Organelle trafficking is essential for neuronal function and homeostasis, particularly in dendrites where transport is required to maintain complex arbors. Following dendritic injury, extensive cellular reorganization occurs during regeneration, yet how this remodeling affects organelle transport dynamics remains poorly understood. To assess the consequences of regeneration on dendritic trafficking, we examined Rab7-labeled late endosome (LE) movement in class IV dendritic arborization neurons of Drosophila after dendrite injury. Using quantitative live imaging analysis, we found that retrograde LE trafficking speed is significantly reduced in regenerated dendrites compared to uninjured controls. However, anterograde LE trafficking speed, the directional bias of LE movement, the proportion of motile versus stationary organelles, LE number, and run length were not significantly different between uninjured versus regenerated neurons at either time point examined. These findings demonstrate that dendritic regeneration selectively impairs retrograde transport kinetics while preserving anterograde transport and directional control mechanisms. Regenerated dendrites are thinner than uninjured controls at early stages of regrowth but recover to normal caliber by later stages, yet retrograde transport deficits persist, suggesting caliber-independent regulation of retrograde transport speed. Our results suggest that altered organelle trafficking dynamics may represent a fundamental consequence of neuronal injury responses, with potential implications for understanding transport defects in regeneration after injury or disease involving dendritic damage.
Introduction: Environmental heat stress and displacement adversity during pregnancy pose significant risks to neurodevelopment, particularly in regions with high maternal mortality and population displacement. The suprachiasmatic nucleus (SCN), the brain's master circadian pacemaker, is vulnerable to prenatal environmental insults, yet the combined impact of thermal and psychosocial stressors on SCN development remains unexplored. We examined the effects of prenatal heat stress and displacement-like conditions on SCN morphology and behaviour across two critical developmental stages. Methods: Twenty-five timed-pregnant Long-Evans rats were exposed to heat stress (38-40°C, 2h daily), displacement conditions (overnight food/water restriction plus overcrowding), combined stressors, or control conditions from gestational days 15-20. Male offspring were assessed at postnatal days 10 (neonatal) and 30 (juvenile). Results: Heat exposure induced significant maternal hyperthermia (2.5-2.9°C elevation). Histological analysis revealed marked SCN cellular degeneration across stress groups at both developmental stages, characterised by reduced cell counts, pyknotic nuclei, and disrupted tissue architecture. Despite structural damage, juvenile behavioural testing revealed paradoxical outcomes: combined stress exposure reduced anxiety-like behaviour in the elevated plus maze, enhanced sociability in three-chamber testing, while preserving recognition memory. Growth analysis demonstrated preferential brain sparing despite reduced somatic growth, with significantly elevated brain-to-body weight ratios in stress-exposed animals. Conclusion: These findings demonstrate that prenatal environmental stressors cause lasting SCN damage but trigger adaptive behavioural responses. The dissociation between structural vulnerability and functional adaptation suggests complex neurodevelopmental programming with implications for populations experiencing heat exposure and displacement adversity.
INTRODUCTION:Granular neurons arise from external granular precursors (EGPs) in the external granule layer and internal granular progenitors (IGPs) in the internal granule layer (IGL) during cerebellar cortical histogenesis in ferrets. Additionally, IGPs have a potency on differentiating into Bergmann glia and astrocytes. This study aimed to clarify the effects of lipopolysaccharide (LPS) on granular neurogenesis in the developing ferret cerebellum and its association with the proliferation, differentiation, and apoptosis of EGPs and IGPs. METHODS:LPS (500 µg/g body weight) was administered to ferrets at postnatal days (PDs) 6 and 7. Ferrets also received 5-ethynyl-2'-deoxyuridine (EdU) and 5-bromo-2'-deoxyuridine (BrdU) on PDs 5 and 7, respectively, to label post-proliferative and proliferating cells at the time of LPS exposure. RESULTS:Two h after BrdU injection (PD 7), the densities of proliferating BrdU- and post-proliferative EdU-labeled cells did not differ in the external granular layer, molecular/Purkinje cell layers (ML/PCL), or IGL between LPS-exposed and control ferrets. BrdU-labeled cells contained 55-83% cells immunostained for proliferating cell nuclear antigen (PCNA), selectively expressed in IGPs. The S100-immunostained ratio among BrdU-labeled cells was significantly higher in the ML/PCL, but lower in the IGL of LPS-exposed ferrets compared to controls. On PD 20, NeuN-positive granular neurons generated on PD 7 (BrdU-labeled) were significantly denser in the IGL of LPS-exposed ferrets. CONCLUSION:These findings suggest that LPS enhances granular neurogenesis in the developing cerebellum of ferret neonates. LPS may have a location-specific effect on the glial differentiation of proliferating IGPs: enhancing and reducing in the ML/PCL and IGL, respectively.
Introduction: Atypical sensory processing, particularly auditory hypersensitivity, is a common and debilitating phenotype of fragile X syndrome (FXS). Electrophysiology studies in the FMR1-knockout (KO) mice previously observed hyperexcitability at the auditory cortex (AC), with enhanced neuronal firing to auditory stimuli. Prepulse inhibition, a behavioral measure of sensorimotor gating, is robustly impaired in FXS individuals. Interestingly, a related paradigm called gap-induced inhibition of the acoustic startle (GPIAS) is mediated by the AC, and a previous study observed decreased GPIAS in mature FMR1-KO mice. Further, habituation is also an important sensory filtering mechanism, which has been reported to be impaired in mature FMR1-KO mice. However, not much is known about GPIAS and habituation in the FMR1-KO mice during early development. Methods: We evaluated GPIAS in male and female FMR1-KO mice at post-natal days 15 (P15), 20 (P20), and 30 (P30). The paradigm consisted of a prepulse stimulus (gap in continuous background noise) followed by a startle stimulus, at inter-stimulus intervals of 50 and 100 ms. Habituation was assessed prior to the GPIAS trials, with a series of startle only stimulus. Results: We observed a trend for genotype difference in acoustic startle response (ASR) magnitude, particularly in the female mice at P30. No significant genotype differences were noted in GPIAS or latency of ASR. Response duration was significantly increased in the male FMR1-KO mice compared to their WT counterparts during early development. Significant genotype differences were also observed in habituation and sensitization. In terms of development, we observed a significant increase in GPIAS with maturation. Furthermore, we also observed significant changes in the magnitude, response latency, and duration of ASR with maturation. Finally, significant sex differences were observed in ASR magnitude and duration. Conclusion: Our findings suggest that behavioral responses to auditory stimuli are dynamic during development and differ between females and males. This is an important consideration for future study designs and highlights the need for mechanistic studies to further understand the development- and sex-related differences. Additionally, the FMR1-KO mice display habituation deficits during early development, which could be an ideal window for addressing auditory hypersensitivity in FXS.
Cognitive development in late childhood and adolescence occurs alongside increasingly complex environments. To examine how cognitive abilities relate to neural processing of naturalistic experiences, we analyzed fMRI data from 309 children and adolescents (ages 7-15; majority White) in the Healthy Brain Biobank. Participants watched a 10-minute clip of Despicable Me during scanning and completed the WISC. Intersubject correlation (ISC) was used to measure brain synchrony during viewing. Adolescents (11-15) with higher cognitive scores showed greater ISC in default mode and frontoparietal networks. In contrast, younger children (7-11) with high scores showed increased between-subject synchrony only in somatosensory regions. These findings suggest age- and cognition-related differences in how children and adolescents process complex, real-world stimuli.
