Neuroscience[JOURNAL]
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200 papers
The synaptic vesicle priming protein Munc13 mediates evoked somatodendritic dopamine release.
Lebowitz JJ, Banerjee A, Handy G … +2 more , Williams JT, Kaeser PS
J Neurosci · 2026 Jun · PMID 42362379 · Publisher ↗
Midbrain dopamine neurons release dopamine not only from their axons, but also from their somata and dendrites. Shared and distinct properties have been proposed for somatodendritic and axonal release, but the mechanisms...
Midbrain dopamine neurons release dopamine not only from their axons, but also from their somata and dendrites. Shared and distinct properties have been proposed for somatodendritic and axonal release, but the mechanisms of somatodendritic release remain unclear. We here used gene knockout, electrophysiology, and imaging to define roles of the synaptic vesicle priming protein Munc13 in somatodendritic dopamine release in comparison to axonal secretion. We characterized mice of either sex and found that Munc13 ablation decreased evoked but not spontaneous somatodendritic dopamine transmission measured as D2 receptor-mediated currents. Imaging with a fluorescent sensor confirmed the importance of Munc13 in evoked somatodendritic and axonal dopamine secretion. Pharmacological experiments revealed a modest contribution of release from norepinephrine axons to D2 receptor-mediated currents, and the relative contribution was enhanced after Munc13 knockout. Altogether, these data establish important roles for Munc13 in evoked somatodendritic release. These roles are similar to Munc13 functions in axonal dopamine release and at fast synapses. Spontaneous midbrain dopamine release was not impaired by Munc13 ablation from dopamine neurons and may rely on a release pathway that is independent of the prototypical release machinery employed at synapses. Neurons release neurotransmitter with high spatiotemporal precision from axonal nerve terminals. In addition, neurons also secrete transmitters such as monoamines, neurotrophins and neuropeptides from their somata and dendrites. While axonal release has been well characterized, less is known about mechanisms of somatodendritic secretion. The presented data establish that the synaptic vesicle priming protein Munc13 is important for evoked somatodendritic dopamine release. By contrast, spontaneous somatodendritic dopamine release is not affected by Munc13 ablation from dopamine neurons in the tested mouse mutants. The Munc13-dependence of evoked somatodendritic secretion supports the model of spatiotemporally precise signaling for this form of transmission. Spontaneous dopamine release may rely on a pathway that is independent of the classical neurotransmitter release machinery.
Speakers with cerebellar ataxia do not adapt speech segment durations in response to durationally altered auditory feedback.
Karlin R, Parrell B
J Neurosci · 2026 Jun · PMID 42362378 · Publisher ↗
Sensorimotor adaptation (motor learning) is crucial to maintain movement accuracy. This is particularly true for temporal control, as duration and initiation timing are perceived only after the movement, and thus cannot...
Sensorimotor adaptation (motor learning) is crucial to maintain movement accuracy. This is particularly true for temporal control, as duration and initiation timing are perceived only after the movement, and thus cannot benefit from mid-movement adjustments. The cerebellum is critical for both sensorimotor adaptation and various temporal functions, but its role in temporal adaptation has not been investigated. In this study, we examine the effect of cerebellar damage on temporal adaptation in speech, a natural but complex task that requires millisecond precision. We use an altered auditory feedback paradigm to extend the perceived duration of the vowel /ɛ/ in the word "best". Neurobiologically healthy controls (12 male, 22 female) adaptively shorten their vowels, but temporal adaptation is abolished in speakers with cerebellar damage (10 male, 24 female), who instead lengthen their vowels in response to the lengthening perturbation. This departs from findings in the spatial domain, where cerebellar damage merely reduces sensorimotor adaptation. A subset of speakers with cerebellar damage have lower perceptual acuity for vowel duration than controls; however, perceptual deficits did not drive the lack of adaptation. We suggest that temporal adaptation in speech is abolished due to cerebellar involvement in three aspects of temporal control: duration representation, temporal coordination, and temporal estimation. As speech motor control is highly complex, future research is needed to determine if the lack of adaptation observed in this study is due to combined demands on multiple cerebellar functions, or critical damage to a single function that is common to all temporal control. Speech is a complex motor activity that requires millisecond-level accuracy, thus providing a unique window to temporal control. When exposed to external perturbations that extend the perceived duration of vowels, speakers with cerebellar damage totally failed to adapt their speech to oppose the perturbation. Although a subset of speakers with cerebellar damage also had impaired perception of speech segment durations compared to controls, these perceptual deficits did not drive the lack of adaptation in the group. The total lack of adaptation departs from previous studies of sensorimotor adaptation in spatial control, and emphasizes the critical role of the cerebellum in maintaining accurate movement timing.
The precision of hippocampal representations predicts incremental value-learning across the adult lifespan.
van Geen C, Lempert KM, Cohen MS … +5 more , MacNear KA, Reckers FM, Zaneski L, Wolk DA, Kable JW
J Neurosci · 2026 Jun · PMID 42362377 · Publisher ↗
Correctly assigning value to different options and leveraging this information to guide choice is a cornerstone of adaptive decision-making. Reinforcement learning (RL) has provided a computational framework to study thi...
Correctly assigning value to different options and leveraging this information to guide choice is a cornerstone of adaptive decision-making. Reinforcement learning (RL) has provided a computational framework to study this process, and neural signals linked to RL have been identified in the striatum and medial prefrontal cortex. More recently, hippocampal contributions to this kind of value-learning have been proposed, at least under some conditions. Here, we test whether the hippocampus provides a signal of the option's identity that aids in credit assignment when learning about several perceptually similar items, and evaluate how this process differs across the lifespan. A sample of 251 younger and older adults (158F; 93M), including a subset (n=76) with simultaneous fMRI, completed an RL task in which they learned the value of four houses through trial-and-error. Older adults showed decreased accuracy, accompanied by reduced neural signaling of value at choice but not feedback. Using representational similarity analysis, we found that the precision with which choice options were represented in the posterior hippocampus during choice predicted accuracy across age groups. Despite previous evidence for neural de-differentiation with age, we found no support for a "blurring" of these stimulus representations in older adults. Rather, we observed reduced connectivity between the posterior hippocampus and the medial PFC in older adults, and this connectivity correlated with accuracy. Taken together, these findings identify a hippocampal contribution to incremental value learning, with age-related declines driven by reduced hippocampus-mPFC connectivity rather than a systematic change in the precision of hippocampal representations. Traditionally, the hippocampus has been linked to declarative memory, while reinforcement learning (RL) has been associated with striatal systems. Here, we challenge this dichotomy by showing that even simple trial-and-error RL depends on the hippocampus: the precision with which it represents perceptually similar choice options predicts choice accuracy across the lifespan. In older adults, we find that impairments in RL performance are not related to degraded hippocampal representations, but rather to reduced connectivity between the hippocampus and medial prefrontal cortex. These findings support a more integrated view of decision-making in which mnemonic and value-based systems interact even in basic learning contexts, and highlight age-related disruptions in the transfer of information across brain regions.
Accelerated long-term forgetting and relevant biomarkers for early detection in preclinical Alzheimer's disease.
Ohno M
Neuroscience · 2026 Jun · PMID 42362042 · Publisher ↗
Alzheimer's disease (AD) commences with the preclinical stage where individuals remain cognitively unimpaired but already have AD pathology. As fluid and neuroimaging biomarker research progresses, AD has become defined...
Alzheimer's disease (AD) commences with the preclinical stage where individuals remain cognitively unimpaired but already have AD pathology. As fluid and neuroimaging biomarker research progresses, AD has become defined biologically rather than based on traditional clinical symptoms. While the diagnosis of AD has been conceptually advanced by the AT(N) classification framework according to core biomarker profiles of amyloid-β (A), tau (T) and neurodegeneration (N), solely relying on biological diagnosis at an asymptomatic stage has limitations with potential ethical and psychosocial issues. Accelerated long-term forgetting (ALF) characterized by higher forgetting rates over longer delays (a week to months) captures substantial interest as one of the sensitive mnemonic measures. Remarkably, ALF assays have been increasingly applied to detecting subtle cognitive declines in preclinical AD individuals who are still normal on standard memory tests, which typically use ∼ 30 min delays to assess classical hippocampal amnesia. The findings suggest that ALF may reflect the impairment of systems memory consolidation, a process that is required to gradually transform memory traces temporarily stored in the hippocampus into cortical networks for long-term storage. This review provides an overview of recent progress in ALF research including the underlying mechanisms and fluid-based or brain imaging biomarkers, which have been explored not only in individuals at risk for developing AD but also in relevant animal models. The findings have important implications for how we can optimize the earlier and precise identification of patients at a preclinical stage of AD that is essential for designing effective preventive interventions.
Deciphering key factors contributing to age-related decline in visuomotor tracking through the manipulation of target refresh rate and gaze contingency.
Coudiere A, Michon J, Danion FR
Neuroscience · 2026 Jun · PMID 42362041 · Publisher ↗
The ability to continuously adjust hand movements using visual information is critical for success in many everyday tasks. To further characterize the age-related decline in visuomotor processes, here we investigated a t...
The ability to continuously adjust hand movements using visual information is critical for success in many everyday tasks. To further characterize the age-related decline in visuomotor processes, here we investigated a task in which participants had to track with the hand, by means of a joystick, a visual target whose position was updated at different rates on a screen (from 1.5 to 240 Hz). This procedure was selected to grade the necessity for online control. As the target refresh rate increased, the need to continuously update hand motor commands became greater. We also manipulated gaze contingency and asked participants to perform this tracking task under gaze-free and gaze-fixed conditions, a procedure chosen to assess the contribution of eye movements and peripheral vision. The comparison between 30 older (71 yrs, 17 females) and 28 younger (21 yrs, 17 females) participants revealed detrimental effects of aging on tracking accuracy, notably through greater mean cursor-target distance and lag. Importantly, temporally realigning hand and target signals did not erase the gap in tracking performance between young and older participants. Moreover, we noticed that the effect of age was greater under higher target refresh rates and gaze-free conditions. Finally, sex/gender differences were found in each age group with men generally outperforming women. Overall, we interpret these observations as evidence that the age-related decline in manual tracking is driven by both slower and less accurate visuomotor loops, particularly when eye movements are engaged.
LPI alleviates Alzheimer's disease pathology via the GPR55 receptor.
Xu W, Cao J, Liu Y … +7 more , Wei Z, Zha X, Xie S, Liu X, Wang W, Zhang C, Alzheimer’s Disease Neuroimaging Initiative (ADNI)
Neuroscience · 2026 Jun · PMID 42362040 · Publisher ↗
Lysophosphatidylinositol (LPI) is an endogenous GPR55 agonist, yet its role in Alzheimer's disease (AD) remains unclear. Here, we performed serum metabolomic profiling in 5xFAD mice and observed a reduction in multiple L...
Lysophosphatidylinositol (LPI) is an endogenous GPR55 agonist, yet its role in Alzheimer's disease (AD) remains unclear. Here, we performed serum metabolomic profiling in 5xFAD mice and observed a reduction in multiple LPI species prior to the onset of overt Aβ pathology, and this decrease was further corroborated in human cohort samples. Exogenous LPI treatment reduced cerebral Aβ deposition, improved performance in learning and memory behavioral tasks, reduced pathological microglial aggregation, inhibited astrocyte proliferation, and ameliorated hippocampal oxidative stress. Mechanistically, administration of the GPR55 antagonist ML191 blocked the protective effects of LPI, while the GPR55 agonist O-1602 recapitulated these benefits, indicating that LPI acts through GPR55. Collectively, our findings suggest that reduced LPI represents an early metabolic vulnerability in the 5xFAD model and establish the LPI-GPR55 axis as a potential therapeutic target for early intervention in AD.
DBS: from neuromodulation to neuroremodelling.
Lind V, Zrinzo L, Akram H
Nat Neurosci · 2026 Jun · PMID 42350817 · Publisher ↗
Abstract loading — click title to view on PubMed.
Human hippocampal ripples tune cortical responses based on predicted uncertainty.
Frank D, Moratti S, Hellerstedt R … +9 more , Sarnthein J, Li N, Horn A, Imbach L, Stieglitz L, Gil-Nagel A, Toledano R, Friston KJ, Strange BA
Nat Neurosci · 2026 Jun · PMID 42350816 · Publisher ↗
To encode information efficiently, our perceptual system should detect when situations are unpredictable (that is, informative) and modulate brain dynamics to prepare for encoding. Under uncertainty, there is an increase...
To encode information efficiently, our perceptual system should detect when situations are unpredictable (that is, informative) and modulate brain dynamics to prepare for encoding. Under uncertainty, there is an increased need to generate predictions about upcoming information, a process that has been proposed to require coordinated activity between the hippocampus and neocortex. Here we show, with direct recordings from the human hippocampus and visual cortex, that after exposure to unpredictable visual stimulus streams, hippocampal ripple activity increases in frequency and duration before stimulus presentation. Prestimulus hippocampal ripples suppress changes in visual cortex gamma activity associated with uncertainty and modulate poststimulus prediction error gamma responses in higher-level visual cortex to surprising stimuli. We reveal a function of hippocampal ripples in facilitating the propagation of visual stimuli based on the expected information gain. These results, therefore, link hippocampal ripples with predictive coding accounts of neuronal message passing and precision-weighted prediction errors, revealing a mechanism relevant for perceptual synthesis and subsequent memory encoding.
Learning shapes neural geometry in the primate prefrontal cortex.
Wójcik MJ, Stroud JP, Wasmuht D … +8 more , Kusunoki M, Kadohisa M, Buckley MJ, Costa RP, Myers NE, Hunt LT, Duncan J, Stokes MG
Nat Neurosci · 2026 Jun · PMID 42350815 · Publisher ↗
The relationship between the geometry of neural representations and the task being performed is a central question in neuroscience. The primate prefrontal cortex (PFC) is a primary focus of inquiry, as it can encode info...
The relationship between the geometry of neural representations and the task being performed is a central question in neuroscience. The primate prefrontal cortex (PFC) is a primary focus of inquiry, as it can encode information with geometries that either rely on past experience or are experience agnostic. One hypothesis is that PFC representations should evolve with learning, from a format that supports exploration of all possible task rules to a format that minimizes the encoding of task-irrelevant features and supports generalization. Here we test this idea by recording neural activity from the macaque PFC when learning a new rule ('XOR rule') from scratch. We show that PFC representations progress from being high dimensional, nonlinear and randomly mixed to low dimensional and rule selective. Upon generalizing the rule to new stimuli, these representations further evolve into an abstract, stimulus-invariant geometry. These findings reconcile previously conflicting accounts of PFC function by demonstrating how neural representations adapt across distinct stages of learning.
Blood-brain barrier dysfunction in surgery and anesthesia: a potential mechanistic contributor to postoperative cognitive dysfunction.
Alwesabi AK, Gao B, Xie J … +4 more , Yang B, Xie J, Ma Y, Liu Y
Neuroscience · 2026 Jun · PMID 42349542 · Publisher ↗
The blood-brain barrier (BBB) is essential for maintaining central nervous system homeostasis by regulating selective permeability and protecting neural tissue. Surgical interventions and anesthesia can compromise BBB in...
The blood-brain barrier (BBB) is essential for maintaining central nervous system homeostasis by regulating selective permeability and protecting neural tissue. Surgical interventions and anesthesia can compromise BBB integrity, particularly in elderly patients, contributing to postoperative cognitive dysfunction (POCD). This narrative review provides a BBB-centered perspective on postoperative cognitive dysfunction by critically evaluating blood-brain barrier dysfunction as a potential unifying mechanistic pathway linking surgical stress, systemic inflammation, anesthetic exposure, neuroinflammation, and cognitive decline. While previous reviews have examined these perioperative factors individually, this review integrates current experimental and clinical evidence to highlight BBB disruption as a central contributor to postoperative neurocognitive impairment and discusses its translational implications for perioperative neuroprotection. Surgical trauma triggers an acute inflammatory response with elevated cytokines, increasing BBB permeability and facilitating the entry of neurotoxic substances into the brain, thereby promoting neuroinflammation. Anesthetic agents may further exacerbate these effects. Emerging evidence suggests that BBB dysfunction may represent an important mechanistic contributor linking perioperative stress, neuroinflammation, and cognitive impairment; however, direct evidence establishing causality in humans remains limited. Interventions targeting BBB stabilization and perioperative neuroprotection may represent promising strategies to reduce the risk of POCD. A better understanding of these mechanisms is crucial for developing strategies to preserve cognitive function and improve postoperative outcomes. However, much of the current evidence is derived from preclinical studies, and direct causal relationships in humans remain limited. Future research should clarify neuroinflammatory pathways and identify effective protective therapies.
rno-miR-199a-3p-Nedd4 signaling regulates mast cell-dependent peripheral sensitization in osteoarthritis pain.
Liu B, Chen Z, Luo X … +11 more , Jiang Y, Li Z, Zheng Q, Huang J, Jiang H, He Y, Zeng L, Lim HY, Cai D, Qi W, Liang F
Neuroscience · 2026 Jun · PMID 42349541 · Publisher ↗
PURPOSE: Acupoints are fundamental to the efficacy of acupuncture. When the body is diseased, the pressure pain threshold (PPT) of the corresponding acupoints typically exhibits significant changes. Clinically, selecting...
PURPOSE: Acupoints are fundamental to the efficacy of acupuncture. When the body is diseased, the pressure pain threshold (PPT) of the corresponding acupoints typically exhibits significant changes. Clinically, selecting acupoints with marked PPT changes often enhances therapeutic efficacy. Mast cells are involved in changes in the PPT at acupoints, but the regulatory mechanism remains unclear. We aimed to identify microRNAs (miRNAs) that regulate mast cells to elucidate the mechanisms underlying PPT changes, thereby guiding clinical acupuncture practice. METHODS: We evaluated changes in PPT and differentially expressed miRNAs at the ST36 acupoint in a rat model of knee osteoarthritis. miRNA agonists and antagonists were injected to observe changes in the PPT at the ST36 acupoint. Subsequently, the functions of differentially expressed miRNA in regulating degranulation and their possible targets of action were evaluated using in vitro and in vivo experiments. RESULTS: PPT decreased in knee osteoarthritis (KOA) rats, accompanied by increased degranulation of local skin mast cells. rno-miR-199a-3p played a key role in this process. Overexpression of rno-miR-199a-3p increased mast cell degranulation. Furthermore, the overexpression of neural precursor cell expressed developmentally down-regulated 4 (Nedd4) is suppressed by rno-miR-199a-3p, which modulated mast cells. CONCLUSION: Pathological changes in the body lead to changes in the PPT, manifested by altered local pain thresholds and mast cell degranulation. rno-miR-199a-3p targets Nedd4, leading to mast cell degranulation, which probably underlies this mechanism.
Disrupted brain functional network topology and potential network reorganization in early-stage Parkinson's disease with probable REM sleep behavior disorder.
Huang C, Tan C, Shen Q … +8 more , Liu Q, Cai S, Niu Y, Lin Y, Deng S, Qiu Z, Zheng Z, Liao H
Neuroscience · 2026 Jun · PMID 42349540 · Publisher ↗
PURPOSE: Parkinson's disease with rapid eye movement sleep behavior disorder(RBD) often represents a more aggressive subtype, presenting more serious clinical manifestations even in early-stage disease. However, this sub...
PURPOSE: Parkinson's disease with rapid eye movement sleep behavior disorder(RBD) often represents a more aggressive subtype, presenting more serious clinical manifestations even in early-stage disease. However, this subtype's specific whole-brain functional network alterations in the early stages of the disease remain unclear. Research was designed to explore the unique functional network alterations patterns in early PD with RBD and underlying abnormal neural network development mechanisms. METHOD: We gathered resting-state fMRI data of35 healthy controls (HC), 33 early PD with probable RBD (PD + pRBD), and 32 early PD without RBD (PD-RBD). We utilized graph theory along with network-based methods to analyze the data. Research was conducted on correlations between network indicators and clinical scores. RESULT: PD + pRBD exhibited significantly decreased local efficiency than PD-RBD (p = 0.031). Compared to HC, PD + pRBD demonstrated more severe network disruptions than PD-RBD, after FDR correction, including significantly reduced small-world properties (p = 0.003), more widespread nodal alterations (p < 0.05), and extensive functional connectivity disruptions (p < 0.05). Modular analysis revealed functional network connectivity abnormalities within and between multiple networks, characterized by concurrent reductions and abnormal enhancements in functional connectivity. CONCLUSION: Early PD + pRBD exhibit specific and more severe neurofunctional network impairment pattern. Characterized by more significantly disrupted neurofunctional network topology and widespread functional connectivity abnormalities across multiple brain networks, with potential functional network reorganization. These functioning abnormalities may serve as imaging biomarkers for this clinically malignant subtype and provide potential neurobiological mechanism for understanding its poorer clinical phenotype.
Non-redundant role of the α3 isoform of Na,K-ATPase in neuronal excitability and spiking dynamics.
Reshetnikov K, Tiselko V, Dobretsov M
Neuroscience · 2026 Jun · PMID 42349539 · Publisher ↗
The Na,K-ATPase (NKA) is essential for neuronal excitability. The neuron-specific α3 isoform differs from the ubiquitous α1 isoform by its low affinity for intracellular Na, weak voltage dependence, and slightly reduced...
The Na,K-ATPase (NKA) is essential for neuronal excitability. The neuron-specific α3 isoform differs from the ubiquitous α1 isoform by its low affinity for intracellular Na, weak voltage dependence, and slightly reduced ATP sensitivity, yet the functional relevance of these features remains unclear. Using biophysically detailed models of stretch receptor neurons, we examined how isoform-specific pump kinetics influence firing behavior. Substitution of α1 for α3 NKA abolished sustained spike trains and reduced high-frequency entrainment. In contrast, modifying α3 NKA to exhibit α1-like voltage or ATP dependence did not affect neuronal excitability. These results indicate that Na affinity, rather than voltage or ATP dependence, is the critical determinant of α3 NKA specialization. Our findings provide a mechanistic explanation for the selective expression of α3 NKA in muscle spindle afferents and other high-frequency neurons, highlighting that NKA isoform properties are tuned to the discharge demands of distinct neuronal populations.
Using combined ROC curves to improve the diagnostic usefulness of glutaminase, prostaglandins, and 8-isoprostane as biomarkers of autism spectrum disorders;Role in the Glu-GABA-Gln cycle.
El-Ansary A, Alfawaz HA, Alhakbany M … +3 more , Bhat RS, Bjørklund G, Al-Ayadhi LY
BMC Neurosci · 2026 Jun · PMID 42343199 · Full text
Due to delayed symptoms and dependence of behavioral assessment, early diagnosis of autism spectrum disorder remains challenging. Identification of multivariate biomarker for the etiological mechanisms of ASD may enhance...
Due to delayed symptoms and dependence of behavioral assessment, early diagnosis of autism spectrum disorder remains challenging. Identification of multivariate biomarker for the etiological mechanisms of ASD may enhance diagnostic accuracy. Multivariable logistic regression combines many predictors into a single risk score (linear predictor), resulting in an optimised ROC curve that enhances diagnostic accuracy over individual markers. The method comprises modelling a binary result, determining the likelihood, and visualising ROC based on the projected probabilities, which often improves individual marker AUCs. In the present study a diagnostic performance for a biomarker panel reflecting glutamatergic dysfunction, oxidative stress, and neuroinflammation was evaluated. Plasma levels of glutaminase, 8-isoprostane, and prostaglandin E₂ (PGE₂) obtained from 44 children with ASD and 40 age-matched controls were evaluated using receiver operating characteristic (ROC) analysis, both individually and in combined ROC models. Glutaminase showed significant negative correlations with both 8-isoprostane and PGE₂, whereas a positive correlation was observed between 8-isoprostane and PGE₂. All the three-biomarker showed good diagnostic performance for ASD on its own with statistically significant (p = 0.001) values of AUC of 0.830 for glutaminase, AUC of 0.815 for 8-Isoprostane and AUC of 0.818 for PGE₂. However combined ROC modeling substantially improved diagnostic accuracy by achieving high apparent discriminative performance with AUC value of 0.977 with 92.3% sensitivity and 100.0% specificity. In conclusion, the diagnostic usefulness of independent glutaminase, 8-isoprostane, and prostaglandin E₂ (PGE₂) biomarkers may be enhanced by combining ROC. Combined markers show strong apparent discriminating power in a case-control method, but estimates are biassed towards optimism and are not diagnostic. Comprehensive assay validation, calibration, and clinically representative cohorts (including females and relevant differentials) are required for replication.
Brain-spleen axis regulates learned fear.
Whalley K
Nat Rev Neurosci · 2026 Jun · PMID 42342894 · Publisher ↗
Abstract loading — click title to view on PubMed.
Cell atlas of brain aneurysms reveals fibroblast-macrophage crosstalk.
Nat Neurosci · 2026 Jun · PMID 42342853 · Publisher ↗
Abstract loading — click title to view on PubMed.
Dynamic Sensorimotor Behavior Reveals Bayesian Belief Updating.
Britt N
J Neurosci · 2026 Jun · PMID 42342447 · Full text
Abstract loading — click title to view on PubMed.
Evolving Roles of Primary Cilia in CNS Development and Neural Circuit Function: From Human Disease to Molecular Underpinnings.
Noble AR, Doherty D, Stoeckli E … +1 more , Bachmann-Gagescu R
J Neurosci · 2026 Jun · PMID 42342446 · Full text
Primary cilia are small organelles acting as cellular antennae that sense and transduce diverse signals, including developmental signaling pathways in the developing central nervous system (CNS). This signaling is essent...
Primary cilia are small organelles acting as cellular antennae that sense and transduce diverse signals, including developmental signaling pathways in the developing central nervous system (CNS). This signaling is essential for normal CNS development, as evidenced by the prevalence of neurodevelopmental phenotypes in conditions arising from primary cilia dysfunction (ciliopathies). Though significant research has focused on the roles of primary cilia during CNS development, the functions of primary cilia in the mature CNS have only recently become a focus of investigation. Primary cilia are present on most vertebrate cells, including mature neurons and astrocytes and reportedly localize G-protein-coupled receptors, voltage-gated ion channels, and even synaptic proteins. Moreover, recent evidence highlights the dense "contactome" of cilia in the brain with adjacent neuronal structures and has even identified axo-ciliary synapses. Primary cilia are therefore both perfectly equipped and positioned to participate in regulating mature neural circuits. Consistent with these observations, primary cilia have also been linked to neurological and psychiatric symptoms without underlying brain malformations, both in ciliopathies and in nonciliopathy neurological conditions like autism spectrum disorder and schizophrenia. In this review, we bridge insights from human disease to evidence gained from animal and cell models to highlight the evolving roles of primary cilia in the developing and mature CNS. Primary cilia in the developing brain act as classical cellular antennae sensing secreted ligands, while primary cilia in the mature brain may also be capable of contact-dependent signaling, indicating a potential shift in the signaling capacity of primary cilia in the CNS.
Targeting of RhoA-ROCK pathway activators and linked molecular signaling in Alzheimer's disease: The paving dawn for future therapy.
Al-Kuraishy HM, Fahad EH, Jabir MS … +5 more , Rafeeq MF, Sulaiman GM, Amara IB, Albuhadily AK, Al-Gareeb AI
Neuroscience · 2026 Jun · PMID 42342024 · Publisher ↗
Rho-associated protein kinase (ROCK) is a serine/threonine kinase that plays a central role in regulating cellular processes, including growth, proliferation, survival, and migration. ROCK exists as two isoforms, ROCK1 a...
Rho-associated protein kinase (ROCK) is a serine/threonine kinase that plays a central role in regulating cellular processes, including growth, proliferation, survival, and migration. ROCK exists as two isoforms, ROCK1 and ROCK2, which function as the principal downstream effectors of Rho GTPases. Activation of the RhoA-ROCK signaling pathway is induced by a variety of extracellular stimuli, including angiotensin II (Ang II), platelet-derived growth factor (PDGF), integrins, and vascular endothelial growth factor (VEGF). RhoA-ROCK pathway promotes the production of amyloid beta (Aβ) and increases the formation of neurofibrillary tangles (NFTs) the hallmarks of Alzheimer's disease (AD). It has been shown that Rho-kinase inhibitors are effective against AD neuropathology and other neurodegenerative diseases through modulation of synaptic activity and neuroinflammation. To date, no clinical trials have directly evaluated the efficacy and safety of ROCK inhibitors in patients with AD. This gap highlights the need to explore alternative therapeutic strategies within the RhoA-ROCK signaling axis. In particular, targeting upstream activators of this pathway such as angiotensin II (Ang II), platelet-derived growth factor (PDGF), vascular endothelial growth factor (VEGF), and integrin may represent a more conceivable approach to attenuate AD-related neuropathology. Modulation of these signaling inputs has the potential to suppress the aberrant RhoA-ROCK activation and its downstream pathological consequences. Accordingly, this review aims to elucidate the mechanistic role of the RhoA-ROCK pathway in AD, and to critically examine the therapeutic potential targeting its upstream activators as a therapeutic strategy for AD.
Explorative investigation on effects of multi-day neurofeedback with implanted electrodes in patients with Parkinson's disease.
Rohr-Fukuma M, Stieglitz LH, Bujan B … +3 more , Imbach LL, Gassert R, Bichsel O
Neuroscience · 2026 Jun · PMID 42342023 · Publisher ↗
Neurofeedback, which consists of recording and visualizing neural activity in real-time, is a method currently being investigated as a supplementary treatment for Parkinson's disease (PD). By using implanted deep brain s...
Neurofeedback, which consists of recording and visualizing neural activity in real-time, is a method currently being investigated as a supplementary treatment for Parkinson's disease (PD). By using implanted deep brain stimulation (DBS) electrodes with interleaved sensing capability, previous studies have demonstrated the efficacy of neurofeedback based on beta oscillations in the basal ganglia. Herein, for the first time, we explored short-term neurofeedback ability over the course of multiple sessions with a fully implanted DBS system. Eight patients with PD participated in the study. Neurofeedback was established with a fully internalized DBS system using beta oscillations (13-35 Hz, exceptions at 12.7 Hz and 8.78 Hz) from the subthalamic nucleus as visual feedback. Down- and upregulation tasks were performed. Three sessions were conducted on separate days. Neurofeedback induced a significant decline in beta power in the first and third session, while the regulation ability was less pronounced in the second session. In an explorative analysis, an increase in dopaminergic medication induced deterioration of downregulation performance, while stimulation improved the downregulation ability. Changes in the power of gamma oscillations were also induced through beta oscillation neurofeedback, further implying pro-kinetic changes through neurofeedback. This study demonstrated the feasibility of multiple sessions of neurofeedback training with a fully implanted DBS system over several days, however a significant improvement over the cumulative sessions remained absent. Our explorative investigation on possible influencing factors indicates potential improvements of the experimental setup and motivates the use of DBS electrode-guided neurofeedback over extended periods and possibly in an outpatient setting.
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