Homeostatic regulation of neuronal function: importance of degeneracy and pleiotropy DOI Creative Commons
Jane Yang, Steven A. Prescott

Frontiers in Cellular Neuroscience, Journal Year: 2023, Volume and Issue: 17

Published: June 2, 2023

Neurons maintain their average firing rate and other properties within narrow bounds despite changing conditions. This homeostatic regulation is achieved using negative feedback to adjust ion channel expression levels. To understand how of excitability normally works it goes awry, one must consider the various channels involved as well regulated impacted by adjusting those when regulating excitability. raises issues degeneracy pleiotropy. Degeneracy refers disparate solutions conveying equivalent function (e.g., different combinations yielding excitability). many-to-one mapping contrasts one-to-many described pleiotropy affecting multiple properties). facilitates enabling a disturbance be offset compensatory changes in any several or thereof. Pleiotropy complicates because intended regulate property may inadvertently disrupt properties. Co-regulating pleiotropic requires greater than isolation and, extension, can fail for additional reasons such each being incompatible with another. Problems also arise if perturbation too strong and/or weak, set point disturbed. Delineating loops interactions provides valuable insight into might fail. Insofar failure modes require distinct interventions restore homeostasis, deeper understanding its pathological disruption reveal more effective treatments chronic neurological disorders like neuropathic pain epilepsy.

Language: Английский

The Biology of Forgetting—A Perspective DOI Creative Commons
Ronald L. Davis, Yi Zhong

Neuron, Journal Year: 2017, Volume and Issue: 95(3), P. 490 - 503

Published: Aug. 1, 2017

Language: Английский

Citations

274
Homeostatic Control of Presynaptic Neurotransmitter Release DOI
Graeme W. Davis, Martin Müller

Annual Review of Physiology, Journal Year: 2014, Volume and Issue: 77(1), P. 251 - 270

Published: Nov. 11, 2014

It is well established that the active properties of nerve and muscle cells are stabilized by homeostatic signaling systems. In organisms ranging from Drosophila to humans, neurons restore baseline function in continued presence destabilizing perturbations rebalancing ion channel expression, modifying neurotransmitter receptor surface expression trafficking, modulating release. This review focuses on modulation presynaptic release, termed homeostasis. First, we highlight criteria can be used define a process as being under control. Next, remarkable conservation homeostasis at Drosophila, mouse, human neuromuscular junctions emerging parallels synaptic connections mammalian central nervous system. We then recent progress identifying cellular molecular mechanisms. conclude reviewing between mechanisms genetic links neurological disease.

Language: Английский

Citations

263
Alzheimer’s Disease: From Firing Instability to Homeostasis Network Collapse DOI Creative Commons
Samuel Frère, Inna Slutsky

Neuron, Journal Year: 2018, Volume and Issue: 97(1), P. 32 - 58

Published: Jan. 1, 2018

Language: Английский

Citations

222
Hebbian plasticity requires compensatory processes on multiple timescales DOI Creative Commons
Friedemann Zenke, Wulfram Gerstner

Philosophical Transactions of the Royal Society B Biological Sciences, Journal Year: 2017, Volume and Issue: 372(1715), P. 20160259 - 20160259

Published: Jan. 17, 2017

We review a body of theoretical and experimental research on Hebbian homeostatic plasticity, starting from puzzling observation: while homeostasis synapses found in experiments is slow compensatory process, most mathematical models synaptic plasticity use rapid processes (RCPs). Even worse, with the reported experiments, simulations existing cannot maintain network stability unless further control mechanisms are implemented. To solve this paradox, we suggest that addition to forms there RCPs which stabilize short timescales. These may include heterosynaptic depression triggered by episodes high postsynaptic firing rate. While slower not sufficient they important for fine-tuning neural circuits. Taken together learning memory rely an intricate interplay diverse different timescales jointly ensure This article part themed issue ‘Integrating plasticity’.

Language: Английский

Citations

194
Transmission, Development, and Plasticity of Synapses DOI Open Access
Kathryn P. Harris, J. Troy Littleton

Genetics, Journal Year: 2015, Volume and Issue: 201(2), P. 345 - 375

Published: Oct. 1, 2015

Abstract Chemical synapses are sites of contact and information transfer between a neuron its partner cell. Each synapse is specialized junction, where the presynaptic cell assembles machinery for release neurotransmitter, postsynaptic components to receive integrate this signal. Synapses also exhibit plasticity, during which synaptic function and/or structure modified in response activity. With robust panel genetic, imaging, electrophysiology approaches, strong evolutionary conservation molecular components, Drosophila has emerged as an essential model system investigating mechanisms underlying assembly, function, plasticity. We will discuss techniques studying Drosophila, with focus on larval neuromuscular junction (NMJ), well-established glutamatergic synapse. Vesicle fusion, underlies neurotransmitters, been well characterized at In addition, studies assembly organization active zones densities have revealed pathways that coordinate those events across cleft. review modes growth plasticity fly NMJ, how pre- cells communicate regulate

Language: Английский

Citations

193
Circuit and Synaptic Plasticity Mechanisms of Drug Relapse DOI Creative Commons
Yan Dong, Jane R. Taylor, Marina E. Wolf

et al.

Journal of Neuroscience, Journal Year: 2017, Volume and Issue: 37(45), P. 10867 - 10876

Published: Nov. 8, 2017

High rates of relapse to drug use during abstinence is a defining feature human addiction. This clinical scenario has been studied at the preclinical level using different animal models in which seeking assessed after cessation operant self-administration rodents and monkeys. In our Society for Neuroscience (SFN) session entitled “Circuit Synaptic Plasticity Mechanisms Drug Relapse,” we will discuss new developments understanding circuits synaptic plasticity mechanisms from studies combining established novel with state-of-the-art cellular, electrophysiology, anatomical, chemogenetic, optogenetic methods. We also translational implications these developments. mini-review that introduces SFN session, summarize results laboratories on behavioral, circuit within context session.

Language: Английский

Citations

164
Nascent Proteome Remodeling following Homeostatic Scaling at Hippocampal Synapses DOI Creative Commons

Christoph T Schanzenbächer,

Sivakumar Sambandan, Julian D. Langer

et al.

Neuron, Journal Year: 2016, Volume and Issue: 92(2), P. 358 - 371

Published: Oct. 1, 2016

Language: Английский

Citations

149
High Dietary Sugar Reshapes Sweet Taste to Promote Feeding Behavior in Drosophila melanogaster DOI Creative Commons
Christina E. May, Anoumid Vaziri,

Yong Lin

et al.

Cell Reports, Journal Year: 2019, Volume and Issue: 27(6), P. 1675 - 1685.e7

Published: May 1, 2019

Recent studies find that sugar tastes less intense to humans with obesity, but whether this sensory change is a cause or consequence of obesity unclear. To tackle question, we study the effects high diet on sweet taste sensation and feeding behavior in Drosophila melanogaster. On diet, fruit flies have lower responses stimuli, overconsume food, develop obesity. Excess dietary sugar, not sweetness alone, caused deficits overeating via cell-autonomous action sensor O-linked N-Acetylglucosamine (O-GlcNAc) transferase (OGT) sweet-sensing neurons. Correcting by manipulating excitability gustatory neurons levels OGT protected animals from diet-induced Our work demonstrates reshaping excess drives highlights role glucose metabolism neural activity behavior.

Language: Английский

Citations

138
Mitochondrial Regulation of the Hippocampal Firing Rate Set Point and Seizure Susceptibility DOI Creative Commons

Boaz Styr,

N Gonen,

Daniel Zarhin

et al.

Neuron, Journal Year: 2019, Volume and Issue: 102(5), P. 1009 - 1024.e8

Published: April 29, 2019

Maintaining average activity within a set-point range constitutes fundamental property of central neural circuits. However, whether and how set points are regulated remains unknown. Integrating genome-scale metabolic modeling experimental study neuronal homeostasis, we identified mitochondrial dihydroorotate dehydrogenase (DHODH) as regulator in hippocampal networks. The DHODH inhibitor teriflunomide stably suppressed mean firing rates via synaptic intrinsic excitability mechanisms by modulating Ca

Language: Английский

Citations

125
Homeostatic plasticity in neural development DOI Creative Commons

Nai-Wen Tien,

Daniel Kerschensteiner

Neural Development, Journal Year: 2018, Volume and Issue: 13(1)

Published: May 14, 2018

Throughout life, neural circuits change their connectivity, especially during development, when neurons frequently extend and retract dendrites axons, form eliminate synapses. In spite of changing maintain relatively constant activity levels. Neural achieve functional stability by homeostatic plasticity, which equipoises intrinsic excitability synaptic strength, balances network excitation inhibition, coordinates changes in circuit connectivity. Here, we review how diverse mechanisms plasticity stabilize developing circuits.

Language: Английский

Citations

114