bioRxiv Subject Collection: Neuroscience's Journal
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Thursday, March 13th, 2025
| Time |
Event |
| 11:31a |
Single-cell resolution spatial transcriptomic signature of the retrosplenial cortex during memory consolidation
The retrosplenial cortex (RSC) is a critical brain region activated during spatial memory tasks and plays an underlying role in long-term memory consolidation. The RSC comprises multiple cell types, including different classes of excitatory neurons across laminar layers. These layer-specific cells form the hub of neuronal connection between the RSC and other brain regions, including the hippocampus. Despite the established role of the RSC in spatial memory, the transcriptomic signature of the neuronal sub-types in the RSC during spatial memory consolidation remained elusive. Here we used both unbiased and targeted spatial transcriptomic approaches to illuminate the transcriptional signature of the RSC following a spatial memory task. We found that genes related to transcription regulation, protein folding, and mitogen-activated protein kinase pathways were upregulated in the RSC after spatial learning during an early time window of memory consolidation. Further, cell type and excitatory neuronal layer-specific changes in gene expression were resolved using Xenium spatial transcriptomics. The distinct signatures of memory-responsive genes were observed in excitatory neurons across the laminar layers of the RSC following learning. Finally, we observed that blocking RSC excitatory neurons during the early temporal window after learning using a chemogenetic approach impaired long-term spatial memory. Overall, our results uncover a molecular signature of the RSC after learning and demonstrate the role of RSC excitatory neurons during the early time points of memory consolidation. This study underscores the importance of the learning-induced transcriptional signature of the RSC in long-term spatial memory consolidation and reveals a cell-type specific signature of memory-responsive gene expression. | | 11:31a |
APP overexpression delays synaptic development and alters neuronal network properties
The amyloid precursor protein (APP) regulates neuronal excitability by altering the structure of the axon initial segment. Using high density multielectrode arrays we compared the electrophysiological consequences of APP overexpression with exposure to {beta}-amyloid (A{beta}) and found that the two manipulations affected neural activity in largely non-overlapping ways. In mature cultures (>18 days in vitro, DIV18), APP reduced the firing probability of individual neurons, while {beta}-amyloid stripped synapses impacting whole-network connectivity. In immature cultures (DIV10), increasing APP- either acutely with lentiviral vectors or genetically by culturing APP transgenic neurons - revealed a separate developmental function. Synaptogenesis and axonal branch formation were blocked. A{beta}, by contrast, interfered primarily with network behavior. Our findings suggest that Alzheimer's disease is likely an amalgamation of APP mis-regulation plus the effects of A{beta} accumulation. They also urge consideration of the idea that familial and sporadic forms of Alzheimer's may represent distinct disease processes. | | 11:31a |
Prefrontal default-mode network interactions with posterior hippocampus during exploration
Hippocampal maps and ventral prefrontal cortex (vPFC) value and goal representations support foraging in continuous spaces. How might hippocampal-vPFC interactions control the balance between behavioral exploration and exploitation? Using fMRI and reinforcement learning modeling, we investigated vPFC and hippocampal responses as humans explored and exploited a continuous one-dimensional space, with out-of-session and out-of-sample replication. The spatial distribution of rewards, or value landscape, modulated activity in the hippocampus and default network vPFC subregions, but not in ventrolateral prefrontal control subregions or medial orbitofrontal limbic subregions. While prefrontal default network and hippocampus displayed higher activity in less complex, easy-to-exploit value landscapes, vPFC-hippocampal connectivity increased in uncertain landscapes requiring exploration. Further, synchronization between prefrontal default network and posterior hippocampus scaled with behavioral exploration. Considered alongside electrophysiological studies, our findings suggest that locations to be explored are identified through coordinated activity binding prefrontal default network value representations to posterior hippocampal maps. | | 11:31a |
Dense Longitudinal Precision Neuroimaging of Recovery from Traumatic Brain Injury
Traumatic brain injury (TBI) disrupts white matter tracts essential for cognition and emotion. Diffusion tensor imaging (DTI) can noninvasively measure white matter integrity. However, DTI has been inconsistent in predicting patient recovery from TBI, possibly due to the complex, dynamic, and individual-specific process of post-TBI white matter remodeling. Here, we employed dense longitudinal neuroimaging to track white matter recovery weekly over six months after a TBI within a single patient and a control in a similar age group (21 vs. 24 y.o.). In the patient, but not in the control, DTI metrics precisely tracked parabolic trajectories across time, with early structural alterations continuing for more than 15 weeks before reversing direction. The extent of alteration in each tract was correlated with the time until reversal. These continuous DTI changes also mediated recovery of cognitive and emotional function, suggesting they are not passive markers of damage but dynamic processes underlying functional improvement. Complementary diffusion basis spectrum imaging (DBSI) revealed an initial phase of cellular loss followed by inflammatory remodeling, vascular adaptations, and persistent metabolic activity. Our findings indicate that recovery does not follow predefined phases but rather individualized transition points, which could define optimal windows for rehabilitation. Identifying these inflection points may enable personalized interventions aligned with biologically relevant structural shifts, rather than broad recovery periods. | | 11:31a |
Burnout in nurses and biomarkers of stress, inflammation and neuroplasticity.
Burnout is an occupational challenge to the health, performance, and retention of healthcare personnel. The objective of this cross-sectional study was to further our understanding of the association between burnout, work, coping, and cognitive impairment as it relates to neuroendocrine, inflammatory, and neuroplastic disease mechanisms. One hundred hospital-based registered nurses responded to a validated survey addressing employment and work characteristics, coping, and cognitive impairment, and a one-item, burnout scale. In addition, they all provided blood samples. Nineteen percent of the nurses reported symptoms of evolving burnout and an additional 12% reported established burnout. Severity of burnout was inversely associated with self-rated energy (p<.001), ability to concentrate (p<.001), and positively associated with stressed at work (p<.001), but not with workplace cognitive impairment. The anti-inflammatory and pro-energetic biomarker interleukin-10 was elevated in respondents in the combined two highest burnout categories (mean 2.81, S.E.M. 0.26 pg/mL) vs. a median of 2.09 pg/mL in the no-burnout category (p<.02). When biomarkers in blood were regressed on severity of burnout, concentration of the anabolic hormone dehydroepiandro{-}sterone{-}{-}-sulfate (standardized beta -.73, p=.007) and the neuronal strain biomarker neurofilament light chain (-.79, p=.01) inversely predicted burnout. In contrast, the ability to cope with a tough situation at work was positively associated with burnout (.75, p=.02). The study not only confirms the association between burnout and self-reported individual and work-related adverse outcomes but, importantly, burnout-relevant neuroendocrine, inflammatory, and neuronal biomarkers. Nurses suffering from burnout might exhibit dysfunctional coping resulting in decreased recognition of low energy, which accelerates the burnout process. It is proposed that assessment of biological disease mechanisms should play a larger role in both scholarly and clinical burnout work. | | 11:31a |
Cortical reinstatement of causally related events sparks narrative insights by updating neural representation patterns
We make sense of everyday events by reasoning about their underlying causes. When we connect causal links between events separated in time, we often experience a sudden feeling of "aha!", or a moment of insight. What cognitive and neural processes underlie these moments of understanding? We hypothesized that narrative insight accompanies retrieving causally related past events in memory and updating the current event representation. To test this, we designed an fMRI study in which participants watched a TV episode that was cut into multiple events and presented in temporally scrambled orders. Participants pressed an "aha" button whenever they understood something new and verbally explained why they pressed in those moments at the end of each run. Supporting our prediction, more than 40% of insights included the retrieval of past events that were causally related to the current event. Neural patterns representing causally related past events were reinstated in cortical areas. This neural reinstatement drove sudden shifts in cortical representation patterns ~2 s prior to aha button presses, reflecting an update in situational representation at moments of insight. Moreover, distributed areas in the brain represented causally related events with similar neural patterns, beyond their shared semantic or perceptual features. Together, the study suggests that we comprehend events by reinstating causally related past events via shared neural patterns, followed by updating neural patterns at moments of insight. | | 11:31a |
Human-specific morphoregulatory signatures in basal radial glia characterize neocortex evolution
As the seat of our cognition, the human neocortex is an object of immense fascination. Human neocortex expansion during evolution has been attributed to an increase in the proliferative capacity of neural progenitor cells during development, particularly basal radial glia (bRG). Despite their evolutionary relevance, the genomic changes driving human-specific bRG biology remain uncharacterized. We used comparative chromatin and transcriptional profiling of neural progenitor cells isolated from gorilla, chimpanzee and human cerebral organoids to identify cis-regulatory elements that have gained activity in humans. Focusing specifically on bRG, we discovered that morphoregulatory enhancer activity and gene expression signatures distinguish human bRG from other great apes. Functional analysis of the morphoregulatory genes FAM107A and CNGA3 in human organoids revealed that these genes are required for the morphological complexity of human bRG. Taken together, our interspecies comparison of basal radial glia suggests that human-specific morphoregulatory signatures characterize neocortex evolution. | | 2:18p |
Mapping the magnetoreceptive brain: A 3D digital atlas of the migratory bird Eurasian blackcap (Sylvia atricapilla)
Birds undisputedly range amongst natures foremost navigators. To successfully navigate between breeding and wintering quarters, they, in addition to other natural orientation cues, rely on their ability to sense the Earths magnetic field. For this reason, migratory birds have become key model species for studying the sensory mechanisms underlying magnetic field-guided navigation, as evidenced by the identification of several brain regions believed to be involved in processing magnetic field information. However, there is as yet no readily accessible, high-resolution three-dimensional (3D) brain atlas to serve as a common reference within and across studies. Here we provide the neuroscience research community with the first freely available, digital, high-resolution (25 {micro}m), 3D bird brain atlas. It is based on light microscopy images from ten Eurasian blackcaps (Sylvia atricapilla), a night-migratory songbird widely used model species in magnetoreception and navigation research. We outline the individual steps for the creation of a brain atlas, from whole-brain imaging using serial-section, two-photon tomography, to the creation of an average template at an isotropic 25-{micro}m voxel size, and finally to brain area segmentation and annotation. In this first version of the atlas, we have mapped a total of 24 brain areas, including 6 principal compartments, 13 conspicuous anatomical subdivisions common to all bird species and 5 functionally defined areas of the visual and trigeminal sensory systems involved in processing magnetic field information. This atlas is accessible via the standardised BrainGlobe Atlas API, making it compatible with a growing suite of computational neuroanatomy tools provided by the BrainGlobe Initiative. This integration enables precise alignment of future experimental data to a common coordinate space, facilitating collaboration, data visualization and sharing. Furthermore, this resource enables the accurate localization and comparison of implanted devices, injection sites, and/or cell populations across individual brains, both within and across studies. | | 3:32p |
Neuroanatomical foundations of social tolerance across macaque species
The macaque genus includes 25 species with hugely diverse social systems, ranging from low to high tolerance social organization. Such interspecific behavioral variability provides a unique model to tackle the evolutionary foundation of primate social brain. Yet, the neuroanatomical correlates of these social tolerance grades remain unknown. To address this question, we analyzed post-mortem structural scans from 12 macaque species. Our results show that amygdala volume is a subcortical predictor of macaques social tolerance, with high tolerance species exhibiting larger amygdala than low tolerance ones. To tackle the issue of nature versus nurture origin of the social tolerance effect on amygdala volume, we investigated the development of amygdala across species with different social grades. Intolerant species showed a gradual increase in relative amygdala volume across the lifespan. Unexpectedly, tolerant species exhibited an opposite trend, previously undescribed in primates. Taken together, these findings provide valuable insights into the neuroanatomical and evolutionary basis of primates social behaviors. | | 8:34p |
Reactivating a relaxation exercise during sleep to influence cortical hyperarousal in people with frequent nightmares - a randomized crossover trial
Study Objectives High-frequency EEG activity during sleep (cortical hyperarousal), is a transdiagnostic feature across psychiatric disorders, including nightmare disorder. It is discussed as a target of intervention; however, specific treatment options are yet unavailable. We tested whether exposure to relaxation-associated odor cues during sleep would reduce cortical hyperarousal, i.e. beta (16.25 - 31 Hz), gamma (31.25 - 45 Hz), spindle activity and nightmare occurrence in participants with frequent nightmares. Methods Twenty-five (21 female, mean age (SD) = 24.94(5.01)) participants, recruited from undergraduate students at University of Luebeck, with [≥]1 nightmare / week received a deep breathing relaxation intervention for one week coupled with an odor. On two subsequent nights in the sleep laboratory, the associated odor (A), or control odor (B) were presented in randomized order in a crossover design with randomization at baseline; participants were blinded to intervention. Results N = 11 participants were allocated to AB and n = 14 to BA sequence. Exposure to relaxation-associated odor cues during sleep did not affect beta or gamma activity while spindle count and density were significantly reduced. Reduction in spindle count during reactivation nights correlated with reduced subjective wake-after-sleep-onset. There was no additional impact on nightmare symptoms. There were no adverse events or side effects. Conclusions The reactivation of relaxation-associated states with odor cues during sleep may be associated with changes in spectral activity, specifically spindle activity. Future studies should implement multiple nights of reactivation and include different patient groups with cortical hyperarousal to test the transdiagnostic potential of this new intervention. |
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