bioRxiv Subject Collection: Neuroscience's Journal
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Monday, May 19th, 2025
| Time |
Event |
| 4:38a |
Ambient Light Impacts Innate Behaviors of New-World and Old-World Mice
Animals encounter predators and prey under diverse lighting conditions that signal different risks and opportunities, yet how ambient illumination shapes innate approach and avoidance behaviors remains poorly understood. Here we have systematically tested the visually guided behaviors of New-World (North American Peromyscus) and Old-World (Eurasian Mus) mice under conditions mimicking bright daylight or dim moonlit environments. We identified common and species-specific adaptations to the different lighting conditions. Across species, dim light enhanced the speed and vigor of escape responses to predator-like looming stimuli. However, species diverged in their reactions to non-threatening stimuli, with Mus musculus and Peromyscus polionotus increasing aversive behaviors under dim light, while Peromyscus maniculatus showed stronger avoidance under bright conditions. Finally, although ambient light levels had a common effect on exploratory behavior, these changes were not predictive of subsequent visually evoked behaviors. Our findings reveal that ambient lighting profoundly and differentially shapes innate behavioral strategies across species, and demonstrate that these context-specific survival responses are inherited rather than learned. | | 6:03a |
The polyamine naphthyl-acetyl spermine trihydrochloride (NASPM) lacks specificity for Ca2+-permeable AMPA receptors and suppresses seizure like activity in human brain tissue by inhibition of NMDA receptors.
For decades, naphthyl-acetyl spermine trihydrochloride (NASPM) has been used as a selective inhibitor of calcium-permeable AMPA receptors (CP-AMPAR). In rodents, NASPM is known to suppress seizures in vivo and seizure-like events (SLE) in vitro, suggesting possible involvement of CP-AMPAR in ictogenesis and epileptogenesis. To address whether these findings can be translated to human brain, we investigated the involvement of glutamatergic receptor subclasses in SLE in human cortex ex vivo, demonstrating that glutamatergic receptor antagonists can block (NASPM and APV) or reduce (UBP302, GYKI52466, GYKI53655) SLE. Using a multimethodological approach we were able to demonstrate that both NASPM and APV inhibit human SLE by inhibition of NMDA receptors. Our results further show that the inhibitory effect of NASPM on NMDA receptors is sufficient to explain its inhibition of seizure like activity, rather than its action on CP-AMPA receptors. Thus, our findings challenge previous knowledge on the use of NASPM as a specific CP-AMPAR inhibitor. Some phenomena previously attributed to CP-AMPAR, may need to be re-examined more closely. Overall, our study raises awareness about potential pitfalls in the use of existing pharmacological agents and sets a new paradigm for the use of NASPM in neuroscience research while questioning its therapeutic potential in a clinical context. | | 6:30a |
Dynamic regulation of neuronal Vault trafficking and RNA cargo by the noncoding RNA, Vaultrc5
Vaults are large ribonucleoprotein complexes of unknown function in neurons. Here, we report that the Vault-associated noncoding RNA, Vaultrc5, is highly enriched at the synapse and is required for activity-dependent Vault trafficking in neurons. We have discovered that Vaults are comprised of unique populations of coding and non-coding RNA, and that this cargo varies dynamically between subcellular compartments. In addition, Vaultrc5 knockdown at the synapse shifts the RNA cargo toward transcripts associated with immune surveillance, and Vaultrc5 knockdown, in vivo, leads to impaired fear learning. These findings suggest that the Vaultrc5 is critically involved in coordinating the experience-dependent trafficking of Vaults and related RNA cargo, which represents a novel feature of neuronal plasticity underlying learning and memory. | | 6:30a |
High-resolution laminar recordings reveal structure-function relationships in monkey V1
The relationship between the structural properties of diverse neuronal populations in the monkey primary visual cortex (V1) and their functional visual processing in vivo remains a critical knowledge gap in visual neuroscience. We took advantage of high-density Neuropixels electrodes to record large populations of neurons across layers of macaque V1 and used a state-of-the-art non-linear dimensionality reduction approach on waveform shape to delineate nine putative cell classes, 4 narrow-spiking (NS), 4 broad-spiking (BS) and 1 tri-phasic (TP). Then, we performed targeted analyses of laminar organization, spike amplitude, multichannel spatial features, functional properties, and network connectivity of these cell classes, to discover four fundamental aspects of the V1 microcircuit predicted by anatomical studies, but never fully demonstrated before in vivo: First, NS neurons were most concentrated in layer 4 and more numerous than parvalbumin positive neurons, consistent with studies of potassium channel expression in excitatory neurons in V1. Second, a large amplitude NS cell class in layer 4B was strongly direction selective, with multichannel waveforms consistent with a stellate morphology, which is a likely functional correlate of anatomical descriptions of neurons that project between V1 and MT. Third, an NS cell class in layer 4B showed robust bursting activity and strong orientation selectivity. Finally, cross-correlation analysis of neuron pairs revealed distinct functional interactions between cell classes. These results demonstrate that high-resolution electrophysiology enables discovery of novel relationships between structural organization and in vivo functional responses of neurons, and can inform biologically realistic microcircuit models of primate V1, perhaps even extending to all of neocortex. | | 7:47a |
Characterizing the frequency-specific and spatiotemporal dynamics of β-γ Phase-Amplitude Coupling in Parkinson's disease
Cross-frequency coupling (CFC) has been proposed to facilitate neural information transfer across spatial and temporal scales. Phase-amplitude coupling (PAC), a type of CFC in which the amplitude of a faster brain oscillation is coupled to the phase of a slower brain oscillation, is implicated in various higher-order cognitive functions and was shown to be pathologically altered in neurological and psychiatric disease. In Parkinson's disease (PD), the coupling between gamma amplitude (50-150 Hz) to beta phase (13-35 Hz) is exaggerated. Enhanced {beta}-{gamma} PAC was found in the subthalamic nucleus and various cortical sources and shown to be responsive to dopaminergic therapy and deep brain stimulation (DBS). Therefore, exaggerated {beta}-{gamma} PAC has been proposed to be a disease marker and a potential target for brain circuit interventions. Despite these promising findings, a significant knowledge gap remains, as the spatial and frequency-specific dynamics of {beta}-{gamma} PAC and its association with motor symptoms and therapy remain elusive. To address this knowledge gap, we employed high-density electroencephalography (EEG) with advanced source localisation techniques for PD patients at rest. We highlight three key findings: (1) a frequency-specific increase in high {beta} (23-35 Hz)-{gamma} PAC within and between sources of the cortical motor network, (2) a link between elevated high {beta}-{gamma} PAC and bradykinesia and rigidity when OFF medication, but not tremor, and (3) a medication-induced reduction in high {beta}-{gamma} PAC in the supplementary motor area correlating with clinical improvement. Altogether, this study provides novel insights into the pathophysiology of PD as an oscillopathy and identifies high {beta}-{gamma} PAC as a potential marker of Parkinsonian symptoms and treatment effects. This has important implications for invasive as well as non-invasive therapeutic strategies as high {beta}-{gamma} PAC targeting might hold greater promise than targeting {beta}-{gamma} PAC per se. | | 2:20p |
Proprioceptive limit detectors mediate sensorimotor control of the Drosophila leg
Many animals possess mechanosensory neurons that fire when a limb nears the limit of its physical range, but the function of these proprioceptive limit detectors remains poorly understood. Here, we investigate a class of proprioceptors on the Drosophila leg called hair plates. Using calcium imaging in behaving flies, we find that a hair plate on the fly coxa (CxHP8) detects the limits of anterior leg movement. Reconstructing CxHP8 axons in the connectome, we found that they are wired to excite posterior leg movement and inhibit anterior leg movement. Consistent with this connectivity, optogenetic activation of CxHP8 neurons elicited posterior postural reflexes, while silencing altered the swing-to-stance transition during walking. Finally, we use comprehensive reconstruction of peripheral morphology and downstream connectivity to predict the function of other hair plates distributed across the fly leg. Our results suggest that each hair plate is specialized to control specific sensorimotor reflexes that are matched to the joint limit it detects. They also illustrate the feasibility of predicting sensorimotor reflexes from a connectome with identified proprioceptive inputs and motor outputs. | | 4:15p |
Personalized whole-brain models of seizure propagation
Computational modeling has recently emerged as a powerful tool to better understand seizure dynamics and guide new treatment strategies. This work presents a method for personalizing whole-brain computational models in epilepsy, integrating SEEG, MRI, and diffusion MRI data to enhance therapeutic approaches. The objective of this method is to construct a mechanistic model replicating seizure propagation from the epileptogenic network to the entire brain, which can then be used to simulate and evaluate patient-specific therapeutic interventions. The pipeline uses neural mass models for each node in the network, simulating whole-brain dynamics. Model personalization involves adjusting global and local parameters representing the excitability of individual brain areas, using an evolutionary algorithm that aims to maximize the correlation between empirical and synthetic functional connectivity matrices derived from SEEG data. The resulting personalized models successfully reproduce individual seizure propagation patterns and can be used to simulate therapeutic interventions like surgery, stimulation, or pharmacological interventions within a unified physiological framework. Notably, model predictions reveal distinct patient-specific responses across interventions, highlighting the potential of whole-brain modeling to guide individualized treatment by identifying accessible and functionally relevant targets. |
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