Homeostatic Synaptic Plasticity: Local and Global Mechanisms for Stabilizing Neuronal Function

Homeostatic plasticity has emerged as a fundamental regulatory principle that strives to maintain neuronal activity within optimal ranges by altering diverse aspects of neuronal function. Adaptation to network activity is often viewed as an essential negative feedback restraint that prevents runaway excitation or inhibition. However, the precise importance of these homeostatic functions is often theoretical rather than empirically derived. Moreover, a remarkable multiplicity of homeostatic adaptations has been observed. To clarify these issues, it may prove useful to ask: why do homeostatic mechanisms exist, what advantages do these adaptive responses confer on a given cell population, and why are there so many seemingly divergent effects? Here, we approach these questions by applying the principles of control theory to homeostatic synaptic plasticity of mammalian neurons and suggest that the varied responses observed may represent distinct functional classes of control mechanisms directed toward disparate physiological goals.

Download Full-text

Faculty Opinions recommendation of MicroRNA miR124 is required for the expression of homeostatic synaptic plasticity.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.725975736.793542883 ◽

2018 ◽

Author(s):

Johannes Hell

Keyword(s):

Synaptic Plasticity ◽

Homeostatic Synaptic Plasticity

Download Full-text

Faculty Opinions recommendation of Control of Homeostatic Synaptic Plasticity by AKAP-Anchored Kinase and Phosphatase Regulation of Ca2+-Permeable AMPA Receptors.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.732664991.793544181 ◽

2018 ◽

Author(s):

Johannes Hell

Keyword(s):

Synaptic Plasticity ◽

Ampa Receptors ◽

Homeostatic Synaptic Plasticity ◽

Phosphatase Regulation

Download Full-text

Retinoic Acid Receptor RARα-Dependent Synaptic Signaling Mediates Homeostatic Synaptic Plasticity at the Inhibitory Synapses of Mouse Visual Cortex

Journal of Neuroscience ◽

10.1523/jneurosci.1133-18.2018 ◽

2018 ◽

Vol 38 (49) ◽

pp. 10454-10466 ◽

Cited By ~ 8

Author(s):

Lei R. Zhong ◽

Xin Chen ◽

Esther Park ◽

Thomas C. Südhof ◽

Lu Chen

Keyword(s):

Retinoic Acid ◽

Synaptic Plasticity ◽

Visual Cortex ◽

Retinoic Acid Receptor ◽

Inhibitory Synapses ◽

Acid Receptor ◽

Synaptic Signaling ◽

Homeostatic Synaptic Plasticity ◽

Mouse Visual Cortex

Download Full-text

Homeostatic synaptic depression is achieved through a regulated decrease in presynaptic calcium channel abundance

eLife ◽

10.7554/elife.05473 ◽

2015 ◽

Vol 4 ◽

Cited By ~ 34

Author(s):

Michael A Gaviño ◽

Kevin J Ford ◽

Santiago Archila ◽

Graeme W Davis

Keyword(s):

Synaptic Plasticity ◽

Neuromuscular Junction ◽

Action Potential ◽

Calcium Channel ◽

Neurotransmitter Release ◽

Calcium Influx ◽

Homeostatic Synaptic Plasticity ◽

Action Potential Waveform ◽

Presynaptic Calcium ◽

Potential Waveform

Homeostatic signaling stabilizes synaptic transmission at the neuromuscular junction (NMJ) of Drosophila, mice, and human. It is believed that homeostatic signaling at the NMJ is bi-directional and considerable progress has been made identifying mechanisms underlying the homeostatic potentiation of neurotransmitter release. However, very little is understood mechanistically about the opposing process, homeostatic depression, and how bi-directional plasticity is achieved. Here, we show that homeostatic potentiation and depression can be simultaneously induced, demonstrating true bi-directional plasticity. Next, we show that mutations that block homeostatic potentiation do not alter homeostatic depression, demonstrating that these are genetically separable processes. Finally, we show that homeostatic depression is achieved by decreased presynaptic calcium channel abundance and calcium influx, changes that are independent of the presynaptic action potential waveform. Thus, we identify a novel mechanism of homeostatic synaptic plasticity and propose a model that can account for the observed bi-directional, homeostatic control of presynaptic neurotransmitter release.

Download Full-text

Astrocyte-secreted IL-33 mediates homeostatic synaptic plasticity in the adult hippocampus

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.2020810118 ◽

2020 ◽

Vol 118 (1) ◽

pp. e2020810118

Author(s):

Ye Wang ◽

Wing-Yu Fu ◽

Kit Cheung ◽

Kwok-Wang Hung ◽

Congping Chen ◽

...

Keyword(s):

Synaptic Plasticity ◽

Neuronal Activity ◽

Hippocampal Slices ◽

Memory Formation ◽

Conditional Knockout ◽

Acute Administration ◽

Excitatory Synapses ◽

Homeostatic Synaptic Plasticity ◽

Hippocampal Ca1

Hippocampal synaptic plasticity is important for learning and memory formation. Homeostatic synaptic plasticity is a specific form of synaptic plasticity that is induced upon prolonged changes in neuronal activity to maintain network homeostasis. While astrocytes are important regulators of synaptic transmission and plasticity, it is largely unclear how they interact with neurons to regulate synaptic plasticity at the circuit level. Here, we show that neuronal activity blockade selectively increases the expression and secretion of IL-33 (interleukin-33) by astrocytes in the hippocampal cornu ammonis 1 (CA1) subregion. This IL-33 stimulates an increase in excitatory synapses and neurotransmission through the activation of neuronal IL-33 receptor complex and synaptic recruitment of the scaffold protein PSD-95. We found that acute administration of tetrodotoxin in hippocampal slices or inhibition of hippocampal CA1 excitatory neurons by optogenetic manipulation increases IL-33 expression in CA1 astrocytes. Furthermore, IL-33 administration in vivo promotes the formation of functional excitatory synapses in hippocampal CA1 neurons, whereas conditional knockout of IL-33 in CA1 astrocytes decreases the number of excitatory synapses therein. Importantly, blockade of IL-33 and its receptor signaling in vivo by intracerebroventricular administration of its decoy receptor inhibits homeostatic synaptic plasticity in CA1 pyramidal neurons and impairs spatial memory formation in mice. These results collectively reveal an important role of astrocytic IL-33 in mediating the negative-feedback signaling mechanism in homeostatic synaptic plasticity, providing insights into how astrocytes maintain hippocampal network homeostasis.

Download Full-text