scholarly journals Multiple shared mechanisms for homeostatic plasticity in rodent somatosensory and visual cortex

2017 ◽  
Vol 372 (1715) ◽  
pp. 20160157 ◽  
Author(s):  
Melanie A. Gainey ◽  
Daniel E. Feldman
Keyword(s):  
Visual Cortex ◽  
Sensory Deprivation ◽  
Homeostatic Plasticity ◽  
Intrinsic Excitability ◽  
Synaptic Scaling ◽  
Cellular Mechanisms ◽  
Firing Rates ◽  
Parvalbumin Interneuron ◽  
Activity Dependent ◽  
V1 Cortex

We compare the circuit and cellular mechanisms for homeostatic plasticity that have been discovered in rodent somatosensory (S1) and visual (V1) cortex. Both areas use similar mechanisms to restore mean firing rate after sensory deprivation. Two time scales of homeostasis are evident, with distinct mechanisms. Slow homeostasis occurs over several days, and is mediated by homeostatic synaptic scaling in excitatory networks and, in some cases, homeostatic adjustment of pyramidal cell intrinsic excitability. Fast homeostasis occurs within less than 1 day, and is mediated by rapid disinhibition, implemented by activity-dependent plasticity in parvalbumin interneuron circuits. These processes interact with Hebbian synaptic plasticity to maintain cortical firing rates during learned adjustments in sensory representations. This article is part of the themed issue ‘Integrating Hebbian and homeostatic plasticity’.

scholarly journals Developmental Regulation of Homeostatic Plasticity in Mouse Primary Visual Cortex

2021 ◽  
Author(s):  
Wei Wen ◽  
Gina Turrigiano
Keyword(s):  
Visual Cortex ◽  
Primary Visual Cortex ◽  
Pyramidal Neurons ◽  
Neural Circuit ◽  
Developmental Regulation ◽  
Visual Deprivation ◽  
Homeostatic Plasticity ◽  
Designer Drugs ◽  
Inhibitory Input ◽  
Synaptic Scaling

Homeostatic plasticity maintains network stability by adjusting excitation, inhibition, or the intrinsic excitability of neurons, but the developmental regulation and coordination of these distinct forms of homeostatic plasticity remains poorly understood. A major contributor to this information gap is the lack of a uniform paradigm for chronically manipulating activity at different developmental stages. To overcome this limitation, we utilized Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) to directly suppress neuronal activity in layer (L) 2/3 of mouse primary visual cortex (V1) at two important developmental timepoints: the classic visual system critical period (CP, P24-29), and adulthood (P45-55). We show that 24 hours of DREADD-mediated activity suppression simultaneously induces excitatory synaptic scaling up and intrinsic homeostatic plasticity in L2/3 pyramidal neurons during the CP, consistent with previous observations using prolonged visual deprivation. Importantly, manipulations known to block these forms of homeostatic plasticity when induced pharmacologically or via visual deprivation also prevented DREADD-induced homeostatic plasticity. We next used the same paradigm to suppress activity in adult animals. Surprisingly, while excitatory synaptic scaling persisted into adulthood, intrinsic homeostatic plasticity was completely absent. Finally, we found that homeostatic changes in quantal inhibitory input onto L2/3 pyramidal neurons were absent during the CP but present in adults. Thus, the same population of neurons can express distinct sets of homeostatic plasticity mechanisms at different development stages. Our findings suggest that homeostatic forms of plasticity can be recruited in a modular manner according to the evolving needs of a developing neural circuit.

scholarly journals Activity-dependent synaptic GRIP1 accumulation drives synaptic scaling up in response to action potential blockade

2015 ◽  
Vol 112 (27) ◽  
pp. E3590-E3599 ◽  
Author(s):  
Melanie A. Gainey ◽  
Vedakumar Tatavarty ◽  
Marc Nahmani ◽  
Heather Lin ◽  
Gina G. Turrigiano
Keyword(s):  
Action Potential ◽  
Ampa Receptors ◽  
Scaling Up ◽  
Receptor Trafficking ◽  
Neuronal Firing ◽  
Homeostatic Plasticity ◽  
Synaptic Scaling ◽  
Interacting Protein ◽  
Excitatory Postsynaptic Currents ◽  
Activity Dependent

Synaptic scaling is a form of homeostatic plasticity that stabilizes neuronal firing in response to changes in synapse number and strength. Scaling up in response to action-potential blockade is accomplished through increased synaptic accumulation of GluA2-containing AMPA receptors (AMPAR), but the receptor trafficking steps that drive this process remain largely obscure. Here, we show that the AMPAR-binding protein glutamate receptor-interacting protein-1 (GRIP1) is essential for regulated synaptic AMPAR accumulation during scaling up. Synaptic abundance of GRIP1 was enhanced by activity deprivation, directly increasing synaptic GRIP1 abundance through overexpression increased the amplitude of AMPA miniature excitatory postsynaptic currents (mEPSCs), and shRNA-mediated GRIP1 knockdown prevented scaling up of AMPA mEPSCs. Furthermore, knockdown and replace experiments targeting either GRIP1 or GluA2 revealed that scaling up requires the interaction between GRIP1 and GluA2. Finally, GRIP1 synaptic accumulation during scaling up did not require GluA2 binding. Taken together, our data support a model in which activity-dependent trafficking of GRIP1 to synaptic sites drives the forward trafficking and enhanced synaptic accumulation of GluA2-containing AMPAR during synaptic scaling up.

scholarly journals BDNF Regulates the Intrinsic Excitability of Cortical Neurons

1999 ◽  
Vol 6 (3) ◽  
pp. 284-291
Author(s):  
Niraj S. Desai ◽  
Lana C. Rutherford ◽  
Gina G. Turrigiano
Keyword(s):  
Cortical Neurons ◽  
Neuronal Excitability ◽  
Pyramidal Neurons ◽  
Homeostatic Plasticity ◽  
Intrinsic Excitability ◽  
Intrinsic Properties ◽  
General Role ◽  
Outward Currents ◽  
Visual Cortical ◽  
Activity Dependent

Neocortical pyramidal neurons respond to prolonged activity blockade by modulating their balance of inward and outward currents to become more sensitive to synaptic input, possibly as a means of homeostatically regulating firing rates during periods of intense change in synapse number or strength. Here we show that this activity-dependent regulation of intrinsic excitability depends on the neurotrophin brain-derived neurotrophic factor (BDNF). In experiments on rat visual cortical cultures, we found that exogenous BDNF prevented, and a TrkB–IgG fusion protein reproduced, the change in pyramidal neuron excitability produced by activity blockade. Most of these effects were also observed in bipolar interneurons, indicating a very general role for BDNF in regulating neuronal excitability. Moreover, earlier work has demonstrated that BDNF mediates a different kind of homeostatic plasticity present in these same cultures: scaling of the quantal amplitude of AMPA-mediated synaptic inputs up or down as a function of activity. Taken together, these results suggest that BDNF may be the signal controlling a coordinated regulation of synaptic and intrinsic properties aimed at allowing cortical networks to adapt to long-lasting changes in activity.

scholarly journals Nonreciprocal homeostatic compensation in Drosophila potassium channel mutants

2017 ◽  
Vol 117 (6) ◽  
pp. 2125-2136 ◽  
Author(s):  
Eugene Z. Kim ◽  
Julie Vienne ◽  
Michael Rosbash ◽  
Leslie C. Griffith
Keyword(s):  
Motor Neurons ◽  
Transcriptional Response ◽  
External Input ◽  
Homeostatic Plasticity ◽  
Intrinsic Excitability ◽  
Channel Conductance ◽  
The Face ◽  
Activity Dependent ◽  
Homeostatic Response

Homeostatic control of intrinsic excitability is important for long-term regulation of neuronal activity. In conjunction with many other forms of plasticity, intrinsic homeostasis helps neurons maintain stable activity regimes in the face of external input variability and destabilizing genetic mutations. In this study, we report a mechanism by which Drosophila melanogaster larval motor neurons stabilize hyperactivity induced by the loss of the delayed rectifying K+ channel Shaker cognate B ( Shab), by upregulating the Ca2+-dependent K+ channel encoded by the slowpoke ( slo) gene. We also show that loss of SLO does not trigger a reciprocal compensatory upregulation of SHAB, implying that homeostatic signaling pathways utilize compensatory pathways unique to the channel that was mutated. SLO upregulation due to loss of SHAB involves nuclear Ca2+ signaling and dCREB, suggesting that the slo homeostatic response is transcriptionally mediated. Examination of the changes in gene expression induced by these mutations suggests that there is not a generic transcriptional response to increased excitability in motor neurons, but that homeostatic compensations are influenced by the identity of the lost conductance. NEW & NOTEWORTHY The idea that activity-dependent homeostatic plasticity is driven solely by firing has wide credence. In this report we show that homeostatic compensation after loss of an ion channel conductance is tailored to identity of the channel lost, not its properties.

scholarly journals Activity-dependent tuning of intrinsic excitability in mouse and human neurogliaform cells

2020 ◽  
Author(s):  
R. Chittajallu ◽  
K. Auville ◽  
V. Mahadevan ◽  
M. Lai ◽  
S. Hunt ◽  
...  
Keyword(s):  
Cognitive Processing ◽  
Intrinsic Excitability ◽  
Inhibitory Influence ◽  
Essential Property ◽  
Normal Brain ◽  
Cellular Mechanisms ◽  
Normal Brain Function ◽  
Circuit Function ◽  
And Behavior ◽  
Activity Dependent

ABSTRACTThe ability to modulate the efficacy of synaptic communication between neurons constitutes an essential property critical for normal brain function. Animal models have proved invaluable in revealing a wealth of diverse cellular mechanisms underlying varied plasticity modes. However, to what extent these processes are mirrored in humans is largely uncharted thus questioning their relevance to human circuit function. In this study, we focus on neurogliaform cells, a specialized form of neuron that possess physiological features enabling them to impart a widespread inhibitory influence on neural activity. We demonstrate that this prominent neuronal subtype, embedded in both mouse and human neural circuits, undergo remarkably similar activity-dependent modulation manifesting as epochs of enhanced intrinsic excitability. In principle, these evolutionary conserved plasticity routes likely tune the extent of neurogliaform cell mediated inhibition thus constituting canonical circuit mechanisms relevant for human cognitive processing and behavior.

scholarly journals Kv1.1 contributes to a rapid homeostatic plasticity of intrinsic excitability in CA1 pyramidal neurons in vivo

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Peter James Morgan ◽  
Romain Bourboulou ◽  
Caroline Filippi ◽  
Julie Koenig-Gambini ◽  
Jérôme Epsztein
Keyword(s):  
Pyramidal Neurons ◽  
Place Cells ◽  
Homeostatic Plasticity ◽  
Intrinsic Excitability ◽  
Memory Interference ◽  
Ca1 Pyramidal Neurons ◽  
Whole Cell Patch Clamp ◽  
Activity Dependent

In area CA1 of the hippocampus, the selection of place cells to represent a new environment is biased towards neurons with higher excitability. However, different environments are represented by orthogonal cell ensembles, suggesting that regulatory mechanisms exist. Activity-dependent plasticity of intrinsic excitability, as observed in vitro, is an attractive candidate. Here, using whole-cell patch-clamp recordings of CA1 pyramidal neurons in anesthetized rats, we have examined how inducing theta-bursts of action potentials affects their intrinsic excitability over time. We observed a long-lasting, homeostatic depression of intrinsic excitability which commenced within minutes, and, in contrast to in vitro observations, was not mediated by dendritic Ih. Instead, it was attenuated by the Kv1.1 channel blocker dendrotoxin K, suggesting an axonal origin. Analysis of place cells’ out-of-field firing in mice navigating in virtual reality further revealed an experience-dependent reduction consistent with decreased excitability. We propose that this mechanism could reduce memory interference.

scholarly journals Response to short-term deprivation of the human adult visual cortex measured with 7T BOLD

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Paola Binda ◽  
Jan W Kurzawski ◽  
Claudia Lunghi ◽  
Laura Biagi ◽  
Michela Tosetti ◽  
...  
Keyword(s):  
Visual Cortex ◽  
Frequency Tuning ◽  
Sensory Deprivation ◽  
Ocular Dominance ◽  
Monocular Deprivation ◽  
Homeostatic Plasticity ◽  
Short Term ◽  
Structural Reorganization ◽  
Parvocellular Pathway ◽  
Human Adult

Sensory deprivation during the post-natal ‘critical period’ leads to structural reorganization of the developing visual cortex. In adulthood, the visual cortex retains some flexibility and adapts to sensory deprivation. Here we show that short-term (2 hr) monocular deprivation in adult humans boosts the BOLD response to the deprived eye, changing ocular dominance of V1 vertices, consistent with homeostatic plasticity. The boost is strongest in V1, present in V2, V3 and V4 but absent in V3a and hMT+. Assessment of spatial frequency tuning in V1 by a population Receptive-Field technique shows that deprivation primarily boosts high spatial frequencies, consistent with a primary involvement of the parvocellular pathway. Crucially, the V1 deprivation effect correlates across participants with the perceptual increase of the deprived eye dominance assessed with binocular rivalry, suggesting a common origin. Our results demonstrate that visual cortex, particularly the ventral pathway, retains a high potential for homeostatic plasticity in the human adult.

scholarly journals A Bidirectional Switch in the Shank3 Phosphorylation State Biases Synapses toward Up or Down Scaling

2021 ◽  
Author(s):  
Gina G Turrigiano ◽  
Chi-Hong Wu ◽  
Vedakumar Tatavarty ◽  
Pierre M Jean-Beltran ◽  
Andrea Guerrero ◽  
...  
Keyword(s):  
Posttranslational Modifications ◽  
Scaling Up ◽  
Homeostatic Plasticity ◽  
Synaptic Scaling ◽  
Synaptic Localization ◽  
Neocortical Neurons ◽  
Associated Proteins ◽  
Scaling Down ◽  
Activity Dependent

Homeostatic synaptic plasticity requires widespread remodeling of synaptic signaling and scaffolding networks, but the role of posttranslational modifications in this process has not been systematically studied. Using deepscale, quantitative analysis of the phosphoproteome in mouse neocortical neurons, we found wide-spread and temporally complex changes during synaptic scaling up and down. We observed 424 bidirectionally modulated phosphosites that were strongly enriched for synapse-associated proteins, including S1539 in the ASD-associated synaptic scaffold protein Shank3. Using a parallel proteomic analysis performed on Shank3 isolated from rat neocortical neurons by immunoaffinity, we identified two sites that were hypo-phosphorylated during scaling up and hyper-phosphorylated during scaling down: one (rat S1615) that corresponded to S1539 in mouse, and a second highly conserved site, rat S1586. The phosphorylation status of these sites modified the synaptic localization of Shank3 during scaling protocols, and dephosphorylation of these sites via PP2A activity was essential for the maintenance of synaptic scaling up. Finally, phosphomimetic mutations at these sites prevented scaling up but not down, while phosphodeficient mutations prevented scaling down but not up. Thus, an activity-dependent switch between hypo- and hyperphosphorylation at S1586/ S1615 of Shank3 enables scaling up or down, respectively. Collectively our data show that activity-dependent phosphoproteome dynamics are important for the functional reconfiguration of synaptic scaffolds, and can bias synapses toward upward or downward homeostatic plasticity.

scholarly journals Synaptic Scaling and Homeostatic Plasticity in the Mouse Visual Cortex In Vivo

Neuron ◽  
2013 ◽  
Vol 80 (2) ◽  
pp. 327-334 ◽  
Author(s):  
Tara Keck ◽  
Georg B. Keller ◽  
R. Irene Jacobsen ◽  
Ulf T. Eysel ◽  
Tobias Bonhoeffer ◽  
...  
Keyword(s):  
Visual Cortex ◽  
Homeostatic Plasticity ◽  
Synaptic Scaling ◽  
Mouse Visual Cortex

scholarly journals Activity-dependent tuning of intrinsic excitability in mouse and human neurogliaform cells

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Ramesh Chittajallu ◽  
Kurt Auville ◽  
Vivek Mahadevan ◽  
Mandy Lai ◽  
Steven Hunt ◽  
...  
Keyword(s):  
Cognitive Processing ◽  
Intrinsic Excitability ◽  
Inhibitory Influence ◽  
Essential Property ◽  
Normal Brain ◽  
Cellular Mechanisms ◽  
Normal Brain Function ◽  
Circuit Function ◽  
And Behavior ◽  
Activity Dependent

The ability to modulate the efficacy of synaptic communication between neurons constitutes an essential property critical for normal brain function. Animal models have proved invaluable in revealing a wealth of diverse cellular mechanisms underlying varied plasticity modes. However, to what extent these processes are mirrored in humans is largely uncharted thus questioning their relevance in human circuit function. In this study, we focus on neurogliaform cells, that possess specialized physiological features enabling them to impart a widespread inhibitory influence on neural activity. We demonstrate that this prominent neuronal subtype, embedded in both mouse and human neural circuits, undergo remarkably similar activity-dependent modulation manifesting as epochs of enhanced intrinsic excitability. In principle, these evolutionary conserved plasticity routes likely tune the extent of neurogliaform cell mediated inhibition thus constituting canonical circuit mechanisms underlying human cognitive processing and behavior.

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