Loss of Depalmitoylation Disrupts Homeostatic Plasticity of AMPARs in a Mouse Model of Infantile Neuronal Ceroid Lipofuscinosis DOI Creative Commons
Kevin P. Koster, Edén Flores-Barrera, Emilce Artur de la Villarmois

et al.

Journal of Neuroscience, Journal Year: 2023, Volume and Issue: 43(49), P. 8317 - 8335

Published: Oct. 26, 2023

Protein palmitoylation is the only reversible post-translational lipid modification. Palmitoylation held in delicate balance by depalmitoylation to precisely regulate protein turnover. While over 20 enzymes are known, conducted fewer enzymes. Of particular interest lack of depalmitoylating enzyme palmitoyl-protein thioesterase 1 (PPT1) that causes devastating pediatric neurodegenerative condition infantile neuronal ceroid lipofuscinosis (CLN1). most research on Ppt1 function has centered its role lysosome, recent findings demonstrated many substrates synaptic proteins, including AMPA receptor (AMPAR) subunit GluA1. Still, impact Ppt1-mediated transmission and plasticity remains elusive. Thus, goal present study was use −/− mouse model (both sexes) determine whether regulates AMPAR-mediated plasticity, which crucial for maintenance homeostatic adaptations cortical circuits. Here, we found basal excitatory visual cortex developmentally regulated chemogenetic silencing excessively enhanced expression Furthermore, triggering primary neurons caused an exaggerated incorporation GluA1-containing, calcium-permeable AMPARs, correlated with increased GluA1 palmitoylation. Finally, Ca 2+ imaging awake mice showed favor a state synchronous firing. Collectively, our results elucidate AMPAR trafficking show impeded proteostasis palmitoylated proteins drives maladaptive abnormal recruitment activity CLN1. SIGNIFICANCE STATEMENT Neuronal communication orchestrated movement receptors from membrane. modification, process must be balanced depalmitoylation. The significance evidenced discovery mutation (Ppt1) severe neurodegeneration. In this study, equilibrium provided critical (AMPAR)-mediated associated This finding complements explosion emphasizing necessity

Language: Английский

Hypothalamus-habenula potentiation encodes chronic stress experience and drives depression onset DOI Creative Commons
Zhiwei Zheng, Guo Chen, Min Li

et al.

Neuron, Journal Year: 2022, Volume and Issue: 110(8), P. 1400 - 1415.e6

Published: Feb. 2, 2022

Language: Английский

Citations

111
Dynamic and selective engrams emerge with memory consolidation DOI Creative Commons
Douglas Feitosa Tomé, Ying Zhang, Tomomi Aida

et al.

Nature Neuroscience, Journal Year: 2024, Volume and Issue: 27(3), P. 561 - 572

Published: Jan. 19, 2024

Episodic memories are encoded by experience-activated neuronal ensembles that remain necessary and sufficient for recall. However, the temporal evolution of memory engrams after initial encoding is unclear. In this study, we employed computational experimental approaches to examine how neural composition selectivity change with consolidation. Our spiking network model yielded testable predictions: transition from unselective selective as neurons drop out into engrams; inhibitory activity during recall essential selectivity; synaptic plasticity consolidation critical become selective. Using activity-dependent labeling, longitudinal calcium imaging a combination optogenetic chemogenetic manipulations in mouse dentate gyrus, conducted contextual fear conditioning experiments supported our model's predictions. results reveal dynamic changes engram mediated crucial emergence selectivity.

Language: Английский

Citations

19
Keeping Your Brain in Balance: Homeostatic Regulation of Network Function DOI
Wei Wen, Gina G. Turrigiano

Annual Review of Neuroscience, Journal Year: 2024, Volume and Issue: 47(1), P. 41 - 61

Published: Feb. 21, 2024

To perform computations with the efficiency necessary for animal survival, neocortical microcircuits must be capable of reconfiguring in response to experience, while carefully regulating excitatory and inhibitory connectivity maintain stable function. This dynamic fine-tuning is accomplished through a rich array cellular homeostatic plasticity mechanisms that stabilize important network features such as firing rates, information flow, sensory tuning properties. Further, these functional properties can stabilized by different forms plasticity, including target or synapses, regulate intrinsic neuronal excitability. Here we discuss which aspects circuit function are under control, how this homeostasis realized on molecular levels, pathological consequences when impaired. A remaining challenge elucidate diverse cooperate within complex circuits enable them both flexible stable.

Language: Английский

Citations

19
Shedding light on cholecystokinin’s role in hippocampal neuroplasticity and memory formation DOI
Muhammad Asim, Huajie Wang, Xi Chen

et al.

Neuroscience & Biobehavioral Reviews, Journal Year: 2024, Volume and Issue: 159, P. 105615 - 105615

Published: March 2, 2024

Language: Английский

Citations

9
The times they are a-changin’: a proposal on how brain flexibility goes beyond the obvious to include the concepts of “upward” and “downward” to neuroplasticity DOI Creative Commons
Cassiano R.A.F. Diniz, Ana Paula Crestani

Molecular Psychiatry, Journal Year: 2022, Volume and Issue: 28(3), P. 977 - 992

Published: Dec. 27, 2022

Abstract Since the brain was found to be somehow flexible, plastic, researchers worldwide have been trying comprehend its fundamentals better understand itself, make predictions, disentangle neurobiology of diseases, and finally propose up-to-date treatments. Neuroplasticity is simple as a concept, but extremely complex when it comes mechanisms. This review aims bring light an aspect about neuroplasticity that often not given enough attention should, fact brain’s ability change would include disconnect synapses. So, neuronal shrinkage, decrease in spine density or dendritic complexity should included within concept part mechanisms, impairment it. To end, we extensively describe variety studies involving topics such neurodevelopment, aging, stress, memory homeostatic plasticity highlight how weakening disconnection synapses organically permeate so many ways good practice intrinsic physiology. Therefore, break down into two sub-concepts, “upward neuroplasticity” for changes related synaptic construction “downward deconstruction. With these could understood from bigger landscape vector which both directions taken flexibly adapt certain demands. Such paradigm shift allow understanding avoid any data interpretation bias, once makes clear there no morality with regard organic physiological involve dynamic biological systems seen brain.

Language: Английский

Citations

28
Age-related dysregulation of homeostatic control in neuronal microcircuits DOI Creative Commons
Carola I. Radulescu,

Nazanin Doostdar,

Nawal Zabouri

et al.

Nature Neuroscience, Journal Year: 2023, Volume and Issue: 26(12), P. 2158 - 2170

Published: Nov. 2, 2023

Neuronal homeostasis prevents hyperactivity and hypoactivity. Age-related suggests may be dysregulated in later life. However, plasticity mechanisms preventing age-related their efficacy life are unclear. We identify the adult cortical response to elevated activity driven by sensory overstimulation, then test how changes with age. use vivo two-photon imaging of calcium-mediated cellular/synaptic activity, electrophysiology c-Fos-activity tagging show control neuronal is visual cortex late adulthood. Specifically, young cortex, mGluR5-dependent population-wide excitatory synaptic weakening inhibitory synaptogenesis reduce following overstimulation. In life, these downregulated, so that overstimulation results strengthening activity. also find disrupts cognition older but not younger animals. propose specific fail dysregulating microcircuit can impact cognitive performance.

Language: Английский

Citations

19
Offline ensemble co-reactivation links memories across days DOI Creative Commons
Yosif Zaki, Zachary T. Pennington, Denisse Morales-Rodriguez

et al.

Nature, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 6, 2024

Abstract Memories are encoded in neural ensembles during learning 1–6 and stabilized by post-learning reactivation 7–17 . Integrating recent experiences into existing memories ensures that contain the most recently available information, but how brain accomplishes this critical process remains unclear. Here we show mice, a strong aversive experience drives offline ensemble of not only memory also neutral formed 2 days before, linking fear to previous memory. Fear specifically links retrospectively, prospectively, across days. Consistent with studies, find is reactivated period after learning. However, increases co-reactivation period. Ensemble occurs more wake than sleep. Finally, expression context associated shared between memories. Collectively, these results demonstrate mechanism which integrated

Language: Английский

Citations

7
Developmental Regulation of Homeostatic Plasticity in Mouse Primary Visual Cortex DOI Creative Commons
Wei Wen, Gina G. Turrigiano

Journal of Neuroscience, Journal Year: 2021, Volume and Issue: 41(48), P. 9891 - 9905

Published: Oct. 22, 2021

Homeostatic plasticity maintains network stability by adjusting excitation, inhibition, or the intrinsic excitability of neurons, but developmental regulation and coordination these distinct forms homeostatic remains poorly understood. A major contributor to this information gap is lack a uniform paradigm for chronically manipulating activity at different stages. To overcome limitation, we used designer receptors exclusively activated drugs (DREADDs) directly suppress neuronal in layer2/3 (L2/3) mouse primary visual cortex either sex two important timepoints: classic system critical period [CP; postnatal day 24 (P24) P29], adulthood (P45 P55). We show that h DREADD-mediated suppression simultaneously induces excitatory synaptic scaling up L2/3 pyramidal neurons during CP, consistent with previous observations using prolonged deprivation. Importantly, manipulations known block when induced pharmacologically via deprivation also prevented DREADD-induced plasticity. next same adult animals. Surprisingly, while persisted into adulthood, was completely absent. Finally, found changes quantal inhibitory input onto were absent CP present adults. Thus, population can express sets mechanisms development Our findings suggest be recruited modular manner according evolving needs developing neural circuit. SIGNIFICANCE STATEMENT Developing brain circuits are subject dramatic inputs could destabilize if left uncompensated. This compensation achieved through set provide slow, negative feedback adjustments excitability. Given very destabilizing forces stages, must tuned needs. Here developed method induce comparable windows juvenile mature engage strikingly

Language: Английский

Citations

39
Cholecystokinin B receptor antagonists for the treatment of depression via blocking long-term potentiation in the basolateral amygdala DOI
Xu Zhang, Muhammad Asim, Wei Fang

et al.

Molecular Psychiatry, Journal Year: 2023, Volume and Issue: 28(8), P. 3459 - 3474

Published: June 26, 2023

Language: Английский

Citations

12
Learning enhances representations of taste-guided decisions in the mouse gustatory insular cortex DOI Creative Commons
Joshua F. Kogan, Alfredo Fontanini

Current Biology, Journal Year: 2024, Volume and Issue: 34(9), P. 1880 - 1892.e5

Published: April 16, 2024

Learning to discriminate overlapping gustatory stimuli that predict distinct outcomes—a feat known as discrimination learning—can mean the difference between ingesting a poison or nutritive meal. Despite obvious importance of this process, very little is about neural basis taste learning. In other sensory modalities, form learning can be mediated by either sharpening representations enhanced ability "decision-making" circuits interpret information. Given dual role insular cortex (GC) in encoding both and decision-related variables, region represents an ideal site for investigating how activity changes animals learn novel discrimination. Here, we present results from experiments relying on two-photon calcium imaging GC mice performing taste-guided mixture task. The task allows recording before after induced training increasingly similar pairs mixtures. Single-neuron population analyses show time-varying pattern activity, with early responses emerging delivery binary, choice-encoding later delay decision made. Our demonstrate that, while information encoded context task, improved performance are associated specific enhancement responses.

Language: Английский

Citations

4