Biology subjects

Ignatowska-Jankowska, B. M.

Publications and source records attributed to Ignatowska-Jankowska, B. M..

7 recordsLinked to original sources

bioRxiv2026

Motor experience leads to structural changes in the adult male mouse inferior olive

The activity of the inferior olive (IO), conveyed to the cerebellar cortex via climbing fibers and manifesting as the complex spikes (CSs) in Purkinje neurons, is at the core of major theories of cerebellar function and motor learning. While the computational meaning of the CSs remains under intense debate, it is well accepted that changes in their occurrence and timing play a critical role in guiding cerebellar plasticity. However, it has not been examined whether the plastic processes leading to these changes in cerebellar CS activity are expressed in the IO, or whether they are entirely caused by changes in brain structures upstream of the climbing fibers, including the cerebellar nuclei. Here, we examine whether prolonged, kinematically challenging motor experience can lead to detectable changes in the IO network structure that could underlie shifts in cerebellar CS activity. As the IO neurons communicate exclusively via electrical synapses (gap junctions) residing on dendritic structures, we hypothesized that if long-term increases in electrical coupling related to the insertion of new gap junctions occur in response to novel motor experiences, morphological changes in the dendrites would also be expected. To investigate this, we quantitatively characterized the geometry of the IO neuropil revealed by immunohistochemical staining in adult male mice. We found that the neuropil structure varies across olivary subnuclei in naive animals, possibly underlying known differences in cerebellar complex spike co-activation patterns. Geometrical measures related to structural complexity also revealed that exposing the animals to a challenging high-speed treadmill running task requiring full-body coordination led to localized changes suggestive of increased network connectivity. In addition, the density of immunofluorescence puncta labeling Cx36 increased in the same regions, supporting the notion that exposure to contexts where novel motor skills need to be acquired may lead to changes in the clustering strength among IO neurons and thereby restructuring of the olivo-cerebellar micromodules. To our knowledge, this is the first report of experience-related plasticity within the IO, calling for renewed attention to the role of the IO in olivocerebellar function.

neuroscience↗

bioRxiv2025

Repeated administration of cannabidiol decreases splenic lymphocyte numbers in rats: involvement of CB2 receptors

Cannabidiol (CBD), the major non-psychotropic compound of Cannabis sp., is an effective treatment for inflammatory and autoimmune diseases and produces various anti-tumor effects but the mechanisms of its long-term actions in vivo remain unclear. We have previously shown that CBD administration (5 mg/kg) in healthy rats significantly decreased lymphocyte numbers in peripheral blood, involving B, T CD4+ and T CD8+ lymphocyte subsets, but not natural killer (NK) cells. To examine the effects of CBD on lymphocyte subsets in the spleen and NK cellular cytotoxicity (NKCC), adult male Wistar rats (n = 63) were administered intraperitoneal injections of CBD (2.5 or 5 mg/kg/day) for 14 consecutive days and lymphocyte counts were obtained using flow cytometry. NKCC in the peripheral blood and spleen was quantified using a Chromium-51 release assay. Furthermore, CB2 receptors were blocked using selective receptor antagonist AM630 (1 mg/kg). The results indicate that repeated administration of CBD at a dose of 5 mg/kg/day resulted in a decrease in splenic lymphocyte number, involving T and B lymphocytes but not NK cells. The decrease in lymphocyte number was partially blocked by pretreatment with CB2 receptor antagonist while no changes in NKCC were observed following CBD administration. These results reveal that in healthy rats, CBD produces similar lymphopenic effects in the spleen as it does in peripheral blood and that the effects of CBD on lymphocyte numbers in vivo are at least partially mediated by CB2 receptors.

immunology↗

bioRxiv2024

Cannabinoid receptor 1 positive allosteric modulator ZCZ011 shows differential effects on behavior and the endocannabinoid system in HIV-1 Tat transgenic female and male mice

The cannabinoid receptor type 1 (CB1R) is a promising therapeutic target for various neurodegenerative diseases, including HIV-1-associated neurocognitive disorder (HAND). However, the therapeutic potential of CB1R by direct activation is limited due to its psychoactive side effects. Therefore, research has focused on indirectly activating the CB1R by utilizing positive allosteric modulators (PAMs). Studies have shown that CB1R PAMs (ZCZ011 and GAT211) are effective in mouse models of Huntingtons disease and neuropathic pain, and hence, we assess the therapeutic potential of ZCZ011 in a well-established mouse model of neuroHIV. The current study investigates the effect of chronic ZCZ011 treatment (14 days) on various behavioral paradigms and the endocannabinoid system in HIV-1 Tat transgenic female and male mice. Chronic ZCZ011 treatment (10 mg/kg) did not alter body mass, locomotor activity, or anxiety-like behavior regardless of sex or genotype. However, differential effects were noted in hot plate latency, motor coordination, and recognition memory in female mice only, with ZCZ011 treatment increasing hot plate latency and improving motor coordination and recognition memory. Only minor effects or no alterations were seen in the endocannabinoid system and related lipids except in the cerebellum, where the effect of ZCZ011 was more pronounced in female mice. Moreover, AEA and PEA levels in the cerebellum were positively correlated with improved motor coordination in female mice. In summary, these findings indicate that chronic ZCZ011 treatment has differential effects on antinociception, motor coordination, and memory, based on sex and HIV-1 Tat expression, making CB1R PAMs potential treatment options for HAND without the psychoactive side effects.

neuroscience↗

bioRxiv2024

Deep Imputation for Skeleton Data (DISK) for Behavioral Science

AbstractPose estimation methods and motion capture systems have opened doors to quan- titative measurements of animal kinematics. However, these methods are not perfect and contain missing data. Our method, Deep Imputation for Skeleton data (DISK), leverages deep learning algorithms to learn dependencies between keypoints and their dynamics to impute missing tracking data. We developed an unsupervised training scheme, which does not rely on manual annotations, and tested several neural network architectures for the imputation task. We found that transformer outperforms other architectures including graph con- volutional networks that were developed specifically for skeleton-based action recognition. We demonstrate the usability and performance of our imputation method on seven different animal skeletons including two multi-animal set-ups. With an optional estimated imputation error, DISK enables behavior scien- tists to assess the reliability of the imputed data. The imputed recordings allow to detect more episodes of motion, such as steps, and to obtain more sta- tistically robust results when comparing these episodes between experimental conditions. While animal behavior experiments are expensive and complex, track- ing errors make sometimes large portions of the experimental data unusable. DISK allows for filling in the missing information and for taking full advantage of the rich behavioral data. This stand-alone imputation package, freely available at https://github.com/bozeklab/DISK.git, is applicable to results of any track- ing method (marker-based or markerless) and allows for any type of downstream analysis.

animal behavior and cognition↗

bioRxiv2023

Endocannabinoid system modulation alters fine motor behavior in mice: insights from 3D motion capture

The neuromodulatory endocannabinoid system is a promising target for therapeutic interventions. One of the well-known behavioral effects of cannabinoid CB1 receptor activation with exogenous ligands such as THC is the inhibition of locomotor activity. However, the behavioral effects of endogenous cannabinoids are not understood. Enhancing endocannabinoid signaling offers an advantageous therapeutic strategy with limited cannabimimetic side effects, but their effects on motor function remain unclear. To reveal even the finest changes in motor function during voluntary locomotor tasks in mice, we adapted a high-speed, high-resolution marker-based motion capture, which so far has not been available in freely moving mice. Here we show that inhibition of distinct endocannabinoid metabolic pathways produces opposite effects on locomotor behavior that differ from those induced by exogenous cannabinoid receptor ligands. Selective upregulation of endocannabinoids 2-arachidonoylglycerol (2-AG) or N-arachidonoylethanolamine (AEA, anandamide) with inhibitors of their degradation (MJN110 and PF3845, respectively), produced bidirectional effects: MJN110 enhanced and PF3845 suppressed locomotor activity. Consistent differences in whole-body movement and precise step kinematics were found under distinct treatments, while analysis of locomotory episodes revealed invariant temporal microstructure, pointing towards motivational rather than motor-related mechanisms of action. The results show that the effects of manipulations of endocannabinoid system on locomotion are more diverse than previously assumed and result in distinct kinematic phenotypes.

animal behavior and cognition↗

bioRxiv2021

Intravenous haloperidol and cocaine alter the distribution of T CD4+ and B lymphocytes and NKT cells in rats

Modulation of dopamine transmission evokes strong behavioral effects that can be achieved by psychoactive drugs such as haloperidol or cocaine. Cocaine non-specifically increases dopamine transmission by blocking dopamine active transporter (DAT) and evokes behavioral arousal, while haloperidol is a non-specific dopamine D2 receptor antagonist with sedative effects. Interestingly, dopamine has been found to affect immune cells in addition to its action in the central nervous system. Here we address the possible interactions between haloperidol and cocaine and their effects on both immune cells and behavior in freely moving rats. We use an intravenous model of haloperidol and binge cocaine administration to evaluate the drugs impact on the distribution of lymphocyte subsets in both the peripheral blood and the spleen. We assess the drugs behavioral effects by measuring locomotor activity. Cocaine evoked a pronounced locomotor response and stereotypic behaviors, both of which were completely blocked after pretreatment with haloperidol. The results suggest that blood lymphopenia which was induced by haloperidol and cocaine (except for NKT cells), is independent of dopaminergic activity and most likely results from the massive secretion of corticosterone. Haloperidol pretreatment prevented the cocaine-induced decrease in NKT cell numbers. On the other hand, the increased systemic dopaminergic activity after cocaine administration is a significant factor in retaining T CD4+ and B lymphocytes in the spleen. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=90 SRC="FIGDIR/small/470229v2_ufig1.gif" ALT="Figure 1"> View larger version (37K): org.highwire.dtl.DTLVardef@1275eb3org.highwire.dtl.DTLVardef@1ba7afcorg.highwire.dtl.DTLVardef@1e070b9org.highwire.dtl.DTLVardef@886bf_HPS_FORMAT_FIGEXP M_FIG C_FIG

pharmacology and toxicology↗

bioRxiv2017

Salient Experiences are Represented by Unique Transcriptional Signatures in the Brain

Inducible transcription is essential for consolidation of salient experiences into long-term memory. However, the question of whether inducible transcription relays information representing the identity of the experience being encoded, has not been explored. To this end, we have analyzed transcription across multiple brain regions, induced by a variety of rewarding and aversive experiences. Our results define robust transcriptional signatures uniquely characterizing individual salient experiences. A subset of these induced transcriptional markers suffice for near-perfect decoding of the identity of recent experiences at the level of individual mice. Furthermore, experiences with shared attributes display commonalities in their transcriptional representation, exemplified in the representation of valence, habituation and reinforcement. Taken together, our results demonstrate the existence of a neural transcriptional code that represents the encoding of experiences in the mouse brain. This code is comprised of distinct transcriptional signatures that correlate to the affective attributes of the experiences that are being encoded.

neuroscience↗