected in Parkinson's disease
Parkinson's disease
Parkinson's disease is a degenerative disorder of the central nervous system...
and the degeneration of synapses within this disorder may be responsible for the loss of cognitive abilities. Therefore, the impairment of DA/ACh-dependent learning can lead to the storage of inessential memories.
Mental retardation
Since plasticity is such a functional and necessary component of the brain, its proper functioning is necessary for healthy living since it accounts for brain construction/repair and storage. Mutations within any of the genes associated with activity-dependent plasticity have been found to positively correlate with various degrees of mental retardationMental retardation
Mental retardation is a generalized disorder appearing before adulthood, characterized by significantly impaired cognitive functioning and deficits in two or more adaptive behaviors...
. The two types of mental retardation related to plasticity depend on dysfunctional neuronal development or alterations in molecular mechanisms involved in synaptic organization. Complications within either of these types can greatly reduce brain function and more importantly brain capability and comprehension
Understanding
Understanding is a psychological process related to an abstract or physical object, such as a person, situation, or message whereby one is able to think about it and use concepts to deal adequately with that object....
.
Stroke rehabilitation
On the other hand, people with such conditions have the capacity to recover some degree of their lost abilities through continued challenges and use. A great example of this can be seen within Norman Doidge’s ‘The Brain That Changes Itself.’ Bach y Rita’s father suffered from a disabling strokeStroke
A stroke, previously known medically as a cerebrovascular accident , is the rapidly developing loss of brain function due to disturbance in the blood supply to the brain. This can be due to ischemia caused by blockage , or a hemorrhage...
that left the 65-year-old man half-paralyzed and unable to speak. After one year of crawling and unusual therapy tactics including playing basic children’s games and washing pots, his father’s rehabilitation was nearly complete and he went back to his role as a professor at City College in New York. The remarkable recovery from a stroke proves that even someone with abnormal behavior and severe medical complications can recover nearly all of the normal functions by much practice and perseverance: thus the message behind activity-dependent plasticity.
Recent studies have reported that a specific gene, FMR1, is highly involved in activity-dependent plasticity and Fragile X syndrome (FraX) is the result of this gene’s loss of function. FMR1 produces FMRP, which mediates activity-dependent control of synaptic structure. The loss or absence of this gene almost certainly leads to both autism
Autism
Autism is a disorder of neural development characterized by impaired social interaction and communication, and by restricted and repetitive behavior. These signs all begin before a child is three years old. Autism affects information processing in the brain by altering how nerve cells and their...
and mental retardation
Mental retardation
Mental retardation is a generalized disorder appearing before adulthood, characterized by significantly impaired cognitive functioning and deficits in two or more adaptive behaviors...
. Dr. Gatto has found that early introduction of the product FMRP results in nearly complete restructuring of the synapses. This method is not as effective, though, when introduced into a mature subject and only partially accommodates for the losses of FMR1. The discovery of this gene provides a possible location for intervention for young children with these abnormalities as this gene and its product act early to construct synaptic architecture.
Stress
A common issue amongst most people in the United States is high levels of stress and also disorders associated with continuous stress. Many regions of the brain are very sensitive to stress and can be damaged with extended exposure. More importantly, many of the mechanisms involved with increased memory retention, comprehensionUnderstanding
Understanding is a psychological process related to an abstract or physical object, such as a person, situation, or message whereby one is able to think about it and use concepts to deal adequately with that object....
, and adaptation is the result of LTP and LTD, two activity-dependent plasticity mechanisms that stress can directly suppress. Several experiments have been conducted in order to discover the specific mechanisms for this suppression and also possible intervention methods. Dr. Li and several others have actually identified the TRPV1 channel as a target to facilitate LTP and suppress LTD, therefore helping to protect the feature of synaptic plasticity and retention of memory from the effects of stress.
Future studies
The future studies and questions for activity-dependent plasticity are nearly endless because the implications of the findings will enable many treatments. Despite many gains within the field, there are a wide variety of disorders that further understanding would help treat and perhaps cure. These include autism, different severities of mental retardation, schizophreniaSchizophrenia
Schizophrenia is a mental disorder characterized by a disintegration of thought processes and of emotional responsiveness. It most commonly manifests itself as auditory hallucinations, paranoid or bizarre delusions, or disorganized speech and thinking, and it is accompanied by significant social...
, Parkinson’s Disease, stress, and stroke
Stroke
A stroke, previously known medically as a cerebrovascular accident , is the rapidly developing loss of brain function due to disturbance in the blood supply to the brain. This can be due to ischemia caused by blockage , or a hemorrhage...
victims. In addition to a better understanding of the various disorders, neurologists should and will look at the plasticity incurred by the immune system
Immune system
An immune system is a system of biological structures and processes within an organism that protects against disease by identifying and killing pathogens and tumor cells. It detects a wide variety of agents, from viruses to parasitic worms, and needs to distinguish them from the organism's own...
, as it will provide great insight into diseases and also give the basis of new immune-centered therapeutics. A better perspective of the cellular mechanisms that regulate neuronal morphology is the next step to discovering new treatments for learning and memory pathological conditions.
See also
- Central nervous systemCentral nervous systemThe central nervous system is the part of the nervous system that integrates the information that it receives from, and coordinates the activity of, all parts of the bodies of bilaterian animals—that is, all multicellular animals except sponges and radially symmetric animals such as jellyfish...
- Chemical synapseChemical synapseChemical synapses are specialized junctions through which neurons signal 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...
- Dendritic spineDendritic spineA dendritic spine is a small membranous protrusion from a neuron's dendrite that typically receives input from a single synapse of an axon. Dendritic spines serve as a storage site for synaptic strength and help transmit electrical signals to the neuron's cell body...
- Hebbian theoryHebbian theoryHebbian theory describes a basic mechanism for synaptic plasticity wherein an increase in synaptic efficacy arises from the presynaptic cell's repeated and persistent stimulation of the postsynaptic cell...
- NeuroplasticityNeuroplasticityNeuroplasticity is a non-specific neuroscience term referring to the ability of the brain and nervous system in all species to change structurally and functionally as a result of input from the environment. Plasticity occurs on a variety of levels, ranging from cellular changes involved in...
- PlasticityPlasticityPlasticity may refer to:Science* Plasticity , in physics and engineering, plasticity is the propensity of a material to undergo permanent deformation under load...
- Presynaptic and Postsynaptic
- Sensory substitutionSensory substitutionSensory substitution means to transform the characteristics of one sensory modality into stimuli of another sensory modality. It is hoped that sensory substitution systems can help handicapped people by restoring their ability to perceive a certain defective sensory modality by using sensory...
- Spike-timing-dependent plasticity