scholarly journals Homeostatic plasticity and burst activity are mediated by hyperpolarization-activated cation currents and T-type calcium channels in neuronal cultures

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Anikó Rátkai ◽  
Krisztián Tárnok ◽  
Hajar El Aouad ◽  
Brigitta Micska ◽  
Katalin Schlett ◽  
...  
Keyword(s):  
Calcium Channels ◽  
Hippocampal Neurons ◽  
Pyramidal Neurons ◽  
Homeostatic Plasticity ◽  
Neuronal Cultures ◽  
Ca Channel ◽  
Homeostatic Regulation ◽  
Elevated Expression ◽  
Organotypic Slice Cultures ◽  
Hcn1 Channels

AbstractHomeostatic plasticity stabilizes neuronal networks by adjusting the responsiveness of neurons according to their global activity and the intensity of the synaptic inputs. We investigated the homeostatic regulation of hyperpolarization-activated cyclic nucleotide-gated (HCN) and T-type calcium (CaV3) channels in dissociated and organotypic slice cultures. After 48 h blocking of neuronal activity by tetrodotoxin (TTX), our patch-clamp experiments revealed an increase in the depolarizing voltage sag and post-inhibitory rebound mediated by HCN and CaV3 channels, respectively. All HCN subunits (HCN1 to 4) and T-type Ca-channel subunits (CaV3.1, 3.2 and 3.3) were expressed in both control and activity-deprived hippocampal cultures. Elevated expression levels of CaV3.1 mRNA and a selective increase in the expression of TRIP8b exon 4 isoforms, known to regulate HCN channel localization, were also detected in TTX-treated cultured hippocampal neurons. Immunohistochemical staining in TTX-treated organotypic slices verified a more proximal translocation of HCN1 channels in CA1 pyramidal neurons. Computational modeling also implied that HCN and T-type calcium channels have important role in the regulation of synchronized bursting evoked by previous activity-deprivation. Thus, our findings indicate that HCN and T-type Ca-channels contribute to the homeostatic regulation of excitability and integrative properties of hippocampal neurons.

Temporal Regulation of the Expression Locus of Homeostatic Plasticity

2006 ◽  
Vol 96 (4) ◽  
pp. 2127-2133 ◽  
Author(s):  
Corette J. Wierenga ◽  
Michael F. Walsh ◽  
Gina G. Turrigiano
Keyword(s):  
Hippocampal Neurons ◽  
Pyramidal Neurons ◽  
Homeostatic Plasticity ◽  
Excitatory Synapses ◽  
Postsynaptic Response ◽  
Network Function ◽  
Cortical Cultures ◽  
Mepsc Frequency ◽  
Visual Cortical

Homeostatic plasticity of excitatory synapses plays an important role in stabilizing neuronal activity, but the mechanism of this form of plasticity is incompletely understood. In particular, whether the locus of expression is presynaptic or postsynaptic has been controversial. Here we show that the expression locus depends on the time neurons have spent in vitro. In visual cortical cultures ≤14 days in vitro (DIV), 2 days of TTX treatment induced an increase in miniature excitatory postsynaptic current (mEPSC) amplitude onto pyramidal neurons, without affecting mEPSC frequency. However, in cultures ≥18 DIV, the same TTX treatment induced a large increase in mEPSC frequency, whereas the amplitude effect was reduced. The increased mEPSC frequency was associated with an increased density of excitatory synapses and increased presynaptic vesicle release in response to electrical stimulation. This indicates a shift from a predominantly postsynaptic response to TTX in ≤14 DIV cultures, to a coordinated pre- and postsynaptic response in ≥18 DIV cultures. This shift was not specific for cortical cultures because a similar shift was observed in cultured hippocampal neurons. Culturing neurons from older animals showed that the timing of the switch depends on the time the neurons have spent in vitro, rather than their postnatal age. This temporal switch in expression locus can largely reconcile the contradictory literature on the expression locus of homeostatic excitatory synaptic plasticity in central neurons. Furthermore, our results raise the intriguing possibility that the expression mechanism of homeostatic plasticity can be tailored to the needs of the network during different stages of development or in response to different challenges to network function.

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.

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.

Differential modulation of single voltage-gated calcium channels by cholinergic and adrenergic agonists in adult hippocampal neurons

1990 ◽  
Vol 64 (4) ◽  
pp. 1291-1302 ◽  
Author(s):  
R. Fisher ◽  
D. Johnston
Keyword(s):  
Calcium Channels ◽  
Hippocampal Neurons ◽  
Pyramidal Neurons ◽  
Single Channel ◽  
Mossy Fiber ◽  
Long Term Potentiation ◽  
High Threshold ◽  
Voltage Gated ◽  
Voltage Gated Calcium Channels ◽  
Ca3 Pyramidal Neurons

1. Pharmacologic agents known to modulate long-term potentiation (LTP) at the mossy fiber-to-CA3 pyramidal neuron synapse were tested for their effects on the activity of single voltage-gated calcium channels in adult CA3 pyramidal neurons. 2. Single-channel current recordings of three types of voltage-gated calcium channels were made from acutely exposed CA3 pyramidal neurons of the adult guinea pig hippocampus. 3. The beta-adrenergic agonist isoproterenol (10 microM), which is known to enhance LTP, increased the activity of the two high-threshold calcium channels (N and L) with no striking effect on the low-threshold (T) channel. 4. The muscarinic agonists carbachol and muscarine (1-10 microM), the latter of which has been shown to inhibit LTP, decreased the probability of opening of L channels, increased the probability of opening of T channels, and had no effect on N channels. The effects were blocked by 0.1 microM atropine. 5. These results are consistent with the hypothesis that neuromodulation of mossy fiber LTP occurs, at least in part, through the modulation of postsynaptic, voltage-gated calcium channels.

scholarly journals Epipregnanolone as a Positive Modulator of GABAA Receptor in Rat Cerebellar and Hippocampus Neurons

Biomolecules ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 791
Author(s):  
Julia Bukanova ◽  
Elena Solntseva ◽  
Rodion Kondratenko ◽  
Eva Kudova
Keyword(s):  
Gabaa Receptor ◽  
Purkinje Cells ◽  
Hippocampal Neurons ◽  
Pyramidal Neurons ◽  
Patch Clamp Technique ◽  
Dual Effect ◽  
Combined Application ◽  
Gabaa Receptor Antagonist ◽  
Positive Modulator ◽  
Endogenous Steroid

Epipregnanolone (3β-hydroxy-5β-pregnan-20-one, Epi) is an endogenous steroid with important physiological effects and high affinity for GABAA receptors. The effect of Epi on GABA-induced chloride current (IGABA) in native neurons has hardly been studied. In this work, we studied the influence of Epi on the IGABA in the Purkinje cells of rat cerebellum and pyramidal neurons of rat hippocampus with the patch clamp technique. We showed that Epi is a positive modulator of the IGABA with EC50 of 5.7 µM in Purkinje cells and 9.3 µM in hippocampal neurons. Epi-induced potentiation of the IGABA was more potent at low vs. high GABA concentrations. Isopregnanolone (3β-hydroxy-5α-pregnan-20-one, Iso) counteracted Epi, reducing its potentiating effect by 2–2.3 times. Flumazenil, a nonsteroidal GABAA receptor antagonist, does not affect the Epi-induced potentiation. Comparison of the potentiating effects of Epi and allopregnanolone (3α-hydroxy-5α-pregnan-20-one, ALLO) showed that ALLO is, at least, a four times more potent positive modulator than Epi. The combined application of ALLO and Epi showed that the effects of these two steroids are not additive. We conclude that Epi has a dual effect on the IGABA increasing the current in the control solution and decreasing the stimulatory effect of ALLO.

scholarly journals N-methyl-D-aspartate receptor-induced proteolytic conversion of postsynaptic class C L-type calcium channels in hippocampal neurons.

1996 ◽  
Vol 93 (8) ◽  
pp. 3362-3367 ◽  
Author(s):  
J. W. Hell ◽  
R. E. Westenbroek ◽  
L. J. Breeze ◽  
K. K. Wang ◽  
C. Chavkin ◽  
...  
Keyword(s):  
Calcium Channels ◽  
Hippocampal Neurons ◽  
Aspartate Receptor ◽  
Class C
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