Modern neuroscience has increasingly noted the importance of neuroplasticity in nervous system development. In summary, neuroplasticity is defined as the brain's ability to adapt the structure and function of its own neurons to the external changes in the environment, supporting processes such as learning, memory creation, healing from injury, and overall development. Traditional Hebbian plasticity, which is the most well-studied form of neuroplasticity, states that repeated action and experiences strengthen synapses (long-term potentiation) and lack of action and experiences weaken or diminish synapses (long-term depression). However, this can lead to potential instability in the nervous system, where synapses and nerves can saturate to either extremes, either firing constantly or not firing at all. In response, the nervous system can also perform homeostatic plasticity. Being a subset of neuroplasticity, homeostatic plasticity specifically acts as the brain's "self-correcting" counterforce. It acts as the nervous system's "thermostat", bringing neural activity back to specific balanced set point when it becomes too high or too low in certain regions of the brain. Homeostatic plasticity is 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, the neural circuit has to remain stable in function through a variety of fluctuating changes that occur in the number and strength of synaptic connections. Thus, neurons must be able to keep track of and evolve with their changing environment while ensuring there is stability on the functional and structural level. Hebbian neuroplasticity (the neuroplasticity that causes long-term potentiation and long-term depression) creates changes that pushes neural circuits away from equilibrium, and it is important to ensure that stability is still maintained for neurons to maintain their activity and functionality. Neurons need to have flexibility to adapt to changes in the connectivity and synaptic strength during development and learning, but they must also have a system in place to keep them in check. This is the purpose of homeostatic plasticity: the neuronal networks use a complex set of regulatory mechanisms to achieve homeostasis over a wide range of temporal and spatial scales. Whenever there is a perturbation to the nervous system, such as a synaptic connection or neural circuit that is over-excited to the point of harm, homeostatic plasticity mechanisms are triggered and circuit functions are stabilized. Homeostatic plasticity acts as a negative feedback mechanism. Since this mechanism is used to offset the excessive excitation or inhibition through adjusting the synaptic strength of the neurons, it maintains stability by reversing a change. Homeostatic plasticity has its own mechanism, subtypes, and comparators. Additionally, homeostatic plasticity can be connected to the nervous system by exploring its general purpose and roles in the system, specifically with central pattern generators and in neurological disorders. The remainder of this article will cover all important facets needed for thorough understanding homeostatic plasticity and the implication it has on clinical diseases and future research, including the topics mentioned above.
Mechanisms
While the way that homeostatic plasticity is induced is still being studied, there are many ongoing research projects and past projects that have uncovered details on the mechanisms that allow the negative feedback loop of homeostatic plasticity to take place. Key findings suggest that two main mechanisms behind homeostatic plasticity are intrinsic excitability and synaptic efficacy. Synaptic scaling has been labeled as a potential mechanism of homeostatic plasticity. Homeostatic plasticity is often used to describe a process that maintains 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. Synaptic scaling aids in that regulation of neurons as the role of synaptic scaling is to adjust the strength of neuron's excitatory synapses, helping to keep the neurons in check so homeostatic plasticity can achieve its function properly. In 2021, it was proposed that homeostatic synaptic scaling may play a role in establishing the specificity of an associative memory. In 2025, it was found that the protein LARGE plays a significant role in homeostatic resetting of Hebbian plasticity through the downregulation of AMPA-receptor trafficking in the Golgi apparatus. Other studies have stated that phosphorylation is another method in which homeostatic plasticity can be stimulated. Research has also shown that heterosynaptic plasticity can act as an underlying mechanism for homeostatic plasticity in undoing the positive-feedback loop effects of Hebbian plasiticity. Homeostatic plasticity also uses a separate mechanism to help maintain neuronal excitability in a real-time manner through the coordinated plasticity of threshold and refractory period at voltage-gated sodium channels, keeping them balanced so the barrier remains constant for stable firing actions. Homeostatic plasticity can also be mediated by extracellular signals such as BDNF or TNF-α. These factors are released in an activity-dependent manner and can regulate both excitatory and inhibitory synapses across neurons, contributing to circuit-wide homeostatic adjustments. There is often an overlap between the mechanisms behind homeostatic plasticity and the sub-types of homeostatic plasticity, as the sub-types play an important role in ensuring that homeostasis is achieved within neural networks.
Sub-types Homeostatic plasticity serves to keep neuronal circuits in the appropriate range of activity for proper functioning. Homeostatic synaptic plasticity can be shown in presynaptic alterations, postsynaptic receptor expression, changes in intrinsic characteristics, synaptic scaling, structural homeostatic plasticity, and metaplasticity.
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![Homeostatic plasticity: Presynaptic terminal[10][circular reference]](https://upload.wikimedia.org/wikipedia/commons/thumb/5/50/Synapse_figure.png/1280px-Synapse_figure.png?utm_source=en.wikipedia.org&utm_campaign=parser&utm_content=thumbnail)
![Homeostatic plasticity: Purjunkie cells in neurons[46][circular reference]](https://upload.wikimedia.org/wikipedia/commons/thumb/2/28/Neurons_%28Purkinje_cells%29.jpg/1280px-Neurons_%28Purkinje_cells%29.jpg?utm_source=en.wikipedia.org&utm_campaign=parser&utm_content=thumbnail)
