Gordon Holmes syndrome (GHS) is a neurological disorder associated with neuroendocrine, cognitive, and motor impairments with corresponding neurodegeneration. Mutations in the E3 ubiquitin ligase RNF216 are strongly linked to GHS. Previous studies show that deletion of Rnf216 in mice led to sex-specific neuroendocrine dysfunction due to disruptions in the hypothalamic-pituitary-gonadal axis. To address RNF216 action in cognitive and motor functions, we tested Rnf216 knockout (KO) mice in a battery of motor and learning tasks for a duration of one year. Although male and female KO mice did not demonstrate prominent motor phenotypes, KO females displayed abnormal limb clasping. KO mice also showed age-dependent strategy and associative learning impairments with sex-dependent alterations of microglia in the hippocampus and cortex. Additionally, KO males but not females had more negative resting membrane potentials in the CA1 hippocampus without any changes in miniature excitatory postsynaptic current (mEPSC) ...

Voluntary motor control is thought to be predicated on the ability to efficiently integrate and process somatosensory afferent information. However, current approaches in the field of motor control have not factored in objective markers of how the brain tracks incoming somatosensory information. Here, we asked whether motor performance relates with such markers obtained with an analysis of the coupling between peripheral kinematics and cortical oscillations during continuous movements, best known as corticokinematic coherence (CKC). Motor performance was evaluated by measuring both gross and fine motor skills using the Box and Blocks Test (BBT) and the Purdue Pegboard Test (PPT), respectively, and with a biomechanics measure of coordination. Sixty-one participants completed the BBT, while equipped with electroencephalography and electromyography, and the PPT. We evaluated CKC, from the signals collected during the BBT, as the coherence between movement rhythmicity and brain activity, and coordination as th...

Declaring the 1990's as The Decade of the Brain put the field of neuroscience at the forefront of public attention, with the nervous system becoming a subject of increasing interest in popular media. Although this has generally brought large swaths of the public closer to neuroscience, most current research is published and disseminated in a single language: English. This is unsurprising as English is indeed the lingua franca in scientific circles, but people around the world communicate in many other languages. To make neuroscience accessible to a larger audience, we share an initiative to translate the Knowing Neurons platform into a second language: Spanish. This collaborative project integrates Humanities and STEM academic programs to make use of bilingual university students, in association with professional linguists and neuroscientists, to translate scientific content into a relatable format to Spanish speakers regardless of their country of origin. The translation effort was piloted within the fram...

Humans use tactile feedback to perform skillful manipulation. When tactile sensory feedback is unavailable, for instance, if the fingers are anesthetized, dexterity is severely impaired. Imaging the deformation of the finger pad skin when in contact with a transparent plate provides information about the tactile feedback received by the central nervous system. Indeed, skin deformations are transduced into neural signals by the mechanoreceptors of the finger pad skin. Understanding how this feedback is used for active object manipulation would improve our understanding of human dexterity. In this paper, we present a new device for imaging the skin of the finger pad of one finger during manipulation performed with a precision grip. The device’s mass (300 g) makes it easy to use during unconstrained dexterous manipulation. Using this device, we reproduced the experiment performed in Delhaye et al. 2021a. We extracted the strains aligned with the object’s movement, i.e., the vertical strains in the ulnar and r...

Stereotypical isocortical tau protein pathology along the Braak-Stages has been described as an instigator of neurodegeneration in Alzheimer's Disease (AD). Less is known about tau pathology in motor regions, although higher-order motor deficits such as praxis dysfunction are part of the clinical description. Here, we examined how tau pathology in cytoarchitectonically mapped regions of the primary and higher-order motor network in comparison to primary visual and sensory regions varies across the clinical spectrum of AD. We analyzed tau PET scans from the ADNI-cohort in patients with mild cognitive impairment (MCI; N  = 84) and dementia of the Alzheimer's Disease type (DAD; N  = 25). Additionally, an amyloid-negative sample of healthy older individuals (HC; N  = 26) were included. Standard-uptake ratio values (SUVR) were extracted in native space from the left and the right hemispheres. A repeated measurement analysis of variance was conducted to assess the effect of diagnostic disease category on tau pat...

Prefrontal cortex (PFC) intrahemispheric activity and the interhemispheric connection have a significant impact on neuropsychiatric disorder pathology. This study aimed to generate a functional map of FC intrahemispheric and interhemispheric connections. Functional dissection of mouse PFCs was performed using the voltage-sensitive dye (VSD) imaging method with high speed (1 ms/frame), high resolution (256 × 256 pixels), and a large field of view (∼10 mm). Acute serial 350 μm slices were prepared from the bregma covering the PFC and numbered 1–5 based on their distance from the bregma (i.e., 1.70, 1.34, 0.98, 0.62, and 0.26 mm) with reference to the Mouse Brain Atlas ([Paxinos and Franklin, 2008][1]). The neural response to electrical stimulation was measured at nine sites and then averaged, and a functional map of the propagation patterns was created. Intracortical propagation was observed in slices 3–5, encompassing the anterior cingulate cortex (ACC) and corpus callosum (CC). The activity reached area 33...

Acupuncture at Lianquan (CV23) acupoint has been shown to improve swallowing function in poststroke dysphagia (PSD). This improvement is supposed to be associated with the regulation of neuronal activity in the contralateral primary motor cortex (M1), while the underlying mechanism still needs to be elucidated. Perineuronal nets (PNNs) are well-known to be involved in the regulation of neuronal activity. Thus, we here aimed to detect the role of PNNs in the contralateral M1 hemisphere in the electroacupuncture (EA)-mediated effect in male mice. The results were obtained from a combination of methods, including in vitro slice electrophysiological recording, in vivo electrophysiological recording, and immunofluorescent staining in male mice. These results showed a decrease of the excitatory postsynaptic currents (sEPSCs) and no alteration of the inhibitory postsynaptic currents (sIPSCs) in the GABAergic neurons and the tonic inhibition in the excitatory neurons in the contralateral M1 after stroke induction,...

Transient receptor potential ankyrin 1 (TRPA1) is a polymodal cation channel that is activated by electrophilic irritants, oxidative stress, cold temperature, and GPCR signaling. TRPA1 expression has been primarily identified in subsets of nociceptive sensory afferents and is considered a target for future analgesics. Nevertheless, TRPA1 has been implicated in other cell types including keratinocytes, epithelium, enterochromaffin cells, endothelium, astrocytes, and CNS neurons. Here, we developed a knock-in mouse that expresses the recombinase FlpO in TRPA1-expressing cells. We crossed the TRPA1Flp mouse with the R26ai65f mouse that expresses tdTomato in a Flp-sensitive manner. We found tdTomato expression correlated well with TRPA1 mRNA expression and sensitivity to TRPA1 agonists in subsets of TRPV1 (transient receptor potential vanilloid receptor type 1)-expressing neurons in the vagal ganglia and dorsal root ganglia (DRGs), although tdTomato expression efficiency was limited in DRG. We observed tdTomat...

Antibody (Ab)-based imaging techniques rely on reagents whose performance may be application specific. Because commercial antibodies are validated for only a few purposes, users interested in other applications may have to perform extensive in-house antibody testing. Here, we present a novel application-specific proxy screening step to efficiently identify candidate antibodies for array tomography (AT), a serial section volume microscopy technique for high-dimensional quantitative analysis of the cellular proteome. To identify antibodies suitable for AT-based analysis of synapses in mammalian brain, we introduce a heterologous cell-based assay that simulates characteristic features of AT, such as chemical fixation and resin embedding that are likely to influence antibody binding. The assay was included into an initial screening strategy to generate monoclonal antibodies that can be used for AT. This approach simplifies the screening of candidate antibodies and has high predictive value for identifying anti...

Motivation plays a role when a listener needs to understand speech under acoustically demanding conditions. Previous work has demonstrated pupil-linked arousal being sensitive to both listening demands and motivational state during listening. It is less clear how motivational state affects the temporal evolution of the pupil size and its relation to subsequent behavior. We used an auditory gap detection task ( N  = 33) to study the joint impact of listening demand and motivational state on the pupil size response and examine its temporal evolution. Task difficulty and a listener’s motivational state were orthogonally manipulated through changes in gap duration and monetary reward prospect. We show that participants’ performance decreased with task difficulty, but that reward prospect enhanced performance under hard listening conditions. Pupil size increased with both increased task difficulty and higher reward prospect, and this reward prospect effect was largest under difficult listening conditions. Moreo...