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Moghimyfiroozabad, S.

Publications and source records attributed to Moghimyfiroozabad, S..

3 recordsLinked to original sources

A molecularly-defined non-redundant subpopulation of OPCs controls the generation of myelinating oligodendrocytes during postnatal development.

Oligodendrocyte precursor cells (OPCs) are a class of glial cells that uniformly tiles the whole central nervous system. They play several key functions across the brain including the generation of oligodendrocytes and the control of myelination. Whether the functional diversity of OPCs is the result of genetically defined subpopulations or of their regulation by external factors has not been definitely established. We discovered that a subpopulation of OPCs found across the brain is defined by the expression of C1ql1, a gene previously described for its synaptic function in neurons. This subpopulation starts to appear during the first postnatal week in the mouse brain. Ablation of C1ql1-expressing OPCs in the mouse is not compensated by the remaining OPCs, and results in a massive lack of oligodendrocytes and myelination in many brain regions. Therefore, C1ql1 is a molecular marker of a functionally non-redundant subpopulation of OPCs, which controls the generation of myelinating oligodendrocytes.

neuroscience↗

Mapping and targeting of C1ql1-expressing cells in the mouse

The C1Q complement protein C1QL1 is highly conserved in mammals where it is expressed in various tissues including the brain. This secreted protein interacts with Brain-specific Angiogenesis Inhibitor 3, BAI3/ADGRB3, and controls synapse formation and maintenance. C1ql1 is expressed in the inferior olivary neurons that send projections to cerebellar Purkinje cells, but its expression in the rest of the brain is less documented. To map C1ql1 expression and enable the specific targeting of C1ql1-expressing cells, we characterized a knockin mouse model expressing the Cre recombinase under the control of C1ql1 regulatory sequences. We characterized the capacity for Cre-driven recombination in the brain and mapped Cre expression in various neuron types using reporter mouse lines. Using an intersectional strategy with viral particle injections, we show that this mouse line can be used to target specific afferents of Purkinje cells. As C1ql1 is also expressed in other regions of the brain, as well as in other tissues such as adrenal glands, placenta, colon and testis, our mouse model is a useful tool to target C1ql1-expressing cells in a broad variety of tissues.

neuroscience↗

Two types of slow waves in anesthetized and sleeping brains

Sleep slow waves are known to participate in memory consolidation, yet slow waves occurring under anesthesia present no positive effects on memory. Here, we shed light onto this paradox, based on a combination of extracellular recordings in vivo, in vitro, and computational models. We find two types of slow waves, based on analyzing the temporal patterns of successive slow-wave events. The first type is consistently observed in natural slow-wave sleep, while the second is shown to be ubiquitous under anesthesia. Network models of spiking neurons predict that the two slow wave types emerge due to a different gain on inhibitory vs excitatory cells and that different levels of spike-frequency adaptation in excitatory cells can account for dynamical distinctions between the two types. This prediction was tested in vitro by varying adaptation strength using an agonist of acetylcholine receptors, which demonstrated a neuromodulatory switch between the two types of slow waves. Finally, we show that the first type of slow-wave dynamics is more sensitive to external stimuli, which can explain how slow waves in sleep and anesthesia differentially affect memory consolidation, as well as provide a link between slow-wave dynamics and memory diseases.

neuroscience↗