Homeostatic synaptic plasticity is a mechanism that helps maintain stable neuronal function in the face of changes in synapse number and strength during learning and development. This mechanism, known as synaptic scaling, allows neurons to detect changes in their firing rates through calcium-dependent sensors, which then regulate receptor trafficking to adjust the accumulation of glutamate receptors at synaptic sites. Other homeostatic mechanisms can lead to local or network-wide adjustments in the balance between excitation and inhibition. The signaling pathways underlying these mechanisms are currently under intense study, and while many molecular pathways have been implicated, a clear picture of how homeostatic feedback operates at the molecular level is still emerging. Neural circuits are subject to many destabilizing forces, such as long-term potentiation (LTP) and depression (LTD), which can lead to uncontrolled synaptic strengthening. Without homeostatic mechanisms, the specificity of synaptic connections can break down, making it difficult to store information effectively. Homeostatic plasticity mechanisms, such as synaptic scaling, help maintain stable firing rates by adjusting synaptic strength in response to changes in activity. These mechanisms can be global, affecting all synapses of a neuron, or local, acting on individual or small groups of synapses. In the neuromuscular junction (NMJ), homeostatic plasticity ensures that motor neurons can maintain the ability to activate muscle fibers despite changes in muscle properties. This is achieved through active signaling between motor neurons and muscle fibers, which helps maintain the gain of neuromuscular coupling. Studies in Drosophila have shown that presynaptic and postsynaptic changes can compensate for each other to maintain transmission efficiency. At central synapses, homeostatic plasticity is crucial for maintaining stable firing rates. Synaptic scaling is the best understood form of homeostatic plasticity, where changes in network activity lead to compensatory changes in synaptic strength. This process involves changes in the accumulation of glutamate receptors at synapses, which can be measured through miniature excitatory postsynaptic currents (mEPSCs). Synaptic scaling is a cell-autonomous process that can be induced by changes in firing rates and involves signaling pathways that regulate the expression of AMPA and NMDA receptors. Homeostatic plasticity also involves other mechanisms, such as changes in the balance between excitation and inhibition, compensatory changes in synapse number, and metaplastic mechanisms that adjust the ease of inducing LTP and LTD. These mechanisms work together to maintain stable neuronal function over a wide range of temporal and spatial scales. In vivo studies have shown that homeostatic plasticity is essential for proper circuit development and function. For example, during embryonic and early postnatal development, homeostatic mechanisms ensure that spontaneous activity is present in developing circuits, which is vital for proper connectivity. In visual cortex, homeostatic plasticity helps match local microcircuit excitability to the strength of sensory drive, ensuring that synaptic strength is adjusted appropriately.Homeostatic synaptic plasticity is a mechanism that helps maintain stable neuronal function in the face of changes in synapse number and strength during learning and development. This mechanism, known as synaptic scaling, allows neurons to detect changes in their firing rates through calcium-dependent sensors, which then regulate receptor trafficking to adjust the accumulation of glutamate receptors at synaptic sites. Other homeostatic mechanisms can lead to local or network-wide adjustments in the balance between excitation and inhibition. The signaling pathways underlying these mechanisms are currently under intense study, and while many molecular pathways have been implicated, a clear picture of how homeostatic feedback operates at the molecular level is still emerging. Neural circuits are subject to many destabilizing forces, such as long-term potentiation (LTP) and depression (LTD), which can lead to uncontrolled synaptic strengthening. Without homeostatic mechanisms, the specificity of synaptic connections can break down, making it difficult to store information effectively. Homeostatic plasticity mechanisms, such as synaptic scaling, help maintain stable firing rates by adjusting synaptic strength in response to changes in activity. These mechanisms can be global, affecting all synapses of a neuron, or local, acting on individual or small groups of synapses. In the neuromuscular junction (NMJ), homeostatic plasticity ensures that motor neurons can maintain the ability to activate muscle fibers despite changes in muscle properties. This is achieved through active signaling between motor neurons and muscle fibers, which helps maintain the gain of neuromuscular coupling. Studies in Drosophila have shown that presynaptic and postsynaptic changes can compensate for each other to maintain transmission efficiency. At central synapses, homeostatic plasticity is crucial for maintaining stable firing rates. Synaptic scaling is the best understood form of homeostatic plasticity, where changes in network activity lead to compensatory changes in synaptic strength. This process involves changes in the accumulation of glutamate receptors at synapses, which can be measured through miniature excitatory postsynaptic currents (mEPSCs). Synaptic scaling is a cell-autonomous process that can be induced by changes in firing rates and involves signaling pathways that regulate the expression of AMPA and NMDA receptors. Homeostatic plasticity also involves other mechanisms, such as changes in the balance between excitation and inhibition, compensatory changes in synapse number, and metaplastic mechanisms that adjust the ease of inducing LTP and LTD. These mechanisms work together to maintain stable neuronal function over a wide range of temporal and spatial scales. In vivo studies have shown that homeostatic plasticity is essential for proper circuit development and function. For example, during embryonic and early postnatal development, homeostatic mechanisms ensure that spontaneous activity is present in developing circuits, which is vital for proper connectivity. In visual cortex, homeostatic plasticity helps match local microcircuit excitability to the strength of sensory drive, ensuring that synaptic strength is adjusted appropriately.