# Homeostatic plasticity

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' (a product of the Greek words for 'same' and 'state' or 'condition') and plasticity (or 'change'), 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.

## Types

The capacity of neurons to sustain consistent activity levels in response to variations in synaptic input is known as homeostatic synaptic plasticity. Homeostatic synaptic plasticity occurs when neurons modify their synaptic strength in response to variations in activity levels to preserve network stability. This response serves to keep neuronal circuits in the appropriate range of activity for proper functioning. Homeostatic synaptic plasticity can be shown in synaptic scaling, postsynaptic receptor expression, presynaptic alterations, and dendritic spine remodeling.

### Presynaptic

Homeostatic presynaptic plasticity refers to the ability of neurons to regulate neurotransmitter release at presynaptic terminals, ensuring a steady range of brain activity. This process involves various mechanisms, such as quantal size adjustment, differential expression of presynaptic proteins, and modification of vesicle recycling. Quantal size adjustment helps maintain steady postsynaptic responses despite changes in synaptic strength. Differential expression of presynaptic proteins, such as calcium channels or synaptic vesicle proteins, can also be altered by neurons to affect neurotransmitter release rate.

### Postsynaptic

Homeostatic postsynaptic plasticity is crucial for maintaining consistent levels of synaptic activity in neurons, which are formed at specific synapses in the brain. Homeostatic processes involve changes in the expression of receptors, changes in receptor subunit composition, and changes to intracellular signaling pathways. For example, the NMDA receptor can change its subunit composition to improve sensitivity to neurotransmitters. Additionally, changes in the expression and location of neurotransmitter receptors can impact synaptic transmission when specific signaling pathways are activated. Synaptic adhesion molecules can also be influenced by homeostatic processes. Overall, homeostatic postsynaptic plasticity contributes to the stability and proper functioning of neural circuits, allowing the brain to adapt to changing conditions without compromising the overall stability of neuronal activity.

### Intrinsic

Homeostatic intrinsic plasticity refers to the ability of neurons to change their intrinsic electrical characteristics in response to changes in synaptic or network activity. This process involves alterations in the excitability or firing characteristics of individual neurons, rather than primarily adjusting synaptic strength. Intrinsic plasticity processes associated with homeostasis include ion channel expression alterations, membrane conductance modifications, action potential threshold alterations, and regulation of intrinsic excitability. Neurons can upregulate the expression of sodium channels to maintain firing rates and increase excitability in case of a drop in synaptic activity. These changes impact the input-output link between neurons and the homeostatic control of neuronal activity.

### Synaptic scaling

Synaptic scaling is a homeostatic mechanism that allows neurons to modulate the strength of all synapses to maintain stable activity levels within a specific range. This process is characterized by changes in the quantity or sensitivity of neurotransmitter receptors on the postsynaptic membrane. Neurons can reduce the number of neurotransmitter receptors in response to network activity spikes, reducing synaptic strength, or increase the density in response to network activity drops, increasing sensitivity and boosting synaptic strength. This homeostatic regulation of brain circuits supports other types of synaptic plasticity, such as long-term depression and long-term potentiation.

## Comparison with Hebbian plasticity

Homeostatic synaptic plasticity is a means of maintaining the synaptic basis for learning, respiration, and locomotion, in contrast to the Hebbian plasticity associated with learning and memory. Although Hebbian forms of plasticity, such as long-term potentiation and long-term depression occur rapidly, homeostatic plasticity (which relies on protein synthesis) can take hours or days. TNF-α and microRNAs are important mediators of homeostatic synaptic plasticity.
Homeostatic plasticity is thought to balance Hebbian plasticity by modulating the activity of the synapse or the properties of ion channels. Homeostatic plasticity in neocortical circuits has been studied in depth by Gina G. Turrigiano and Sacha Nelson of Brandeis University, who first observed compensatory changes in excitatory postsynaptic currents (mEPSCs) after chronic activity manipulations.

### Long-term

Long-term potentiation (LTP) and long-term depression (LTD) are example of Hebbian plasticity. This means that these terms also have to do with the brain, synaptic strength, and how memory/learning are processed. Long-term potentiation is a type of plasticity where the communication between neurons is improved over a long period of time. Long-term depression would be when this activity in the synapses are reduced. These terms are theorized to be responsible for the storage of memory, but it has not been officially confirmed. Another term that sums up LTP and LTD is synaptic plasticity, which describes this synaptic strength in the brain.

## Comparison to other types of plasticity
### Functional

A type of neuroplasticity that discusses the plasticity of the brain when facing injuries. The functions and abilities of a certain part of the brain can be moved to another part of the brain when damaged. For example, as the left and right side of the brain have certain functions, removing one side entirely may result in the remaining side to take over those abilities. This helps avoid the issue of the organism losing important functions needed for survival.

### Structural

Another type of neuroplasticity that, as the name suggests, involves the actual structure of the brain changing as a result of learning, as opposed to just synapses. But as amazing as the brain is, there is only so far that an organ this complex can push itself.

## Mechanism

Synaptic scaling has been proposed as a potential mechanism of homeostatic plasticity. Homeostatic plasticity can be used to describe a process that maintains the stability of neuronal functions through a coordinated plasticity among subcellular compartments, such as the synapses versus the neurons and the cell bodies versus the axons. Recently, it was proposed that homeostatic synaptic scaling may play a role in establishing the specificity of an associative memory.
Homeostatic plasticity also maintains neuronal excitability in a real-time manner through the coordinated plasticity of threshold and refractory period at voltage-gated sodium channels.

## Role in central pattern generators

Homeostatic plasticity is also very important in the context of central pattern generators. In this context, neuronal properties are modulated in response to environmental changes in order to maintain an appropriate and balanced neural output. There is evidence central pattern generators use a mixed strategy of homeostatic plasticity to achieve stability.

## Role in neurological disorders

Homeostatic plasticity plays a crucial role in neurological disorders such as epilepsy, autism, Alzheimer's disease, and other neurodegenerative diseases. In these disorders, neurons ability to maintain stability in response to changes in activity levels or external stimuli is often altered.

### Epilepsy

In a healthy brain, neuronal excitability and synaptic strength are homeostatically regulated to maintain balance between excitation and inhibition. In an epileptic brain, homeostatic plasticity mechanisms may become dysregulated leading to episodes of highly synchronized neuronal firing and seizure activity. It is still unclear how homeostatic compensation is involved in epileptogenic processes. Traditional pharmacological approaches may be ineffective in restoring physiological balance in the neuronal network. However, therapeutic strategies targeting homeostatic plasticity mechanisms may offer a potential solution.

### Autism

Homeostatic plasticity is vital for maintaining the neurological balance in the brain. An imbalance between excitatory and inhibitory neurotransmissions in the brain can lead to Autism spectrum disorder. Dysregulation of homeostatic plasticity and neural imbalance can contribute to the cognitive and behavioral symptoms associated with autism.

### Alzheimer's disease

In Alzheimer's disease, synaptic function and neuronal integrity are impaired. In a healthy brain, these mechanisms are tightly maintained by homeostatic plasticity. Deficits in homeostatic plasticity contribute to cognitive decline and memory impairment which are characteristic symptoms of Alzheimer's disease.

### Neurodegenerative diseases

Several neurological disorders are affected by homeostatic plasticity. Dysregulation of homeostatic plasticity can cause an excitatory or inhibitory network activity. Parkinson's disease, Huntington's disease, and ALS are all examples of disorder where dysregulation of neuronal network contribute to the pathophysiology of the disorders.

### Schizophrenia

Schizophrenia is characterized by disruptions in thought processes, perceptions, and emotions. Alterations in synaptic strength and connectivity potentially due to dysregulation in homeostatic mechanisms may lead to the symptoms observed in schizophrenic patients. These dysregulation contribute to the cognitive deficits and delusions observed in schizophrenia. In fact, a study was conducted to prove that disturbance in the homeostasis of Purkinje cells is an example of how developmental plasticity homeostasis is crucial in preventing mental illnesses like Schizophrenia. Purkinje cells are neurons located in the cerebellum and are involved in cognitive functions. Moreover, research has shown that Purkinje cells keep the brain’s activity stable after traumatic experiences, and unregulated responses to trauma disrupt normal brain activity, which leads to mental illnesses.

## Prominent researchers

Gina G. Turrigiano is an American neuroscientist known for her work on homeostatic plasticity mechanisms in the brain. Her research focused on synaptic strength and intrinsic excitability of neurons. She made key discoveries in synaptic scaling, synaptic plasticity, and other molecular mechanisms related to homeostatic regulation.