Biology subjects

Kovalchuk, Y.

Publications and source records attributed to Kovalchuk, Y..

5 recordsLinked to original sources

bioRxiv2025

Glomerulus-specific inhomogeneity of the basal activity map in the olfactory bulb supports olfactory-driven behavior

Glomeruli are signal-processing units of the olfactory bulb (OB), playing a key role in many OB computations, including contrast enhancement, gain control, and odorant-selective habituation. In awake mice, we uncover an extremely stable inhomogeneous map of basal glomerulus-specific activity as a background against which olfactory signal processing is performed. This activity is strongly driven by (i) centrifugal cholinergic projections, (ii) endogenous, and (iii) airflow-evoked spiking of olfactory sensory neurons and, to a small extent, (iv) by the odor environment. Importantly, early olfactory impairment in a mouse model of Alzheimers disease is parallelled by the loss of glomerular map inhomogeneity and diminished cholinergic innervation. These results reveal an important layer in the signal-processing network of the OB, likely acting by increasing the variance in and dynamic range of the system via glomerulus-specific functional inhomogeneity. TeaserA new layer in the signal-processing network of the olfactory bulb supports olfactory-driven behavior.

neuroscience↗

bioRxiv2024

Morphotype-specific calcium signaling in human microglia

Key functions of Ca2+ signaling in rodent microglia include monitoring the brain state or the surrounding neuronal activity and sensing the danger or damage in their vicinity. Microglial Ca2+ dyshomeostasis is a disease hallmark in many mouse models of neurological disorders but the Ca2+ signal properties of human microglia remain unknown. Using a newly developed toolbox, we analyzed in situ Ca2+ signaling of decades-old human cortical microglia. The data revealed marked compartmentalization of Ca2+ signals, with signal properties differing across the compartments and resident morphotypes. The basal Ca2+ levels were low in ramified and high in ameboid microglia. The fraction of cells with ongoing Ca2+ signaling, the fraction and the amplitude of process Ca2+ signals and the duration of somatic Ca2+ signals decreased when moving from ramified via hypertrophic to ameboid microglia. In contrast, the size of active compartments, the fraction and amplitude of somatic Ca2+ signals and the duration of process Ca2+ signals increased along this pathway.

immunology↗

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↗