Biology subjects

Yau, J.

Publications and source records attributed to Yau, J..

6 recordsLinked to original sources

bioRxiv2026

Enkephalin constrains fear learning via volume transmission to the lateral amygdala

Fear learning involves the formation of associations between cues and aversive outcomes, a process that must be tightly regulated to prevent excessive or generalised fear. Dopamine release in the lateral amygdala (LA) drives fear acquisition, whereas endogenous opioids constrain it. However, whether opioids are dynamically released within the amygdala circuits during learning, and how they exert this control remain unclear. Here we show that met-enkephalin is locally released within the amygdala during auditory fear conditioning, with signals shifting from the aversive outcome to its predictive cue as learning progresses. The amygdalo-striatal transition zone (ASt), is the principal source of this enkephalin, released from medium spiny neurons receiving strong auditory thalamic input. This enkephalin spreads from the ASt to the LA via volume transmission. Selective knockdown in the ASt abolished opioid signals and enhanced fear learning, demonstrating that this diffuse signal constrains fear memory formation. We further show that enkephalin suppresses dopamine release in both the ASt and LA via {micro}-opioid receptors, identifying the ASt as a neuromodulator hub coordinating opioid and dopaminergic signalling across amygdala fear circuits. Although demonstrated here for auditory fear learning, the ASt receives multimodal sensory input, suggesting a broader mechanism through which sensory experience recruits enkephalin release to gate associative learning

neuroscience↗

bioRxiv2026

Electrophysiological features of signals recorded from white matter

Intracranial neurophysiology studies have typically ignored signals from electrodes located in white matter (WM), assuming that their information content is artifactual or related to nearby gray matter (GM). Here, we tested the electrophysiological and functional features of signals recorded from different WM locations. Signals were recorded from 19 patients undergoing intracranial monitoring for drug-resistant epilepsy by means of stereo-electroencephalography (sEEG). Each sEEG electrode was classified into WM or GM based on the surrounding tissue. We obtained recordings from a total of 1,717 sEEG electrode contacts, 36% in WM, while the patients were in awake resting state (5 minutes). For each sEEG electrode, we employed a model-based spectral decomposition to separate periodic and aperiodic components, and we computed signal complexity metrics. For a subset of participants, we computed WM structural information from diffusion-weighted magnetic resonance imaging and we evaluated functional signals during a cognitive control task. Our results show that signals recorded from WM have different spectral features and higher complexity than GM. Complexity correlates positively with fractional anisotropy, and modulations related to behavior during the task were detected in WM. Overall, this indicates that WM signals carry information that may reflect signal propagation across WM fiber tracts.

neuroscience↗

bioRxiv2025

Prominent white matter related abnormalities associated with diverse molecular alterations in a mouse model of Col4a1 cerebral small vessel disease.

White matter abnormalities are a hallmark of cerebral small vessel disease (cSVD) and are closely linked to cognitive decline and dementia. However, despite their clinical importance, underlying mechanisms remain poorly understood. Collagen IV, encoded by genes COL4A1/COL4A2, is a major component of the basement membrane, a specialised extracellular matrix (ECM) structure. Mutations in these genes cause a genetic form of cSVD. We tested the hypothesis that ECM defects caused by a Col4a1 mutation lead to white matter pathology using an established mouse model of cSVD (Col4a1+/Svc). Behavioural testing with magnetic resonance diffusion tensor imaging, pathology and ultrastructural investigations of white matter were studied. The studies revealed that Col4a1+/Svc mice have cognitive impairments, reduced myelinating oligodendrocyte pools, axonal myelination defects, and altered white matter structural integrity. Proteomic analysis, of isolated white matter from Col4a1+/Svcmice, identified extensive changes to ECM composition and endoplasmic reticulum (ER) biology including ER stress induction. We also demonstrated that targeting protein folding to promote collagen secretion and reduce ER stress, increased myelinating oligodendrocytes and axon-glial integrity in Col4a1+/Svc mice. These data provide novel insight into the pathomolecular mechanisms of white matter abnormalities in cSVD and identify a modifiable pathway as a putative therapeutic target for cSVD.

neuroscience↗

bioRxiv2025

Reorganization of motor functions within visuomotor networks subsequent to somatosensory cortical damage

Somatosensory inputs are critical to motor control. Animal studies have shown that primary somatosensory lesions cause sensorimotor deficits along with disrupted organization in primary motor cortex (M1). How does damage in primary somatosensory cortex (S1) influence motor networks in humans? Using fMRI, we examined two individuals with extensive damage to left somatosensory cortex, but primarily intact motor cortex and preserved motor abilities. Given left S1 damage, tactile detection and localization were impaired for the contralesional hand in both individuals. When moving the contralesional hand, LS, with near complete damage to the S1 hand area, showed increased activation in ipsilesional putamen and deactivation in contralesional cerebellum relative to age-matched controls. These findings demonstrate influences of S1 damage to subcortical sensorimotor areas that are distant from the lesion site, and a potential reweighting of the motor network with increased action selection in putamen and inhibition of sensory prediction in cerebellum in the face of sensory loss. In contrast, RF, who had a small island of spared S1 in the hand area, showed greater activation in contralesional S1 for movement versus rest. This same region was also activated by pure somatosensory stimulation in a second experiment, suggesting that the spared S1 area in RF still subserves sensorimotor processing. Finally, the right middle occipital gyrus was more strongly activated in both individuals compared with controls, suggesting a potential reliance on visual imagery in the face of degraded sensory feedback.

neuroscience↗

bioRxiv2023

Acute loss of fingertip sensation leads to general compensatory changes in eye-hand coordination

The role of sensory feedback is well established in current models of motor control, evidenced by deficits in movement coordination resulting from impaired sensory function. When vision and touch are both available for object-oriented manual behaviors, these senses can be distinctly leveraged; vision guides movement planning while touch provides feedback on hand-object interactions. How eye-hand coordination changes with the loss of somatosensory feedback has not been well studied. Conceivably, vision is recruited to compensate for the feedback lost when touch is abolished. We tested healthy participants on a manual dexterity task, consisting of moving small metal pegs. The task was performed before and after administration of digital anesthesia that abolished cutaneous sensations while preserving motor function with the acting hand. During peg collection, transport, and placement epochs, we tracked gaze direction and hand positions while also recording forces applied to the pegboard. We hypothesized that the nervous system selectively adapts eye-hand coordination according to the dexterity demands of the task epochs. We found that participants maintained the ability to perform the pegboard task following the loss of cutaneous feedback, albeit with longer trial times and altered force profiles. Notably, somatosensory loss was accompanied by a shift in visual behavior marked by a closer alignment between gaze and hand positions during all task epochs, even those that did not involve object manipulation. Together, these data affirm the contributions of sensory feedback to force control in service of dexterous object manipulation and reveal the non-selective nature of compensatory eye-hand coordination processes. Significance StatementTouch and vision typically support distinct, but coordinated aspects of dexterous manual behaviors. Here, we evaluated how acute removal of tactile feedback using digital anesthesia affected performance and eye-hand coordination in a manual dexterity task. With insensate fingers and intact vision, participants continued to perform the task successfully, albeit with longer trial times and altered force profiles. We also observed closer alignment between gaze and hand positions during all task epochs, even those that did not involve object manipulation. Our results reveal the consequences of acute somatosensory loss and the general nature of compensatory eye-hand coordination processes.

neuroscience↗

bioRxiv2019

EPI distortion correction for simultaneous human brain stimulation and imaging at 3T

Transcranial magnetic stimulation (TMS) can be paired with functional magnetic resonance imaging (fMRI) in simultaneous TMS-fMRI experiments. These multimodal experiments enable causal probing of network architecture in the human brain which can complement alternative network mapping approaches. Critically, merely introducing the TMS coil into the scanner environment can sometimes produce substantial magnetic field inhomogeneities and spatial distortions which limit the utility of simultaneous TMS-fMRI. We assessed the efficacy of point spread function corrected echo planar imaging (PSF-EPI) in correcting for the field inhomogeneities associated with a TMS coil at 3T. In phantom and brain scans, we quantitatively compared the coil-induced distortion artifacts measured in PSF-EPI scans to artifacts measured in conventional echo-planar imaging (EPI) and a simultaneous multi-slice sequence (SMS)-EPI. While we observed substantial coil-related artifacts in the data produced by the conventional EPI and SMS sequences, PSF-EPI produced data that had significantly greater signal-to-noise and less distortions. In phantom scans with the PSF-EPI sequence, we also characterized the temporal profile of dynamic artifacts associated with TMS delivery and found that image quality remained high as long as the TMS pulse preceded the RF excitation pulses by at least 50ms. Lastly, we validated the PSF-EPI sequence in human brain scans involving TMS and motor behavior as well as resting state fMRI scans. Our collective results demonstrate the superiority of PSF-EPI over conventional EPI and SMS sequences for simultaneous TMS-fMRI when coil-related artifacts are a concern. The ability to collect high quality resting state fMRI data in the same session as the simultaneous TMS-fMRI experiment offers a unique opportunity to interrogate network architecture in the human brain.

neuroscience↗