Biology subjects

Mojtahedi, N.

Publications and source records attributed to Mojtahedi, N..

4 recordsLinked to original sources

bioRxiv2025

Early postnatal CA3 hyperexcitability drives hippocampal development and epileptogenesis in SCN2A developmental and epileptic encephalopathy

Developmental and epileptic encephalopathies caused by pathogenic variants in SCN2A (SCN2A-DEE), encoding the voltage-gated sodium channel Nav1.2, present with early-life seizures, developmental delay, and increased mortality. Using a novel Scn2a p.A263V gain-of-function (GOF) mouse model, we demonstrate gene-dose and background-dependent phenotypes ranging from self-limited neonatal seizures to chronic epilepsy with high mortality. In vivo electrophysiology revealed hippocampal seizures as early as postnatal day 2.5, with CA3-driven gamma oscillations preceding seizure onset. CA3 and CA1 pyramidal neurons exhibited transient hyperexcitability during early postnatal development, resolving by P24-30. Single-cell RNA sequencing uncovered gene dose-dependent accelerated maturation of hippocampal networks, peaking at P7, alongside widespread transcriptional changes in excitatory and inhibitory neurons. In adulthood, persistent hippocampal network alterations emerged, marked by reduced mid-gamma oscillations and theta-gamma coupling. Our findings establish hippocampal CA3 hyperexcitability as an early driver of epileptogenesis in SCN2A-DEE and highlight it as a potential therapeutic target to mitigate disease progression.

neuroscience↗

bioRxiv2021

Patterned endogenous activity controls migration, morphogenesis and survival of adult-born neurons in the mouse olfactory bulb

The development and survival of adult-born neurons is believed to be driven by sensory signaling. By genetically manipulating excitability of adult-born cells (via cell-specific overexpression of either Kv1.2 or Kir2.1 K+ channels), longitudinal in vivo monitoring of their Ca2+ signaling and transcriptome analyses, we show that endogenous but not sensory-driven activity governs migration, morphogenesis, survival, and functional integration of adult-born juxtaglomerular neurons in the mouse olfactory bulb. The proper development of these cells required fluctuations of cytosolic Ca2+ levels, phosphorylation of CREB, and pCREB-mediated gene expression. Attenuating Ca2+ fluctuations via K+ channel overexpression strongly downregulated genes involved in neuronal migration, differentiation, and morphogenesis and upregulated apoptosis-related genes, thus locking adult-born cells in the vulnerable and immature state. Together, the data reveal signaling pathways connecting the endogenous intermittent neuronal activity/Ca2+ fluctuations as well as proper Kv1.2/Kir2.1 K+ channel function to migration, maturation, and survival of adult-born neurons.

neuroscience↗

bioRxiv2021

Stable behavioral state-specific large scale activity patterns in the developing cortex of neonates

Endogenous neuronal activity is a hallmark of the developing brain. In rodents, a handful of such activities were described in different cortical areas but the unifying macroscopic perspective is still lacking. Here we combined large-scale in vivo Ca2+ imaging of the dorsal cortex in non-anesthetized neonatal mice with advanced mathematical analyses to reveal unique behavioral state-specific maps of endogenous activity. These maps were remarkably stable over time within and across experiments and used patches of correlated activity with little hemispheric symmetry as well as stationary and propagating waves as building blocks. Importantly, the maps recorded during motion and rest were almost inverse, with sensory-motor areas active during motion and posterior-lateral areas active at rest. The retrosplenial cortex engaged in both resting- and motion-related activities, building functional long-range connections with respective cortical areas. The data obtained bind different region-specific activity patterns described so far into a single consistent picture and set the stage for future inactivation studies, probing the exact function of this complex activity pattern for cortical wiring in neonates.

neuroscience↗

bioRxiv2020

Enhanced ongoing endogenous activity predicts elimination of adult-born neurons in the mouse olfactory bulb

Adult-born cells, arriving daily into the rodent olfactory bulb, either integrate into the neural circuitry or get eliminated. Whether these two populations differ in their morphological or functional properties remains, however, unclear. Using longitudinal in vivo two-photon imaging, we monitored dendritic morphogenesis, odor-evoked responsiveness, endogenous Ca2+ signaling, and survival/death of adult-born juxtaglomerular neurons (abJGNs). We found that maturation of abJGNs is accompanied by a significant reduction in dendritic complexity, with surviving and subsequently eliminated cells showing similar degrees of dendritic remodeling. Surprisingly, 63% of eliminated abJGNs acquired odor-responsiveness before death, with amplitudes and time courses of odor-evoked responses similar to those recorded in surviving cells. We observed, however, a significant long-lasting enhancement of endogenous Ca2+ signaling in subsequently eliminated abJGNs, visible already 6 days before death. These findings identify ongoing endogenous Ca2+ signaling as a key predictor of abJGNs fate.

neuroscience↗