Homeostatic regulation of axonal Kv1.1 channels accounts for both synaptic and intrinsic modifications in the hippocampal CA3 circuit

2021 ◽  
Vol 118 (47) ◽  
pp. e2110601118
Author(s):  
Mickaël Zbili ◽  
Sylvain Rama ◽  
Maria-José Benitez ◽  
Laure Fronzaroli-Molinieres ◽  
Andrzej Bialowas ◽  
...  
Keyword(s):  
Synaptic Transmission ◽  
Pyramidal Neurons ◽  
Homeostatic Plasticity ◽  
Intrinsic Excitability ◽  
Homeostatic Regulation ◽  
Major Mechanism ◽  
Hippocampal Ca3 ◽  
Synaptic Receptors ◽  
Intrinsic Plasticity ◽  
Immunohistochemical Techniques

Homeostatic plasticity of intrinsic excitability goes hand in hand with homeostatic plasticity of synaptic transmission. However, the mechanisms linking the two forms of homeostatic regulation have not been identified so far. Using electrophysiological, imaging, and immunohistochemical techniques, we show here that blockade of excitatory synaptic receptors for 2 to 3 d induces an up-regulation of both synaptic transmission at CA3–CA3 connections and intrinsic excitability of CA3 pyramidal neurons. Intrinsic plasticity was found to be mediated by a reduction of Kv1.1 channel density at the axon initial segment. In activity-deprived circuits, CA3–CA3 synapses were found to express a high release probability, an insensitivity to dendrotoxin, and a lack of depolarization-induced presynaptic facilitation, indicating a reduction in presynaptic Kv1.1 function. Further support for the down-regulation of axonal Kv1.1 channels in activity-deprived neurons was the broadening of action potentials measured in the axon. We conclude that regulation of the axonal Kv1.1 channel constitutes a major mechanism linking intrinsic excitability and synaptic strength that accounts for the functional synergy existing between homeostatic regulation of intrinsic excitability and synaptic transmission.

scholarly journals Homeostatic regulation of axonal Kv1.1 channels accounts for both synaptic and intrinsic modifications in CA3 circuit

2021 ◽  
Author(s):  
Mickaël Zbili ◽  
Sylvain Rama ◽  
Maria-José Benitez ◽  
Laure Fronzaroli-Molinieres ◽  
Andrzej Bialowas ◽  
...  
Keyword(s):  
Synaptic Transmission ◽  
Pyramidal Neurons ◽  
Synaptic Strength ◽  
Homeostatic Plasticity ◽  
Intrinsic Excitability ◽  
Homeostatic Regulation ◽  
Synaptic Receptors ◽  
Immunohistochemical Techniques ◽  
Unique Mechanism ◽  
Presynaptic Facilitation

AbstractHomeostatic plasticity of intrinsic excitability goes hand-in-hand with homeostatic plasticity of synaptic transmission. However, the mechanisms linking the two forms of homeostatic regulation have not been identified so far. Using electrophysiological, imaging and immunohistochemical techniques, we show here that blockade of excitatory synaptic receptors for 2-3 days induces an up-regulation of synaptic strength at CA3-CA3 connexions and intrinsic excitability of CA3 pyramidal neurons. Activity-deprived connexions were found to express a high release probability, an insensitivity to dendrotoxin, and a lack of depolarization-induced presynaptic facilitation, indicating a loss of presynaptic Kv1.1 function. The down-regulation of Kv1.1 channels in activity-deprived neurons was confirmed by their broader action potentials measured in the axon that were insensitive to dendrotoxin. We conclude that regulation of axonal Kv1.1 channel constitutes a unique mechanism linking intrinsic excitability and synaptic strength that accounts for the functional synergy existing between homeostatic regulation of intrinsic excitability and synaptic transmission.

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 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.

Reduced Synaptic and Intrinsic Excitability of a Subtype of Pyramidal Neurons in the Medial Prefrontal Cortex in a Mouse Model of Alzheimer’s Disease

2021 ◽  
pp. 1-12
Author(s):  
Xiao-Qin Zhang ◽  
Le Xu ◽  
Si-Yu Yang ◽  
Lin-Bo Hu ◽  
Fei-Yuan Dong ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Prefrontal Cortex ◽  
Synaptic Transmission ◽  
Pyramidal Neurons ◽  
Intrinsic Excitability ◽  
Rodent Models ◽  
Morphological Complexity ◽  
Sholl Analysis ◽  
Model Of Alzheimer’S Disease

Background: Abnormal morphology and function of neurons in the prefrontal cortex (PFC) are associated with cognitive deficits in rodent models of Alzheimer’s disease (AD), particularly in cortical layer-5 pyramidal neurons that integrate inputs from different sources and project outputs to cortical or subcortical structures. Pyramidal neurons in layer-5 of the PFC can be classified as two subtypes depending on the inducibility of prominent hyperpolarization-activated cation currents (h-current). However, the differences in the neurophysiological alterations between these two subtypes in rodent models of AD remain poorly understood. Objective: To investigate the neurophysiological alterations between two subtypes of pyramidal neurons in hAPP-J20 mice, a transgenic model for early onset AD. Methods: The synaptic transmission and intrinsic excitability of pyramidal neurons were investigated using whole-cell patch recordings. The morphological complexity of pyramidal neurons was detected by biocytin labelling and subsequent Sholl analysis. Results: We found reduced synaptic transmission and intrinsic excitability of the prominent h-current (PH) cells but not the non-PH cells in hAPP-J20 mice. Furthermore, the function of hyperpolarization-activated cyclic nucleotide-gated (HCN) channels which mediated h-current was disrupted in the PH cells of hAPP-J20 mice. Sholl analysis revealed that PH cells had less dendritic intersections in hAPP-J20 mice comparing to control mice, implying that a lower morphological complexity might contribute to the reduced neuronal activity. Conclusion: These results suggest that the PH cells in the medial PFC may be more vulnerable to degeneration in hAPP-J20 mice and play a sustainable role in frontal dysfunction in AD.

scholarly journals Topographic heterogeneity of intrinsic excitability in mouse hippocampal CA3 pyramidal neurons

2020 ◽  
Vol 124 (4) ◽  
pp. 1270-1284
Author(s):  
Qian Sun ◽  
Yu-Qiu Jiang ◽  
Melissa C. Lu
Keyword(s):  
Pyramidal Neurons ◽  
Intrinsic Excitability ◽  
Hippocampal Region ◽  
Topographic Organization ◽  
Hippocampal Ca3 ◽  
Ca3 Pyramidal Neurons ◽  
Episodic Memories ◽  
Topographic Heterogeneity ◽  
Area Ca3

Area CA3 is a major hippocampal region that is classically thought to act as a homogeneous neural network vital for spatial navigation and episodic memories. Here, we report that CA3 pyramidal neurons exhibit marked heterogeneity of somatodendritic morphology and cellular electrical properties along both proximodistal and dorsoventral axes. These new results uncover a complex, yet orderly, pattern of topographic organization of CA3 neuronal features that may contribute to its in vivo functional diversity.

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

2019 ◽  
Author(s):  
Peter James Morgan ◽  
Romain Bourboulou ◽  
Caroline Filippi ◽  
Julie Koenig-Gambini ◽  
Jérôme Epsztein
Keyword(s):  
Pyramidal Neurons ◽  
Homeostatic Plasticity ◽  
Author Response ◽  
Intrinsic Excitability ◽  
Ca1 Pyramidal Neurons
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