The Electrophysiological Properties of Cortical Neurons in the Epileptic Foci of Children with Refractory Temporal Lobe Epilepsy

Malkin, Sergey L.; Khachatryan, V.; Fedorov, E. V.; Zaitsev, Aleksey V.

doi:10.1134/s0022093022010197

Cited by 3 publications

(1 citation statement)

References 42 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Passive and active membrane properties were investigated using neuronal responses to current steps (1.5 s duration every 3.5 s, amplitudes from -100 to +600 pA in 10-20 pA increments) as previously described [71]. Signals were recorded with the Heka EPC8 amplifier, digitized at 50 kHz frequency using the LIH 8+8 AD-DA converter and PatchMaster software (all from HEKA Elektronik GmbH, Germany).…”

Section: Slice Preparation and Electrophysiological Recordingsmentioning

confidence: 99%

Morphological and Functional Alterations in the CA1 Pyramidal Neurons of the Rat Hippocampus in the Chronic Phase of the Lithium-Pilocarpine Model of Epilepsy

Postnikova,

Diespirov,

Malkin

et al. 2024

Preprint

View full text Add to dashboard Cite

Epilepsy is known to cause alterations in neural networks. However, many details of these changes remain poorly understood. The objective of this study was to investigate changes in the properties of hippocampal CA1 pyramidal neurons and their synaptic inputs in a rat lithium-pilocarpine model of epilepsy. In the chronic phase of the model, we found a marked loss of pyramidal neurons in the CA1 area. However, the membrane properties of the neurons remained essentially unal-tered. The results of the electrophysiological and morphological studies indicate that the direct pathway from the entorhinal cortex to CA1 neurons is reinforced in epileptic animals, whereas the inputs to them from CA3 are either unaltered or even diminished. In particular, the dendritic spine density in the str. lacunosum moleculare, where the direct pathway from the entorhinal cortex ter-minates, was found to be 2.5 times higher in epileptic rats than in control rats. Furthermore, the summation of responses upon stimulation of the temporoammonic pathway was enhanced by approximately twofold in epileptic rats. This enhancement is believed to be a significant con-tributing factor to the heightened epileptic activity observed in the entorhinal cortex of epileptic rats using an ex vivo 4-aminopyridine model.

show abstract

Section: Slice Preparation and Electrophysiological Recordingsmentioning

confidence: 99%

Morphological and Functional Alterations in the CA1 Pyramidal Neurons of the Rat Hippocampus in the Chronic Phase of the Lithium-Pilocarpine Model of Epilepsy

Postnikova,

Diespirov,

Malkin

et al. 2024

Preprint

View full text Add to dashboard Cite

show abstract

Heterogeneity of synaptic NMDA receptor responses within individual lamina I pain‐processing neurons across sex in rats and humans

Dedek,

Topcu,

Dedek

et al. 2024

The Journal of Physiology

View full text Add to dashboard Cite

Excitatory glutamatergic NMDA receptors (NMDARs) are key regulators of spinal pain processing, and yet the biophysical properties of NMDARs in dorsal horn nociceptive neurons remain poorly understood. Despite the clinical implications, it is unknown whether the molecular and functional properties of synaptic NMDAR responses are conserved between males and females or translate from rodents to humans. To address these translational gaps, we systematically compared individual and averaged excitatory synaptic responses from lamina I pain‐processing neurons of adult Sprague–Dawley rats and human organ donors, including both sexes. By combining patch‐clamp recordings of outward miniature excitatory postsynaptic currents with non‐biased data analyses, we uncovered a wide range of decay constants of excitatory synaptic events within individual lamina I neurons. Decay constants of synaptic responses were distributed in a continuum from 1–20 ms to greater than 1000 ms, suggesting that individual lamina I neurons contain AMPA receptor (AMPAR)‐only as well as GluN2A‐, GluN2B‐ and GluN2D‐NMDAR‐dominated synaptic events. This intraneuronal heterogeneity in AMPAR‐ and NMDAR‐mediated decay kinetics was observed across sex and species. However, we discovered an increased relative contribution of GluN2A‐dominated NMDAR responses at human lamina I synapses compared with rodent synapses, suggesting a species difference relevant to NMDAR subunit‐targeting therapeutic approaches. The conserved heterogeneity in decay rates of excitatory synaptic events within individual lamina I pain‐processing neurons may enable synapse‐specific forms of plasticity and sensory integration within dorsal horn nociceptive networks. imageKey points Synaptic NMDA receptors (NMDARs) in spinal dorsal horn nociceptive neurons are key regulators of pain processing, but it is unknown whether their functional properties are conserved between males and females or translate from rodents to humans. In this study, we compared individual excitatory synaptic responses from lamina I pain‐processing neurons of male and female adult Sprague–Dawley rats and human organ donors. Individual lamina I neurons from male and female rats and humans contain AMPA receptor‐only as well as GluN2A, GluN2B‐ and GluN2D‐NMDAR‐dominated synaptic events. This may enable synapse‐specific forms of plasticity and sensory integration within dorsal horn nociceptive networks. Human lamina I synapses have an increased relative contribution of GluN2A‐dominated NMDAR responses compared with rodent synapses. These results uncover a species difference relevant to NMDAR subunit‐targeting therapeutic approaches.

show abstract

Morphological and Functional Alterations in the CA1 Pyramidal Neurons of the Rat Hippocampus in the Chronic Phase of the Lithium–Pilocarpine Model of Epilepsy

Postnikova,

Diespirov,

Malkin

et al. 2024

IJMS

View full text Add to dashboard Cite

Epilepsy is known to cause alterations in neural networks. However, many details of these changes remain poorly understood. The objective of this study was to investigate changes in the properties of hippocampal CA1 pyramidal neurons and their synaptic inputs in a rat lithium–pilocarpine model of epilepsy. In the chronic phase of the model, we found a marked loss of pyramidal neurons in the CA1 area. However, the membrane properties of the neurons remained essentially unaltered. The results of the electrophysiological and morphological studies indicate that the direct pathway from the entorhinal cortex to CA1 neurons is reinforced in epileptic animals, whereas the inputs to them from CA3 are either unaltered or even diminished. In particular, the dendritic spine density in the str. lacunosum moleculare, where the direct pathway from the entorhinal cortex terminates, was found to be 2.5 times higher in epileptic rats than in control rats. Furthermore, the summation of responses upon stimulation of the temporoammonic pathway was enhanced by approximately twofold in epileptic rats. This enhancement is believed to be a significant contributing factor to the heightened epileptic activity observed in the entorhinal cortex of epileptic rats using an ex vivo 4-aminopyridine model.

show abstract

The Electrophysiological Properties of Cortical Neurons in the Epileptic Foci of Children with Refractory Temporal Lobe Epilepsy

Cited by 3 publications

References 42 publications

Morphological and Functional Alterations in the CA1 Pyramidal Neurons of the Rat Hippocampus in the Chronic Phase of the Lithium-Pilocarpine Model of Epilepsy

Morphological and Functional Alterations in the CA1 Pyramidal Neurons of the Rat Hippocampus in the Chronic Phase of the Lithium-Pilocarpine Model of Epilepsy

Heterogeneity of synaptic NMDA receptor responses within individual lamina I pain‐processing neurons across sex in rats and humans

Morphological and Functional Alterations in the CA1 Pyramidal Neurons of the Rat Hippocampus in the Chronic Phase of the Lithium–Pilocarpine Model of Epilepsy

Contact Info

Product

Resources

About