bioRxiv Subject Collection: Neuroscience's Journal
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Wednesday, January 8th, 2025
| Time |
Event |
| 2:01a |
Locally induced traveling waves generate globally observable traveling waves
Cortical traveling waves have been proposed as a fundamental mechanism for neural communication and computation. Methodological uncertainties currently limit the interpretability of non-invasive, extracranial traveling wave data, sparking debates about their cortical origin. Studies using EEG or MEG typically report waves that cover large portions of the sensor array which are often interpreted as reflecting long range cortical waves. Meanwhile, invasive, intracranial recordings in humans and animals routinely find both local, mesoscopic waves and large scale, macroscopic waves in cortex. Whether the global sensor-array waves found with EEG/MEG necessarily correspond to macroscopic cortical waves or whether they are merely projections of local dynamics remains unclear. In this study, we made use of the well-established retinotopic organization of early visual cortex to generate traveling waves with known properties in human participants (N=19, m/f) via targeted visual stimulation, while simultaneously recording MEG and EEG. The inducer stimuli were designed to elicit waves whose traveling direction in mesoscopic retinotopic visual areas depends on stimulus direction, while leaving macroscopic activation patterns along the visual hierarchy largely unchanged. We observed that the preferred direction of traveling waves across the sensor array was influenced by that of the visual stimulus, but only at the stimulation frequency. Comparison between single-trial and trial-averaged responses further showed considerable temporal variation in traveling wave patterns across trials. Our results highlight that under tight experimental control, non-invasive, extracranial recordings can recover mesoscopic traveling wave activity, thus making them viable tools for the investigation of spatially constrained wave dynamics. | | 8:31a |
Nucleus accumbens dopamine encodes the trace period during appetitive Pavlovian conditioning
Pavlovian conditioning tasks have been used to identify the neural systems involved with learning cue-outcome relationships. In delay conditioning, the presentation of a conditioned stimulus (CS) overlaps or co-terminates with the delivery of the unconditioned stimulus (US). Prior studies demonstrate that behavioral responding during delay conditioning is regulated by dopamine signaling in the nucleus accumbens (NAc). In particular, the dopamine response to the CS reflects the relative value of the upcoming reward in these tasks. In contrast to delay conditioning, trace conditioning involves a trace period that separates the end of the CS and the delivery of the US. While dopamine has been implicated in trace conditioning, no studies to date have examined how NAc dopamine responds to reward-related stimuli in these tasks. To address this, we developed a within-subject trace conditioning task where distinct audio CSs signaled either a short trace period (5s) or a long trace period (55s) prior to the delivery of a food reward. Male rats exhibited higher levels of conditioned responding and a faster latency to respond to the Short Trace CS relative to the Long Trace CS. Voltammetry recordings in the NAc found that dopamine levels to the CS increased on Short Trace trials but decreased on Long Trace trials. Conversely, US-evoked dopamine responses were greater on Long Trace trials relative to Short Trace trials. We found that the CS dopamine response correlated with the latency to respond and not to the level of conditioned responding. Furthermore, the relationship between CS dopamine and latency was best explained by an exponential function. Taken together, our results illustrate how CS-evoked dopamine signals in the NAc relate to behavioral outcomes. Furthermore, we find that trace period is encoded by the bidirectional NAc dopamine response to the CS during Pavlovian conditioning.
Significance statementLearning how to associate a given cue with an outcome is fundamental process underlying reward seeking behavior. Dopamine in the ventral striatum is important for establishing the link between cues and rewarding outcomes in Pavlovian conditioning tasks. However, it is unclear how striatal dopamine release responds to cues during trace conditioning when there is temporal gap between the cue and the rewarding outcome. To address this, we performed voltammetry recordings of dopamine release in male rats trained on trace conditioning task. We demonstrate that cue-evoked dopamine signals encode the trace period and is related to the latency to respond. While prior reports find that the relative reward value is signaled by increases in dopamine neuron activity to cues, the current study highlights the that dopamine response to reward-predictive cues can signal the relative reward value through bidirectional changes in dopamine transmission. | | 8:31a |
Human cortical dynamics reflect graded contributions of local geometry and network topography
The brain is a physically embedded and heavily interconnected system that expresses neural rhythms across multiple time scales. While these dynamics result from the complex interplay of local and inter-regional factors, the relative contribution of such mechanisms across the cortex remains unclear. Our study explored geometric, microstructural, and connectome-level constraints on cortex-wide neural activity. We leveraged intracranial electroencephalography recordings to derive an intrinsic coordinate system of human cortical dynamics. Using multimodal neuroimaging, we could then demonstrate that these patterns were largely explainable by geometric properties indexed by inter-regional distance. However, dynamics in transmodal association regions were additionally explainable by incorporation of inter-regional microstructural similarity and connectivity information. Our findings were consistent when cross-referencing electroencephalography and imaging data from large-scale atlases and when using data obtained in the same individuals, suggesting subject-specificity and population-level generalizability. Together, our results support gradual shifts in the balance of local and macroscale constraints on cortical dynamics and highlight a key role of transmodal networks in inter-regional cortical coordination. | | 8:31a |
A stress-activated mid-insula to BNST pathway regulates susceptibility to abstinence-induced negative affect in female mice
Stress is central to many neuropsychiatric conditions, including alcohol use disorder (AUD). Stress influences the initiation and continued use of alcohol, the progression to AUD, and relapse. Identifying the neurocircuits activated during stress, and individual variability in these responses is critical for developing new treatment targets for AUD, particularly to mitigate stress-induced relapse. Using a longitudinal approach, this study examined the relationship between sub-chronic stress exposure and negative affect during protracted abstinence following chronic ethanol exposure. Sub-chronic restraint stress heightened negative affect-like behavior in protracted abstinence. Interestingly, this was driven by a subset of "stress-susceptible" female mice. We examined the mid-insula, a hub in the brains salience network, as a driver of this effect, given its role in emotional regulation and links to alcohol craving, consumption, and abstinence-induced negative affect. Mid-insula GCaMP fiber photometry revealed that GCaMP activity during stress exposure was positively correlated with activity during the novelty-suppressed feeding test (NSFT) two weeks into abstinence. A distinct subset of mice exhibited increasing activity during the consummatory phase, implicating the mid-insula as a neural basis for heightened negative affect in abstinence. Chemogenetic inhibition of mid-insula neurons projecting to the dorsal BNST during stress disrupted the emergence of stress susceptibility, highlighting this circuit as a key determinant of susceptibility to abstinence-induced negative affect. These outcomes were female-specific, addressing a critical gap in understanding AUD risk in women. Furthermore, female mice exhibited higher struggling behavior during stress than males. However, this effect was blocked by chemogenetic inhibition of the insula-BNST pathway during stress. By linking pre-alcohol stress response with abstinence outcomes, this work positions the insula-BNST pathway as a potential AUD circuit activity biomarker and therapeutic target. | | 8:31a |
Projecting neurons from lateral entorhinal cortex to basolateral amygdala mediate the encoding of incidental odor-taste associations
Daily choices are determined by prior direct or indirect associations between low-salience cues and reinforcers. In this study, we used a mouse odor-taste sensory preconditioning task combined with genetic, intersectional and chemogenetic approaches to identify a novel brain circuit involved in mediated learning. We found that neuronal projections from the lateral entorhinal cortex to the basolateral amygdala are engaged during low-salience stimuli associations, which is essential for mediated learning formation. | | 4:32p |
Specificity Protein 1 is essential for the limb trajectory of ephrin-mediated spinal motor axons
The precise organization of neural circuits requires highly specific axon guidance, facilitated by cell-surface guidance receptors on axonal growth cones that help neurons reach their target destinations. Despite a limited repertoire of known guidance receptors and ligands, neural systems achieve complex axonal networks, suggesting that additional regulatory mechanisms exist. One proposed strategy is the co-expression of ligands and their receptors on the same axons, allowing modulation of receptor responsiveness to guidance cues. To investigate this mechanism, we studied the spinal lateral motor column (LMC) motor neurons, which make a binary axon pathfinding decision toward limb targets. We hypothesized that specificity protein 1 (Sp1), a transcription factor, regulates ephrin expression in LMC neurons, thereby modulating receptor functions via cis-attenuation to ensure accurate axonal pathfinding. Our results show that Sp1 is indeed expressed in LMC neurons during critical axonal extension periods. Manipulating Sp1 activity disrupted LMC axon trajectory selection, and RNA-Seq analysis indicated that Sp1 regulates genes associated with axon guidance, including ephrins. We found that Sp1 knockdown affected ephrin/Eph cis-binding and trans-signaling, highlighting Sp1's role in controlling axonal projections through ephrin gene regulation. Additionally, coactivators p300 and CBP are essential for Sp1's regulatory function. These findings identify Sp1 as a key transcription factor in LMC neurons, essential for ephrin expression and ephrin/Eph-mediated axon guidance, providing insights into the molecular mechanisms of neural circuit formation. | | 8:00p |
Following the Robot's Lead: Predicting Human and Robot Movement from EEG in a Motor Learning HRI Task
Human-robot interaction (HRI) offers unique opportunities to study the neuroscience of human motor control through controlled and reproducible sensory stimuli. In this study, we introduce an innovative neuroscience-HRI framework inspired by the Serial Reaction Time (SRT) task, that combines EEG with a task where a humanoid robot performs preprogrammed movement sequences that are mirrored by a human participant in real time. The use of a humanoid robot ensures precise and repeatable sensory-motor stimuli in the 3D peripersonal space of the participant, providing experimental conditions that may be challenging to replicate with traditional methods. Behavioral performance is assessed by measuring the temporal lag between human and robot movements, which decreases with training, reflecting motor sequence learning. Concurrently, EEG data from the human participant is analyzed to reveal neural correlates of learning and movement dynamics. Event-Related Spectral Perturbations (ERSP) in theta, mu, and beta frequency bands demonstrate distinct patterns associated with rest, fixation, and movement. Furthermore, the ERSP changes over successive trials reflect the progression of sequence learning, highlighting the relationship between neural oscillations and motor learning. A Markov-Switching Linear Regression model further decodes EEG signals to predict movement parameters including both human and robot position and velocity in a time-resolved manner. Our findings highlight the potential of HRI as a robust platform for neuroscience research and underscore the value of EEG-based neural decoding in understanding motor sequence learning. This work suggests further advances for integrating robotics into neuroscience and rehabilitation research. | | 8:00p |
Behavioral and neural sound classification: Insights from natural and synthetic sounds
Throughout the course of a day, human listeners encounter an immense variety of sounds in their environment. These are quickly transformed into mental representations of objects and events that guide subsequent cognition and behavior in the world. Previous studies using behavioral and temporally resolved neuroimaging methods have demonstrated the importance of certain acoustic qualities for distinguishing among different classes of sounds during the early time period following sound onset (noisiness, spectral envelope, spectrotemporal change over time, and change in fundamental frequency over time). However, this evidence is largely based on correlational studies of natural sounds. Thus, two additional behavioral (Experiment 1) and EEG (Experiment 2) studies further tested these results using a set of synthesized stimuli (interspersed among a new set of natural sounds) that explicitly manipulated previously identified acoustic dimensions. In addition to finding similar correlational results as previous work (using new natural stimuli and tasks), classification results for the synthesized acoustic feature manipulations reinforced the importance of aperiodicity, spectral envelope, spectral variability and fundamental frequency change for representations of superordinate sound-categories. Analyses of the synthesized stimuli suggest that aperiodicity is a particularly robust cue in distinguishing some categories and that speech is difficult to characterize within this framework (i.e., using these acoustic dimensions and synthetic feature manipulations). These results provide a deeper understanding of the neural and perceptual dynamics that support the recognition of behaviorally important categories of sound in the time windows soon after sound onset. | | 8:33p |
Modeling the acutely injured brain environment in vitro.
A major challenge to study the regenerative potential of the injured brain is the limited access to this organ in vivo. To address this, we developed an innovative gliosis model that, although established in vitro, originates from a genuine injury in vivo. The model relies on reactive glia acquiring enhanced adhesion, facilitating their rapid adaptation to in vitro conditions, where it faithfully recapitulates key features of brain injury. These include a secretome associated with injury pathways, degenerative responses like neuronal death and neuroinflammation, and regenerative processes such as progenitor proliferation, recruitment and commitment to oligodendrocytes. Moreover, the exposure of adult glial cells to this culture medium recapitulates their acquisition of multipotency observed in both mouse and human injured brains. Finally, our approach allows studying glia-to-neuron reprogramming, a process challenging to tackle in vivo. Consequently, we present a novel tool for exploring stem cell dynamics and regenerative behaviors in CNS pathology. | | 11:19p |
2-Deoxy-D-glucose chemical exchange-sensitive spin-lock MRI of cerebral glucose metabolism after stroke in the rat
Rapid breakdown of cerebral glucose metabolism is a hallmark in stroke pathology. Metabolic activity delineates the penumbra from the infarct core, representing tissue that is potentially salvageable by therapeutic interventions. Tools to image dynamics of glucose and its spatial distribution could provide biomarkers of disease severity and of the success of therapeutic interventions. Here, we developed a new protocol to measure glucose metabolism in a rat model of stroke using chemical exchange-sensitive spin-lock (CESL) MRI of the glucose analog 2-deoxy-D-glucose (2DG). We further implemented a protocol that combines 2DG-CESL-MRI with cerebral blood flow (CBF) and diffusion MRI. We found that 2DG-CESL-MRI provides a biomarker of disturbed glucose metabolism after stroke with high effect to noise ratios. This is the first study to investigate CESL MRI of 2DG in the context of metabolism imaging in rodent stroke. | | 11:19p |
Eye metrics are a marker of visual conscious awareness and neural processing in cerebral blindness
Damage to the primary visual pathway can cause vision loss. Some cerebrally blind people retain degraded vision or sensations and can perform visually guided behaviors. These cases motivate investigation and debate on blind field conscious awareness and linked residual neural processing. A key challenge in this research is that subjective measures of blind field visual conscious awareness can be misleading. Alternatively, eye metrics, including pupil size and eye movements are promising objective markers of conscious awareness and brain activity. In this study, we examined stimulus-evoked changes in pupil size, blinking, and microsaccades in the sighted and blind field of cerebrally blind participants. Using standard analysis and innovative machine learning methods, our findings support that eye metrics can infer blind field conscious awareness, even when behavioral performance on a visual perception task indicated otherwise. Furthermore, these eye metrics were linked to blind field visual stimulus-evoked occipital cortical field potentials. These findings support recording eye metrics in cerebral blindness and highlight potential clinical applications, including tracking the recovery of conscious vision and visual neural processing. |
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