Osmanski, B. F. | bioRxiv Science

bioRxiv2026

Temporal Patterns of Brain Network Plasticity During the Onset and Maintenance of Neuropathic Pain in Male Mice

Neuropathic pain arises from complex peripheral and central mechanisms and induces long-lasting maladaptive changes in the brain. To investigate the temporal dynamics of these changes, we examined resting-state functional connectivity (FC) in a mouse model of neuropathic pain across its initiation and maintenance phases. Using functional ultrasound imaging to capture whole-brain FC over disease progression, we conducted two complementary studies: a longitudinal assessment in anesthetized animals and an analysis of awake cohorts at distinct disease stages. Both exploratory and literature-guided analyses revealed that FC across most large-scale networks remained remarkably stable during pain maintenance. In contrast, pain onset was marked by enhanced FC between key regions involved in sensory, emotional, and motivational processing, including the motor cortex and nucleus accumbens, the prelimbic and insular cortices, and the infralimbic cortex and hypothalamus. As pain persisted, we observed reduced FC within the somatomotor network, reflecting functional disconnection. Additionally, postsurgical pain alone produced enduring FC changes within the prefrontal cortex, hippocampus, and insula, indicating long-term central plasticity independent of neuropathic injury. Together, these findings reveal dynamic, network-specific adaptations that distinguish the onset and maintenance phases of neuropathic pain and surgery-related plasticity.

neuroscience↗

bioRxiv2025

Speed Vascular Patterns in the Spatial Navigation System

The hippocampal formation is central to spatial navigation, hosting neurons that encode position, direction, and speed. Yet, the brain-wide vascular dynamics supporting these processes remain poorly understood, especially during naturalistic behaviors. Here, we adapted functional ultrasound (fUS) imaging to examine how cerebral blood volume (CBV) changes relate to behavioral parameters in freely moving rats. High-resolution imaging of hippocampal-parahippocampal regions during open-field exploration reveals strong correlations between CBV dynamics and animal speed, with distinct regional activation patterns and temporal delays. Lagged general linear modeling uncovers information flow from the thalamus to parahippocampal regions, including the medial entorhinal cortex, and to hippocampal subfields (dentate gyrus, CA1-CA3), consistent with a hierarchical processing framework. The analysis also links CBV with angular head speed and the dorsal thalamus. Decoding analyses show that CBV signals not only encode speed precisely but also capture spatial features like proximity to walls and corners, even when univariate analyses do not. This decoding remains robust across animals, underscoring the universality of speed encoding in vascular dynamics. We also identify slow CBV oscillations in the hippocampus aligned with minute-scale speed fluctuations, suggesting a neurovascular signature of exploratory behavior. These findings reveal a hemodynamic signature of speed representation in the navigation system, arising from energy demands in a continuous attractor network model for path integration, where population activity and synaptic currents increase quadratically with animal speed as both peak firing rates and neuronal recruitment scale linearly with animal speed. Moreover, they highlight functional ultrasound imaging as a powerful approach for probing the hemodynamic basis of navigation.

neuroscience↗