bioRxiv Subject Collection: Neuroscience's Journal
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Thursday, August 14th, 2025
| Time |
Event |
| 8:31a |
Guided by Noise: Correlated Variability Channels Task-Relevant Information in Sensory Neurons
Shared trial-to-trial variability across sensory neurons is reliably reduced when perceptual performance improves, yet this variability is low-dimensional, so it could be ignored by an optimal readout mechanism. Why then is it so consistently related to behavior? We propose that shared variability reflects the information communicated to downstream areas, rather than noise to be avoided. Using a circuit model, we show that when sensory signals align with shared variability, behaviorally relevant information is amplified without compromising coding fidelity. Analyses of neural population recordings from multiple brain areas and tasks reveal that the dominant axis of shared variability consistently aligns with task-relevant stimulus features and action plans. Finally, the behavioral impact of microstimulation can be explained by the extent to which it changes projections onto the shared variability axis. These findings suggest that shared variability may illuminate, rather than obscure, the neural dimensions that guide behavior. | | 8:31a |
BIOPHYSICAL MECHANISMS UNDERLYING THE GENERATION AND MAINTENANCE OF RULE-LEARNING ENGRAM
Training rodents in a particularly difficult olfactory-discrimination task results with acquisition of high skill to perform the task superbly, termed rule-learning. We show that rule-learning occurs abruptly, in a "light bulb moment". Using whole-cell patch-clamp recordings in the piriform cortex of Fos2A-iCreER/TRAP2 mice, we targeted activated neurons, expressing immediate early genes (IEG). From the onset of training, IEG-positive neurons from trained animals display enhanced intrinsic excitability. Subsequently, synaptic excitation and inhibition is enhanced in these neurons, in a coordinated, cell-wide process. In parallel, the density of IEG-expressing neurons sharply declines. Double labeling with TRAP and c-Fos reveals that nearly two-thirds of the rule-memory engram neurons were engaged from the beginning of training. Silencing TRAP-expressing neurons using DREADDs leads to a complete loss of rule memory. We propose that rule learning occurs at a discrete moment, and is developed through a gradual process that stabilizes the memory of the rule. | | 8:31a |
Rethinking synthesis and function of neuro-estrogen and neuro-androgen in the hippocampus: some methodological problems and possible solutions
Local synthesis and action of neuro-estrogen and neuro-androgen (including neuro-estradiol (nE2) and neuro-testosterone (nT) have become recognized as key mechanisms in modulation of neural plasticity and cognitive performance, in addition to the contribution of circulating sex steroids. However, still several methodological problems are left to be solved in order to get an better understanding of functions of neural sex steroids in the brain. Here we describe and discuss important improvements in the methods for determination of accurate concentrations of nE2 and nT in rat hippocampus (Section 1), and in methods for analysis of the dendritic spine density in castrated male rat hippocampus (Section 2). The improvements are discussed in order to solve the following two problems. One problem is that the previously reported nE2 concentrations in the hippocampus were widely distributed between ~3 pg/g tissue and ~2 ng/g tissue (i.e., between ~11 pM and ~7 nM) (Section 1). The other problem is that the degree of decrease in hippocampal spine density by castration in male rat hippocamps was strongly dependent on surgical skills of operators (surgeons) (Section 2). | | 8:31a |
Neural Oscillations during Perceptual Grouping: Insights from Alpha and Theta Bands in Visual Perception Tasks
Perceptual grouping, the brain ability to organize visual stimuli into coherent objects and patterns, is thought to rely on distinct neural oscillations across various frequency bands. However, the specific contributions of these frequency bands to perceptual grouping remain a central question in cognitive neuroscience. Our study employs spectral analysis and time- frequency analysis techniques to analyze EEG data collected during visual perception tasks. By examining the temporal dynamics and frequency-specific activity, particularly focusing on the alpha and theta bands immediately following stimulus onset, our goal is to uncover the neural processes underlying perceptual grouping. Our findings indicate significant changes in alpha and theta band activity associated with perceptual grouping in the brain. These results suggest that alpha band oscillations may play a role in directing attention and filtering relevant visual information, while theta band oscillations might facilitate the integration of visual elements into coherent percepts by engaging memory processes and enhancing neural communication across brain regions. This research contributes to a deeper understanding of how neural oscillations coordinate to support perceptual organization, potentially informing future studies and therapeutic approaches aimed at enhancing visual perception and cognitive function. | | 9:45a |
Astrocytic Regulation of aberrant perineuronal net formation in Mecp2-null Neocortex
Rett syndrome (RTT), caused by mutations in MECP2, is a complex neurological disorder characterized by myriad physiological disruptions, including early closure of the critical period of developmental plasticity and precocious formation of perineuronal nets (PNNs). PNNs are lattice-like substructures of extracellular matrix (ECM) that enwrap specific subpopulations of neurons. PNNs are essential in the modulation of neuronal plasticity and brain maturation, and their enzymatic disruption can partially restore plasticity in adults and improve memory. Although precocious PNN formation is well-established in RTT, little is known of the cellular, molecular, or biochemical underpinnings of their precocious formation, or whether precocious PNN formation is due to cell-autonomous or non-cell-autonomous mechanisms. While PNNs form on subsets of neurons throughout the brain, astrocytes secrete many ECM components that form PNNs, and they play a central role in controlling closure of the critical period. We find that Mecp2-null astrocyte conditioned media induces the expression of the key PNN component Hapln1 and causes enhanced PNN formation on wildtype neurons, suggesting that Mecp2-null astrocytes play a key role in the precocious formation of PNNs in RTT. Further, we identify increased expression of HAPLN1 and other PNN / ECM components in the developing Mecp2-null cortex, and demonstrate that PNNs are structurally and biochemically mature at an earlier developmental stage. These results provide essential insight into the mechanisms and structure of aberrant PNNs in Mecp2-null cortex and identify potential new avenues for targeted rescue or reversal of the precocious closing of the critical period in RTT. | | 9:45a |
Experience-dependent reconfiguration of receptors at a sensory compartment regulates neuronal plasticity
Neurons continuously adjust their properties as a function of experience. Precise modulation of neuronal responses is achieved by multiple cellular mechanisms that operate over a range of timescales. Primary sensory neurons rapidly adapt their sensitivities via posttranslational mechanisms including regulated trafficking of sensory molecules but also alter their transcriptional profiles on longer timescales to adapt to persistent sensory stimuli. How diverse transcriptional and posttranscriptional pathways are coordinated in individual sensory neurons to accurately adjust their functions and drive behavioral plasticity is unclear. Here we show that temperature experience modulates both transcription and trafficking of thermoreceptors on different timescales in the C. elegans AFD thermosensory neurons to regulate response plasticity. Expression of the PY motif-containing adaptor protein (PYT-1) as well as the GCY-18 warm temperature-responsive guanylyl cyclase thermoreceptor is transcriptionally upregulated in AFD upon a temperature upshift. We find that as GCY-18 begins to accumulate at the AFD sensory endings, the GCY-23 cooler temperature-responsive thermoreceptor9 exhibits altered subcellular localization and increased retrograde trafficking, thereby increasing the functional GCY-18 to GCY-23 ratio in the AFD sensory compartment. Altered GCY-23 localization and trafficking requires PYT-1-dependent endocytosis, and we show that PYT-1-mediated modulation of the GCY-18 to GCY-23 protein ratio at the AFD sensory endings is necessary to shift the AFD response threshold towards warmer values following the temperature upshift. Our results describe a mechanism by which transcriptional and posttranscriptional mechanisms are temporally coordinated across sensory receptors to fine tune experience-dependent plasticity in the response of a single sensory neuron type. | | 2:46p |
Tunneling Nanotube-like Connections in the Developing Cerebellum: Distinct from Cytokinetic and Intercellular Bridges
Intercellular communication is essential for brain development. While classical communication modes-such as paracrine, juxtacrine and synaptic signaling-are well characterized, emerging evidence suggests that tunneling nanotubes (TNTs), membranous bridges primarily observed in vitro, may also contribute. However, their presence and function in vivo remain unclear, partly due to the challenge of distinguishing them from other types of intercellular connections (ICs). Building on prior evidence of ICs in the external granule layer (EGL) of the developing cerebellum, we investigated their nature in postnatal day 7 (P7) mice. Using immunofluorescence and genetically sparse labeling, we distinguished cytokinetic bridges (CBs), transient connections formed between daughter cells during the final stage of cell division, and intercellular bridges (IBs), more stable connections that persist after division, from TNT-like structures, which form independently of cell division. We observed CBs but not IBs in the EGL. We also observed TNT-like connections throughout the EGL, which appeared to connect both clonally and non-clonally related cells. The presence of these TNT-like structures in the developing EGL suggests that TNT-like connections may contribute to intercellular communication, paving the way for further study of a previously unrecognized mechanism that could influence neuronal fate, migration, and network formation during cerebellar development. |
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