Biology subjects

Salar, S.

Publications and source records attributed to Salar, S..

3 recordsLinked to original sources

bioRxiv2026

KCC2 Activation Reverses Neurophysiological and Behavioral Deficits in Female Rett Mice

Rett syndrome is an X-linked neurodevelopmental disorder resulting from mutations in the MeCP2 gene, leading to intellectual disability, impaired motor coordination, decreased sociability, and seizures. Central to the underlying pathophysiology are deficits in synaptic inhibition, which are mediated by hyperpolarizing GABAAR currents. These events develop postnatally and are dependent upon increased neuronal Cl- extrusion mediated by SLC12A5 (KCC2). Therefore, we tested whether its activation modifies the disease phenotypes evident in female MeCP2+/- mice, using OV350, a direct activator of KCC2. OV350 rapidly induced a sustained reduction in EEG power, accompanied by a decrease in the severity of epileptic discharges. Increased motor coordination, sociability, and spatial memory were also observed. Deficits in KCC2 phosphorylation were also seen in MeCP2+/- mice, consistent with reductions in its activity that were also ameliorated by OV350. Thus, KCC2 activation may be efficacious in limiting the impact of Rett syndrome and other neurodevelopmental disorders.

neuroscience↗

bioRxiv2025

Neuroactive steroids activate membrane progesterone receptors to induce sex specific effects on protein kinase activity

Neuroactive steroids (NAS), which are synthesized in the brain from progesterone, exert potent effects on behavior and are used to treat postpartum depression, yet how these compounds induce sustained modifications in neuronal activity are ill-defined. Here, we examined the efficacy of NAS for membrane progesterone receptors (mPRs) {delta} and {varepsilon}, members of a family of GPCRs for progestins that are expressed in the CNS. NAS increase PKC activity via Gq activation of mPR{delta} with EC50s between 3-11nM. In contrast, they activate Gs via mPR{varepsilon} to potentiate PKA activity with similar potencies. NAS also induced rapid internalization of only mPR{delta}. In the forebrain of female mice, mPR{delta} expression levels were 8-fold higher than males. Consistent with this, activation of PKC by NAS was evident in acute brain slices from female mice. Collectively, our results suggests that NAS may exert sex-specific effects on intracellular signaling in the brain via activation of mPRs.

neuroscience↗

bioRxiv2022

Status epilepticus induces chronic silencing of burster and dominance of regular firing neurons during sharp wave-ripples in the mouse subiculum

Sharp wave-ripples (SWRs) are hippocampal oscillations associated with memory consolidation. The subiculum, as the hippocampal output structure, ensures that hippocampal memory representations are transferred correctly to the consolidating neocortical regions. Because patients with temporal lobe epilepsy often develop memory deficits, we hypothesized that epileptic networks may disrupt subicular SWRs. We therefore investigated the impact of experimentally induced status epilepticus (SE) on subicular SWRs and contributing pyramidal neurons using electrophysiological recordings in mouse hippocampal slices. Subicular SWRs expressed hyperexcitable features post-SE, including increased ripple and unit activity. While regular firing neurons normally remain silent during SWRs, selective disinhibition recruited more regular firing neurons for action potential generation during SWRs post-SE. By contrast, burster neurons generated fewer action potential bursts during SWRs post-SE. Furthermore, altered timing of postsynaptic and action potentials suggested distorted neuronal recruitment during SWRs. Distorted subicular SWRs may therefore impair information processing and memory consolidation in epilepsy.

neuroscience↗