Degeneracy in epilepsy: multiple routes to hyperexcitable brain circuits and their repair

Communications Biology, Journal Year: 2023, Volume and Issue: 6(1)

Published: May 3, 2023

Abstract Due to its complex and multifaceted nature, developing effective treatments for epilepsy is still a major challenge. To deal with this complexity we introduce the concept of degeneracy field research: ability disparate elements cause an analogous function or malfunction. Here, review examples epilepsy-related at multiple levels brain organisation, ranging from cellular network systems level. Based on these insights, outline new multiscale population modelling approaches disentangle web interactions underlying design personalised multitarget therapies.

Language: Английский

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Editorial: Biologically inspired Artificial Intelligent systems: state and perspectives

Frontiers in Materials, Journal Year: 2025, Volume and Issue: 12

Published: Feb. 18, 2025

Language: Английский

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H‐current modulation of cortical Up and Down states

The Journal of Physiology, Journal Year: 2025, Volume and Issue: unknown

Published: March 28, 2025

Abstract Understanding the link between cellular processes and brain function remains a key challenge in neuroscience. One crucial aspect is interplay specific ion channels network dynamics. This work reveals role for h‐current, hyperpolarization‐activated cationic current, shaping cortical slow oscillations. Cortical oscillations are generated not only during wave sleep deep anaesthesia, but also association with disorders of consciousness lesions. exhibit rhythmic periods activity (Up states) alternating silent (Down states). By progressively reducing h‐current both slices computational model, we observed Up states transformed into prolonged plateaus sustained firing, while Down were significantly extended. transformation led to fivefold reduction oscillation frequency. In biophysical recurrent identified mechanisms underlying this dynamics: an increased neuronal input resistance membrane time constant, increasing responsiveness even weak inputs. A partial block therefore resulted change state. HCN (hyperpolarization‐activated cyclic nucleotide‐gated) channels, which generate known targets neuromodulation, suggesting potential pathways dynamic control rhythms. image Key points We investigated emergent dynamics, specifically states, slices. Blocking lasting up 4 s. elongated oscillatory frequency decreased. model replicated these findings allowed us explore mechanisms. An increase constant rise excitability, synaptic firing rates. Our results highlight significant controlling patterns, making it relevant target neuromodulators regulating states.

Language: Английский

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Genetic mechanisms for impaired synaptic plasticity in schizophrenia revealed by computational modeling

Proceedings of the National Academy of Sciences, Journal Year: 2024, Volume and Issue: 121(34)

Published: Aug. 14, 2024

Schizophrenia phenotypes are suggestive of impaired cortical plasticity in the disease, but mechanisms these deficits unknown. Genomic association studies have implicated a large number genes that regulate neuromodulation and plasticity, indicating genetic origin. Here, we used biochemically detailed computational modeling postsynaptic to investigate how schizophrenia-associated long-term potentiation (LTP) depression (LTD). We combined our model with data from postmortem RNA expression (CommonMind gene-expression datasets) assess consequences altered plasticity-regulating for amplitude LTP LTD. Our results show alterations observed post mortem, especially those anterior cingulate cortex, lead protein kinase A (PKA)-pathway-mediated synapses containing GluR1 receptors. validated findings using genotyped electroencephalogram (EEG) dataset where polygenic risk scores synaptic ion channel-encoding as well modulation visual evoked potentials were determined 286 healthy controls. provide possible mechanism impairments schizophrenia, which can improved understanding and, ultimately, treatment disorder.

Language: Английский

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Cannabidiol Modulates M-Type K+ and Hyperpolarization-Activated Cation Currents

Biomedicines, Journal Year: 2023, Volume and Issue: 11(10), P. 2651 - 2651

Published: Sept. 27, 2023

Cannabidiol (CBD) is a naturally occurring compound found in the Cannabis plant that known for its potential therapeutic effects. However, impact on membrane ionic currents remains topic of debate. This study aimed to investigate how CBD modifies various types pituitary GH3 cells. Results showed exposure led concentration-dependent decrease M-type K+ (IK(M)), with an IC50 3.6 μM, and caused quasi-steady-state activation curve current shift more depolarized no changes curve’s steepness. The CBD-mediated block IK(M) was not reversed by naloxone, suggesting it mediated opioid receptors. elicited pulse-train stimulation also decreased upon CBD. magnitude erg-mediated slightly reduced adding (10 μM), while density voltage-gated Na+ short depolarizing pulse affected it. Additionally, hyperpolarization-activated cation (Ih) 3.3 oxaliplatin. Ih shifted leftward direction slope factor curve. diminished strength voltage-dependent hysteresis upright isosceles-triangular ramp voltage. Collectively, these findings suggest CBD’s modification presented herein independent cannabinoid or receptors may exert significant functional activities excitable cells vitro vivo.

Language: Английский

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Modulating Hyperpolarization-Activated Cation Currents through Small Molecule Perturbations: Magnitude and Gating Control

Biomedicines, Journal Year: 2023, Volume and Issue: 11(8), P. 2177 - 2177

Published: Aug. 2, 2023

The hyperpolarization-activated cation current (Ih) exhibits a slowly activating time course of the when cell membrane is hyperpolarized for an extended duration. It involved in generating electrical activity various excitable cells. Numerous structurally distinct compounds or herbal drugs have potential to impact both magnitude and gating kinetics this current. Brivaracetam, chemical analog levetiracetam known be ligand synaptic vesicle protein 2A, could directly suppress Ih magnitude. Carisbamate, anticonvulsant agent, not only inhibited amplitude but also reduced strength voltage-dependent hysteresis (Hys(V)) associated with Ih. Cilobradine, similar ivabradine, Ih; however, it suppressed delayed-rectifier K+ currents. Dexmedetomidine, agonist α2-adrenergic receptor, exerted depressant action on concentration-dependent fashion. Suppression was observed GAL-021, breathing control modulator, present at concentration exceeding 30 μM. Lutein, one few xanthophyll carotenoids, able as well depress Hys(V)’s Pirfenidone, pyridine derivative anti-fibrotic depressed concentration- Tramadol, synthetic centrally active analgesic, shown reduce magnitude, independent its interaction opioid receptors. Various drugs, including ent-kaurane-type diterpenoids from Croton tonkinensis, Ganoderma triterpenoids, honokiol, pterostilbene, demonstrated efficacy reducing Conversely, oxaliplatin, platinum-based chemotherapeutic compound, effectively increase amplitude. Collectively, regulatory effects these cellular function can partly attributed their perturbations

Language: Английский

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Localization of hyperpolarization-activated cyclic nucleotide-gated channels in the vertebrate retinas across species and their physiological roles

Frontiers in Neuroanatomy, Journal Year: 2024, Volume and Issue: 18

Published: March 18, 2024

Transmembrane proteins known as hyperpolarization-activated cyclic nucleotide-gated (HCN) channels control the movement of Na + and K ions across cellular membranes. HCN are to be involved in crucial physiological functions regulating neuronal excitability rhythmicity, pacemaker activity heart. Although have been relatively well investigated brain, their distribution function retina received less attention, remaining roles comprehensively understood. Also, because recent studies reported somewhat linked with dysfunction photoreceptors which affected by retinal diseases, investigating may offer valuable insights into disease mechanisms potentially contribute identifying novel therapeutic targets for degenerative disorders. This paper endeavors summarize existing literature on vertebrate retinas various species discuss potential implications treatment diseases. Then, we recapitulate current knowledge regarding regulation channels, relevance neurological

Language: Английский

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The Cooperative Neuron

Oxford University Press eBooks, Journal Year: 2023, Volume and Issue: unknown

Published: April 20, 2023

Abstract The Cooperative Neuron roots our understanding of mental life, as consciously experienced and studied by psychologists, in recent discoveries cellular neurophysiology, which show that many neurons the mammalian neocortex have capabilities transcend those assumed twentieth-century psychology systems neuroscience. These receive information from other parts brain amplify their transmission when appropriate context. Amplification is defined quantified using advances theory contributions different inputs to can be distinguished. This context-sensitive cooperative style Big Data processing produces widespread coherence operations are localized within each a multitude local neuronal processors. book shows how this provides foundations for contextual disambiguation perception, selective attention, working memory imagery, emotional prioritization, cognitive control, learning, has profound implications neurobiology, psychology, neurology, psychiatry, philosophy. written wide audience, it explains neuroscience neuroscientists, both fields philosophers, students behavioural sciences, all intrigued enduring mystery brains minds. Finally, identifies issues inviting exploration.

Language: Английский

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H-current modulation of cortical Up and Down states

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: April 10, 2024

Abstract Understanding the link between cellular processes and brain function remains a key challenge in neuroscience. One crucial aspect is interplay specific ion channels network dynamics. This work reveals role for h-current, hyperpolarization-activated cationic current, shaping cortical slow oscillations. Cortical oscillations exhibit rhythmic periods of activity (Up states) alternating with silent (Down states). By progressively reducing h-current both slices computational model, we observed Up states transformed into prolonged plateaus sustained firing, while Down were also significantly extended. transformation led to five-fold reduction oscillation frequency. In biophysical recurrent identified mechanisms: an increased input resistance membrane time constant, increasing neuronal responsiveness even weak inputs. HCN channels, molecular basis are known neuromodulatory targets, suggesting potential pathways dynamic control rhythms.

Language: Английский

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Brain-like hardware, do we need it?

Frontiers in Neuroscience, Journal Year: 2024, Volume and Issue: 18

Published: Dec. 16, 2024

The brain's ability to perform efficient and fault-tolerant data processing is strongly related its peculiar interconnected adaptive architecture, based on redundant neural circuits interacting at different scales. By emulating the learning mechanisms, computing technologies strive achieve higher levels of energy efficiency computational performance. Although efforts address neuromorphic solutions through hardware top-down CMOS-based have obtained interesting results in terms energetic improvement, replication self-assembled architectures not considered roadmaps electronics. exploration elemental blocks mimic biological networks' complexity explored general frame unconventional it has reached yet a maturity stage enabling benchmark with standard electronic approaches performances, compatibility scalability. Here we discuss some aspects advantages disadvantages emulation brain for hardware. We also possible directions hybrid where substrates coexist integrate conventional electronics view architectures.

Language: Английский

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