Biology subjects

Nasretdinov, A.

Publications and source records attributed to Nasretdinov, A..

2 recordsLinked to original sources

bioRxiv2025

Dual role of Spreading Depolarization in the epileptic focus

Spreading Depolarizations (SDs) are often associated with epileptic discharges. While SDs are traditionally thought contributing to the postictal depression and termination of epileptic discharges, seizures may also occur during SDs or may even follow SDs suggesting that interactions between SD and seizures are more complex. Here, we examined the interactions between SD and epileptic activity by spatially separating the epileptic focus and the site of SD initiation. Epileptic focus was induced by local intracortical injection of the potassium channel blocker 4-AP combined with the GABA(A) receptor antagonist gabazine, whereas extrinsic SDs were evoked by distal high potassium application. We found that extrinsic SDs promoted seizure-like events (SLEs) when the SD wave approached the epileptic focus, followed by suppression of epileptic activity when SD spread through the focus. The timing of SLE relatively SD varied at different recordings sites, with SLEs occurring before, during or after SD arrival depending on electrode position along the trajectory of SD propagation between the SD initiation site and the epileptic focus. During intracortical recordings, the proconvulsive effects of SD were associated with a wave of pre-SD neuronal excitation reaching the epileptic focus. The epileptic focus per se also demonstrated a resistance to the SD invasion. Thus, the interactions between SD and epileptic focus are not limited to postictal depression, and SDs may also promote epileptic activity in the hyperexcitable cortex. Key pointsO_LIEffects of SD on epileptic focus are dual: both pro- and anticonvulsive C_LIO_LISDs promote epileptic discharges upon approaching the epileptic focus C_LIO_LIThe timing of epileptic discharges relatively SD varies along the SD trajectory C_LIO_LIProconvulsive effects of SD align with the pre-SD excitation C_LIO_LIEpileptic focus resists the SD propagation C_LI

neuroscience↗

bioRxiv2023

Excitatory neurons in stratum radiatum provide an alternative pathway for excitation flow that escapes perisomatic inhibition

For over half a century, it has been postulated that the internal excitatory circuit in the hippocampus consists of three relay stations. Excitation arrives from the entorhinal cortex to the DG granule cells, is transmitted through the mossy fibers to CA3 pyramidal cells, and is then transmitted through Schaffer collaterals to CA1 pyramidal neurons. In all three structures (DG, CA3 and CA1), the activity of the excitatory neurons involved in the synaptic transmission of excitation are under the control of inhibitory basket neurons that are recruited into network activity via feed-forward and feed-back excitation. However, in the late 90s "stratum radiatum giant cells" were described as a novel type of neuron with the anatomical features of excitatory cells. Since then, the role of these cells in the hippocampal circuitry has not been well understood. Here, using optogenetic and electrophysiological techniques we characterized the functional location of these neurons within the hippocampal network. We show that: (i) the main excitatory drive to giant excitatory neurons in stratum radiatum (ExNR) comes via Schaffer collaterals; (ii) within the CA1 field, ExNR are not directly connected with local pyramidal cells, but provide massive and efficient excitatory input to parvalbumin positive (PV+) interneurons; (iii) ExNR are reciprocally innervated by bistratified cells, but not inhibited by backet interneurons; (iv) the efficiency of ExNR excitation to PV+ interneurons is sufficient for a single ExNR action potential to trigger massive inhibition of downstream CA1 pyramidal cells. Taken together, our data shows that ExNR constitute an alternative pathway of excitation for CA1 interneurons that avoids the burden of perisomatic inhibition.

neuroscience↗