Biology subjects

Szuromi, M. P.

Publications and source records attributed to Szuromi, M. P..

3 recordsLinked to original sources

bioRxiv2026

Competing routes back to firing shape population hyperexcitability and its selective suppression

Whether a neuron will fire again is fundamentally a different question from whether a quiescent neuron will activate. Even within the same neuron, successive spikes can follow distinct post-spike trajectories, with after-depolarization permitting early return to firing and depolarization block prolonging inactivity. Therefore, we propose that hyperexcitability involves changes in the opportunities to fire again across the spike cycle, and not just from quiescence. The firing hazard makes these opportunities measurable: in whole-cell recordings of midbrain dopamine neurons, the subthreshold voltage trough resolves a non-monotone aggregate firing hazard into physiologically distinguishable components. We represent these components as competing return pathways within a population renewal model and show that they lead to heterogeneous firing patterns within a single neuronal population subject to a common drive. An immediate-return pathway provides an early opportunity to fire by skipping some stages of recovery, and promotes population hyperexcitability independent of quiescent activation. Conversely, a sequestration pathway diverts recently active neurons into a prolonged non-recruitable state, representing depolarization block or use-dependent blockade. Pharmacological selectivity of anti-seizure medications such as phenytoin and carbamazepine arises from the redistribution of neurons among return pathways at every renewal, with fast-cycling pathological regimes providing more opportunities for renewal and eventual sequestration.

neuroscience↗

bioRxiv2025

Dysfunction-specific Mechanisms Critically Influence Seizure Onset and Termination in Epilepsy

Epileptic seizures result from abnormal synchronous neuronal firing caused by an imbalance between excitatory and inhibitory neurotransmission. While most seizures are self-limiting, those lasting over five minutes, termed status epilepticus, require medical intervention. Benzodiazepines, the first-line treatment, terminate seizures by enhancing GABAergic inhibition, but fail in approximately 36% of cases. In this paper, we employ a neural mass framework to investigate how different interventions influence brain dynamics and facilitate seizure termination. As seizures are characterized by persistent firing, we extend the classic Wilson-Cowan framework by introducing a term called sustenance which encodes factors that promote or discourage perpetual firing. The resulting model captures transitions between normal activity and seizure and provides a tractable framework for analysing diverse pathophysiological mechanisms. We first show how various dysfunctions -- such as hyperexcitation, depletion of inhibitory neurotransmitters, and depolarizing GABAergic transmission -- can all give rise to seizures, with overlapping but distinct dynamics. Building on this foundation, we turn to the central question of intervention: how different treatments act on these mechanisms to terminate seizures. We find that while enhancing GABAergic inhibition is generally effective, it fails when GABA becomes depolarizing. In such cases, interventions like levetiracetam that suppress sustained excitatory activity remain effective. These findings highlight the importance of aligning interventions to the specific underlying dysfunction for effective seizure termination.

neuroscience↗

bioRxiv2023

Using compartmental models to understand excitation-inhibition imbalance in epilepsy

Epileptic seizures are characterized by abnormal synchronous bursting of neurons. This is commonly attributed to an imbalance between excitatory and inhibitory neurotransmission. We introduce compartmental models from epidemiology to study this interaction between excitatory and inhibitory populations of neurons in the context of epilepsy. Neurons could either be bursting or susceptible, and the propagation of action potentials within the brain through the bursting of neurons is considered as an infection spreading through a population. We model the recruitment of neurons into bursting and their subsequent decay to susceptibility to be influenced by the proportion of excitatory and inhibitory neurons bursting, resulting in a two population Susceptible - Infected - Susceptible (SIS) model. This approach provides a tractable framework to inspect the mechanisms behind seizure generation and termination. Considering the excitatory neurotransmission as an epidemic spreading through the neuronal population and the inhibitory neurotransmission as a competing epidemic that stops the spread of excitation, we establish the conditions for a seizure-like state to be stable. Subsequently, we show how an activity-dependent dysfunction of inhibitory mechanisms such as impaired GABAergic inhibition or inhibitory-inhibitory interactions could result in a seizure even when the above conditions are not satisfied.

neuroscience↗