Calcium-permeable AMPA receptors are essential to the synaptic plasticity induced by epileptiform activity in rat hippocampal slices

Postnikova, Tatyana Y.; Amakhin, Dmitry V.; Trofimova, Alina M.; Zaitsev, Aleksey V.

doi:10.1016/j.bbrc.2020.06.121

Cited by 16 publications

(19 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Although most mesial temporal lobe structures are highly susceptible to seizures, the hippocampal area demonstrates the heaviest damage in response to seizure activity [13,14]. Several mechanisms can provoke changes in the excitability of neuronal networks, including changes in intrinsic neuronal excitability [15][16][17], potentiation of excitatory synaptic contacts [9,[18][19][20][21], changes in synaptic inhibition [22][23][24][25], and cell loss and sprouting of axons [26][27][28]. However, relatively little is known about the precise mechanisms of the network excitability increase resulting from a brief episode of epileptic activity-what specific changes occur at presynaptic and postsynaptic levels, and how these changes affect hippocampal circuit functioning.…”

Section: Introductionmentioning

confidence: 99%

Short-Term Epileptiform Activity Potentiates Excitatory Synapses but Does Not Affect Intrinsic Membrane Properties of Pyramidal Neurons in the Rat Hippocampus In Vitro

et al. 2021

Self Cite

View full text Add to dashboard Cite

Even brief epileptic seizures can lead to activity-dependent structural remodeling of neural circuitry. Animal models show that the functional plasticity of synapses and changes in the intrinsic excitability of neurons can be crucial for epileptogenesis. However, the exact mechanisms underlying epileptogenesis remain unclear. We induced epileptiform activity in rat hippocampal slices for 15 min using a 4-aminopyridine (4-AP) in vitro model and observed hippocampal hyperexcitability for at least 1 hour. We tested several possible mechanisms of this hyperexcitability, including changes in intrinsic membrane properties of neurons and presynaptic and postsynaptic alterations. Neither input resistance nor other essential biophysical properties of hippocampal CA1 pyramidal neurons were affected by epileptiform activity. The glutamate release probability also remained unchanged, as the frequency of miniature EPSCs and the paired amplitude ratio of evoked responses did not change after epileptiform activity. However, we found an increase in the AMPA/NMDA ratio, suggesting alterations in the properties of postsynaptic glutamatergic receptors. Thus, the increase in excitability of hippocampal neural networks is realized through postsynaptic mechanisms. In contrast, the intrinsic membrane properties of neurons and the probability of glutamate release from presynaptic terminals are not affected in a 4-AP model.

show abstract

Section: Introductionmentioning

confidence: 99%

Short-Term Epileptiform Activity Potentiates Excitatory Synapses but Does Not Affect Intrinsic Membrane Properties of Pyramidal Neurons in the Rat Hippocampus In Vitro

et al. 2021

Self Cite

View full text Add to dashboard Cite

show abstract

“…Many researchers have reported the appearance of CP‐AMPARs at specific synapses during the induction of certain forms of synaptic plasticity, including long‐term potentiation (LTP) associates with memory consolidation, or following certain behavioural manipulations, such as fear conditioning 33,34 . These receptors have high conductance and enhance synaptic transmission, and they may activate unique Ca 2+ ‐sensitive signalling pathways related to LTP 35‐37 . The main difference between each of the AMPAR subunits is their C‐terminal sequences, and these determine their interaction with the differential scaffold protein.…”

Section: Discussionmentioning

confidence: 99%

“…33,34 These receptors have high conductance and enhance synaptic transmission, and they may activate unique Ca 2+ -sensitive signalling pathways related to LTP. [35][36][37] The main difference between each of the AMPAR subunits is their C-terminal sequences, and these determine their interaction with the differential scaffold protein. All AMPARs contain PDZ domains, which interact with different synaptic proteins.…”

Section: Discussionmentioning

confidence: 99%

HDACi protects against vascular cognitive impairment from CCH injury via induction of BDNF‐related AMPA receptor activation

Fang

Hsieh

Vidyanti

et al. 2021

J Cellular Molecular Medi

View full text Add to dashboard Cite

We previously showed a hydroxamic acid‐based histone deacetylase inhibitor (HDACi), compound 13, provides neuroprotection against chronic cerebral hypoperfusion (CCH) both in vitro under oxygen‐glucose deprivation (OGD) conditions and in vivo under bilateral common carotid artery occlusion (BCCAO) conditions. Intriguingly, the protective effect of this HDACi is via H3K14 or H4K5 acetylation–mediated differential BDNF isoform activation. BDNF is involved in cell proliferation and differentiation in development, synaptic plasticity and in learning and memory related with receptors or synaptic proteins. B6 mice underwent BCCAO and were randomized into 4 groups; a sham without BCCAO (sham), BCCAO mice injected with DMSO (DMSO), mice injected with HDACi‐compound 13 (compound 13) and mice injected with suberoylanilide hydroxamic acid (SAHA). The cortex and hippocampus of mice were harvested at 3 months after BCCAO, and levels of BDNF, AMPA receptor and dopamine receptors (D1, D2 and D3) were studied using Western blotting analysis or immunohistochemistry. We found that the AMPA receptor plays a key role in the molecular mechanism of this process by modulating HDAC. This protective effect of HDACi may be through BDNF; therefore, activation of this downstream signalling molecule, for example by AMPA receptors, could be a therapeutic target or intervention applied under CCH conditions.

show abstract

“…Synaptically connected excitatory glutamatergic neurons play critical roles in the abnormally synchronous discharges when epileptic seizures occur (Rogawski, 2013). Recent studies identified that CP-AMPARs may contribute to neural dysfunction and the related excitotoxicity in epilepsy (Shao et al, 2018;Konen et al, 2020;Postnikova et al, 2020).…”

Section: Epilepsy/seizuresmentioning

confidence: 99%

Calcium Permeable-AMPA Receptors and Excitotoxicity in Neurological Disorders

Guo

Yao

2021

Front. Neural Circuits

View full text Add to dashboard Cite

Excitotoxicity is one of the primary mechanisms of cell loss in a variety of diseases of the central and peripheral nervous systems. Other than the previously established signaling pathways of excitotoxicity, which depend on the excessive release of glutamate from axon terminals or over-activation of NMDA receptors (NMDARs), Ca2+ influx-triggered excitotoxicity through Ca2+-permeable (CP)-AMPA receptors (AMPARs) is detected in multiple disease models. In this review, both acute brain insults (e.g., brain trauma or spinal cord injury, ischemia) and chronic neurological disorders, including Epilepsy/Seizures, Huntington’s disease (HD), Parkinson’s disease (PD), Alzheimer’s disease (AD), amyotrophic lateral sclerosis (ALS), chronic pain, and glaucoma, are discussed regarding the CP-AMPAR-mediated excitotoxicity. Considering the low expression or absence of CP-AMPARs in most cells, specific manipulation of the CP-AMPARs might be a more plausible strategy to delay the onset and progression of pathological alterations with fewer side effects than blocking NMDARs.

show abstract

Calcium-permeable AMPA receptors are essential to the synaptic plasticity induced by epileptiform activity in rat hippocampal slices

Cited by 16 publications

References 43 publications

Short-Term Epileptiform Activity Potentiates Excitatory Synapses but Does Not Affect Intrinsic Membrane Properties of Pyramidal Neurons in the Rat Hippocampus In Vitro

Short-Term Epileptiform Activity Potentiates Excitatory Synapses but Does Not Affect Intrinsic Membrane Properties of Pyramidal Neurons in the Rat Hippocampus In Vitro

HDACi protects against vascular cognitive impairment from CCH injury via induction of BDNF‐related AMPA receptor activation

Calcium Permeable-AMPA Receptors and Excitotoxicity in Neurological Disorders

Contact Info

Product

Resources

About