Search arXiv⌕ Search
Home/Archive/arXiv

arXiv · 2402.05815

Effects of kappa-opioid agonist U-50488 and p38 MAPK inhibitor SB203580 on the spike activity of pyramidal neurons in the basolateral amygdala

Konstantin Y. Kalitin·Alexander A. Spasov·Olga Y. Mukha
View original source ↗Read source document ↗Export metadata ↓

Abstract

Introduction: Kappa-opioid receptor (KOR) signaling in the basolateral amygdala (BLA) underlies KOR agonist-induced aversion. In this study, we aimed to understand the individual and combined effects of KOR agonist U-50488 and p38 MAPK inhibitor SB203580 on the spiking activity of pyramidal neurons in the BLA to shed light on the complex interplay between KORs, the p38 MAPK, and neuronal excitability. Materials and Methods: Electrophysiological experiments were performed using the patch-clamp technique in the whole-cell configuration. Rat brain slices containing the amygdala were prepared, and pyramidal neurons within the BLA were visually patched and recorded in the current clamp mode. The neurons were identified by their accommodation properties and neural activity signals were amplified and analyzed. Using local perfusion, we obtained three dose-response curves for: a) U-50488 (0.001-10 μM); b) U-50488 (0.001-10 μM) in the presence of SB203580 (1 μM); and c) U-50488 (0.01-10 μM) in the presence of SB203580 (5 μM). Results: After the application of U-50488, pyramidal neurons had a higher action potential firing rate in response to a current injection than control neurons (p<0.001). The dose-dependent curves we obtained indicate that the combination of U-50488 and SB203580 results in non-competitive antagonism. This conclusion is supported by the observed change in the curve`s slope with reduction in the maximum effect of U-50488. Thus, it can be assumed that the increase in spike activity of pyramidal neurons of the amygdala is mediated through the beta-arrestin pathway. When this pathway is blocked, the spike activity reverts to its baseline level. Conclusion: Our study found that the KOR agonist-induced spiking activity of the BLA pyramidal neurons is mediated by the beta-arrestin pathway and can be suppressed by the application of the p38 MAPK inhibitor SB203580.

Explore related subjects

q-bio.NC

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Konstantin Y. Kalitin, Alexander A. Spasov, Olga Y. Mukha. 2024-02-17. Effects of kappa-opioid agonist U-50488 and p38 MAPK inhibitor SB203580 on the spike activity of pyramidal neurons in the basolateral amygdala. https://doi.org/10.18413/rrpharmacology.10.400

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related papers

arXiv2026

Only what exists can cause: An intrinsic powers view of free will

This essay addresses the implications of integrated information theory (IIT) for free will. IIT is a theory of what consciousness is and of how its presence and quality can be accounted for in physical terms. According to IIT, the presence of consciousness is accounted for by a maximum of cause-effect power in the brain. Moreover, the way an experience feels is accounted for by how that cause-effect power is structured. If IIT is right, we do have free will in a genuine sense: we have alternatives, reasons, and values, we make decisions, and we-not our neurons or atoms-are the cause of our willed actions and bear responsibility for them. IIT's argument for genuine free will hinges on the proper understanding of consciousness as intrinsic existence, captured by its intrinsic powers ontology: what exists absolutely, in physical terms, are intrinsic entities, and only what exists can cause.

q-bio.NC↗
arXiv2026

Seeing the imagined: latent functional alignment in visual imagery decoding from fMRI data

Recent progress in visual brain decoding from fMRI has been enabled by large-scale datasets such as the Natural Scenes Dataset (NSD) and powerful diffusion-based generative models. While current pipelines are primarily optimized for perception, their performance under mental-imagery remains less well understood. In this work, we study how a state-of-the-art (SOTA) perception decoder (DynaDiff) can be adapted to reconstruct imagined content from the NSD-Imagery benchmark. We propose a latent functional alignment (LFA) approach that maps imagery-evoked activity to the pretrained model's semantic content-enriched conditioning space, by adding a simple alignment module, while keeping the original remaining components frozen. To mitigate the limited amount of matched imagery-perception supervision, we further introduce a neural retrieval-based augmentation strategy that selects semantically related NSD perception trials from the same participants. Across four subjects, LFA consistently improves high-level semantic reconstruction metrics relative to the frozen pretrained baseline and a voxel-space ridge alignment baseline, and enables above-chance decoding from multiple cortical regions. These results suggest that semantic structure learned from perception can be leveraged to stabilize and improve visual imagery decoding under out-of-distribution conditions.

q-bio.NC↗
arXiv2026

Deep Learning in Infant Functional Neuroimaging: Challenges, Advances, and Future Directions

Infancy is a critical developmental window characterized by rapid functional brain reorganization, during which large-scale networks emerge, individualized connectome signatures continue to form, and early deviations may shape long-term cognitive and clinical outcomes. Functional MRI (fMRI) offers an opportunity to study these processes in vivo, yet extracting developmentally meaningful information from it remains challenging due to comparatively short scan duration, structured motion artifacts, variable scan states, and rapid brain maturation. Amid these challenges, deep learning has expanded the capacity of computational neuroimaging by learning robust representations from noisy, high-dimensional data, integrating complex spatial and temporal information, and capturing the nonlinear and rapidly evolving organization of the developing brain. Here, we review recent advances in deep learning for infant functional neuroimaging, synthesizing progress across input representation formatting, population and individualized brain mapping, longitudinal trajectory forecasting, robust and explainable model evaluation, and biological translation. Collectively, these methodological advances mark a paradigm shift in infant functional neuroimaging from descriptive, group-level analyses toward reliable, individualized, and developmentally grounded models. Future progress will depend on larger and more diverse longitudinal datasets, developmentally appropriate model designs, rigorous and standardized evaluation, and integration of computational predictions with biological mechanisms towards clinically meaningful outcomes. Addressing these priorities will help establish deep learning as a robust framework for understanding early functional brain development, identifying developmental variation at the individual level, and ultimately supporting earlier and precise assessment of neurodevelopmental risk.

q-bio.NC↗