Biology subjects

Jedrzejewska-Szmek, J.

Publications and source records attributed to Jedrzejewska-Szmek, J..

5 recordsLinked to original sources

bioRxiv2026

Calmodulin controls spatial and temporal specificity of calcium-induced calcium release

Calcium dynamics controls learning and memory, and abnormal calcium dynamics have been implicated in neurodegenerative disorders, such as Alzheimers disease (AD). Calcium dynamics are influenced by calcium-induced calcium release (CICR), which is mediated by ryanodine receptors (RyR) located on endoplasmic reticulum (ER) membrane. Calmodulin, one of the most abundant proteins in the brain, inhibits RyR2, expressed in the dendrites of hippocampal CA1 neurons, with several reported consequences: relief of this inhibition is responsible for heart failure, and enhancing calmodulin to RyR binding [1] alleviates cell loss and AD-like neuronal hyperexcitability. To investigate the role of calmodulin in aging and AD, we built a sophisticated reaction-diffusion model of a dendritic branch with ER. We showed that relieving calmodulin inhibition of RyR2 increased spatial and temporal spread of calcium transients in the dendrite. This effect was also visible in a model of old age, where disinhibition of half of the RyR2 population increased spatial spread of calcium transients by a factor of 2, and disinhibition of RyR2 combined with increased concentration of calcium buffering molecules increased duration of calcium transients. Lower activation of plasma membrane calcium ATPase (PMCA), which is also activated by calmodulin and inhibited by {beta}-Amyloid oligomers, and not RyR2 disinhibition, led to an increase in resting intracellular calcium concentration as observed in AD. Overall, our research demonstrates that changes in calmodulin that are associated with AD and aging, by regulation of RyR2 (in old age) and PMCA (in AD), underlie changes in calcium dynamics that might have consequences for learning and memory. Author summaryCalcium dynamics controls learning and memory. In neurons calcium dynamics are regulated by a complex system including calcium-permeable channels and extrusion pumps. The components of this system are regulated by calmodulin, which is enriched in the brain. We show that relieving calmodulin inhibition of calcium permeable channels, which accompanies aging, decreases spatial and temporal specificity of calcium release, contributing to the deficits in learning and memory observed in old age. In contrast, calcium extrusion pumps that are activated by calmodulin are likely responsible for increased resting intracellular calcium concentration observed in Alzheimers disease. In consequence, a novel role emerges for calmodulin, which in the brain is primarily considered a fast-acting calcium buffering molecule, as an important regulator in neuronal calcium dynamics underlying pathology.

neuroscience↗

bioRxiv2021

Social learning about rewards: how information from others helps to adapt to changing environment

Being a part of a social structure is key for survival and reproduction. Living with conspecifics boosts evolutionary fitness, by providing essential information about the environment. Nonetheless, studying neural mechanisms of social learning has not yet been established under laboratory conditions. To examine how socially passed information about the reward affects the behavior of individuals we used Eco-HAB, an automated system for tracing voluntary behavior of group-housed mice living under semi-naturalistic conditions. We show that a scent of a rewarded individual has profound effects on the conspecifics ability to find the reward in both familiar and novel environments. Importantly, the animals display clear and stable individual differences in social behavior. As a result, socially conveyed information has different effects on individual mice. Further, we show that disrupting neuronal plasticity in the prelimbic cortex with nanoparticles gradually releasing TIMP metallopeptidase inhibitor 1, disrupts animals social behavior and results in decreased ability to adapt to environmental changes. The experimental paradigm we developed can be further used to study neuronal mechanisms of social learning.

neuroscience↗

bioRxiv2020

What we can and what we cannot see with extracellular multielectrodes

Extracellular recording is an accessible technique used in animals and humans to study the brain physiology and pathology. As the number of recording channels and their density grows it is natural to ask how much improvement the additional channels bring in and how we can optimally use the new capabilities for monitoring the brain. Here we show that for any given distribution of electrodes we can establish exactly what information about current sources in the brain can be recovered and what information is strictly unobservable. We demonstrate this in the general setting of previously proposed kernel Current Source Density method and illustrate it with simplified examples as well as using evoked potentials from the barrel cortex obtained with a Neuropixels probe and with compatible model data. Author SummaryEvery set of measurements is a window into reality rendering its incomplete or distorted picture. It is often difficult to relate the obtained representation of the world to underlying ground truth. Here we show, for brain electrophysiology, for arbitrary experimental setup (distribution of electrodes), and arbitrary analytical setup (function space of current source densities), that one can identify distributions of current sources which can be recovered precisely, and those which are invisible in the system. This shows what is and what is not observable in the studied system for a given setup, allows to improve the analysis results by modifying analytical setup, and facilitates interpretation of the measured sets of LFP, ECoG and EEG recordings.

neuroscience↗

bioRxiv2020

c-Fos-MMP-9 pathway in central amygdala mediates approach motivation but not reward consumption

Although impaired motivational and consummatory aspects of reward behavior are core symptoms of several psychiatric disorders, the underlying neural and molecular mechanisms remain poorly understood. c-Fos, as a component of AP-1 transcription factor, regulates the expression of matrix metalloproteinase 9 (MMP-9), an enzyme involved in synaptic remodeling and plasticity. Both proteins are expressed in the central amygdala (CeA) that orchestrates appetitive and aversive responses. We have examined the role of c-Fos and MMP-9 in CeA in reward and punishment processing. We have manipulated c-Fos and MMP-9 levels in vivo using: RNAi-based approach to block c-Fos expression, inhibitor-releasing nanoparticles to block MMP-9 activity, and lentiviral vector to increase MMP-9 expression. To assess motivation, consumption and learning reinforced by either a sweet or bitter-tasting solution, we employed automated behavioral tests in the IntelliCage cystem. We have used transgenic mouse lines to identify CeA cells expressing c-Fos and a specific fluorescently labelled substrate peptide to measure MMP-9 activity. Excitability of neurons was measured with patch-clamp. Blocking c-Fos expression has been found to disrupt both reward processing components, motivational and consummatory, while inhibition of MMP-9 activity has impaired only motivational aspects of the behavior. On the other hand, punishment processing has not been affected by those manipulations. Furthermore, we have observed that reward training induces c-Fos expression in both somatostatin (SST)+, and SST-neurons, while MMP-9 activity is increased in SST- subpopulation only. We have further linked SST+ population to consummatory reactions by showing that reward consumption increases excitability of the SST+ neurons. These findings reveal molecular mechanisms of motivational anhedonia, linking it to c-Fos-MMP-9 pathway and CeA SST- neurons, and consummatory anhedonia, linking it to c-Fos and CeA SST+ neurons.

neuroscience↗

bioRxiv2019

kCSD-python, a tool for reliable Current Source Density estimation

Interpretation of the extracellular recordings can be difficult due to the long range of electric field but can be facilitated by estimating the density of current sources (CSD). Here we introduce kCSD-python, an open Python package implementing Kernel Current Source Density (kCSD) method, and introduce several new techniques to facilitate CSD analysis of experimental data and interpretation of the results. We investigate the limitations imposed by noise and assumptions in the method itself. kCSD-python allows CSD estimation for arbitrary distribution of electrodes in 1D, 2D, and 3D, assuming distributions of sources in tissue, a slice, or in a single cell, and includes a range of diagnostic aids. We demonstrate its features in a Jupyter notebook tutorial to facilitate uptake by the community.

neuroscience↗