Orexins, which are produced within neurons of the lateral hypothalamic area, play a pivotal role in the regulation of various behaviors, including sleep/wakefulness, reward behavior, and energy metabolism, via orexin receptor type 1 (OX1R) and type 2 (OX2R). Despite the advanced understanding of orexinergic regulation of behavior at the circuit level, the precise distribution of orexin receptors in the brain remains unknown. Here, we develop a new branched in situ hybridization chain reaction (bHCR) technique to visualize multiple target mRNAs in a semiquantitative manner, combined with immunohistochemistry, which provided comprehensive distribution of orexin receptor mRNA and neuron subtypes expressing orexin receptors in mouse brains. Only a limited number of cells expressing both Ox1r and Ox2r were observed in specific brain regions, such as the dorsal raphe nucleus and ventromedial hypothalamic nucleus. In many brain regions, Ox1r -expressing cells and Ox2r -expressing cells belong to different cell ty...

NMDA receptors (NMDARs) modulate glutamatergic excitatory tone in the brain via two complementary modalities: a phasic excitatory postsynaptic current and a tonic extrasynaptic modality. Here, we demonstrated that the tonic extrasynaptic NMDAR- current (INMDA) mediated by NR2A-containing NMDARs is an efficient biosensor detecting the altered ambient glutamate level in the supraoptic nucleus (SON). INMDA of magnocellular neurosecretory cells (MNCs) measured by nonselective NMDARs antagonist, AP5, at holding potential (Vholding) -70 mV in low concentration of ECF Mg2+ ([Mg2+]o) was transiently but significantly increased 1-week post induction of a DOCA (deoxycorticosterone) -salt hypertensive model rat. The INMDA uncovered by AP5 was compatible with that induced by a NR2A-selective antagonist, PEAQX (IPEAQX) in both DOCA-H2O (animals receive normal water after DOCA) and DOCA-salt (animals receive a mixture of 0.8% NaCl and 0.2% KCl in water after DOCA) groups. In agreement, NR2B antagonist, ifenprodil, or NR...

We have developed an open-source software for neuroscientists to analyze electrophysiological recordings. Named SimplyFire, the software gives the users the flexibility to analyze a variety of recordings using an interactive graphical user interface or as an importable Python package. The software features a simple plug-in structure that allows users to create and deploy various electrophysiology analysis tools. SimplyFire is prepackaged with tools commonly used in electrophysiology, such as noise filtering, trace averaging, miniature analysis, and trace exporting. We discuss in detail the algorithm behind different features of the analysis tool. We provide verification of the accuracy of the algorithm by testing the software using computer-generated traces with known true values of the events. SimplyFire will be distributed under the GPLv3.0 license. The open nature of this software will allow interested investigators to modify and expand the software for additional capabilities as needed. We believe this...

Lumbar erector spinae (LES) contribute to spine postural and voluntary control. Transcranial magnetic stimulation (TMS) preferentially depolarizes different neural circuits depending on the direction of electrical currents evoked in the brain. Based on recent evidence, posteroanterior current (PA-TMS) and anteroposterior (AP-TMS) current would respectively depolarize neurons in the primary motor cortex (M1) and the premotor cortex. These regions may contribute differently to LES control. This study examined whether responses evoked by PA- and AP-TMS are different during the preparation and execution of LES voluntary and postural tasks. Participants performed a reaction time task. A Warning signal indicated to prepare to flex shoulders (postural, n=15) or to tilt the pelvis (voluntary, n=13) at the Go signal. Single- and paired-pulse TMS (short-interval intracortical inhibition - SICI) were applied using PA- and AP-TMS before the Warning signal (baseline), between the Warning and Go signals (preparation) o...

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 Alzheimer's Disease Neuroimaging Initiative (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 (SUVRs) were extracted in native space from the left and the right hemispheres. A repeated measurement analysis of variance was conducted to assess the e...

The well-known arcuate fasciculus that connects the posterior superior temporal region with the language production region in the ventrolateral frontal cortex constitutes the classic peri-Sylvian dorsal stream of language. A second temporofrontal white matter tract connects ventrally the anterior to intermediate lateral temporal cortex with frontal areas via the extreme capsule. This temporofrontal extreme capsule fasciculus (TFexcF) constitutes the ventral stream of language processing. The precise origin, course, and termination of this pathway has been examined in invasive tract tracing studies in macaque monkeys, but there have been no standard protocols for its reconstruction in the human brain using diffusion imaging tractography. Here we provide a protocol for the dissection of the TFexcF in vivo in the human brain using diffusion magnetic resonance imaging (MRI) tractography which provides a solid basis for exploring its functional role. A key finding of the current dissection protocol is the demon...

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 to 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. A total of 61 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 ...

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 knock-out (KO) mice in a battery of motor and learning tasks for a duration of 1 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) f...

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. (2021)][1]. We extracted the strains aligned with the object’s movement, i.e., the vertical strains in the ulnar...

Our previous studies find that subcutaneously administered (s.c.) subanesthetic ketamine promotes sustained cortical disinhibition and plasticity in adult mouse binocular visual cortex (bV1). We hypothesized that intranasal delivery (i.n.) of subanesthetic ketamine may have similar actions. To test this, we delivered ketamine (10 mg/kg, i.n.) to adult mice and then recorded excitatory pyramidal neurons or PV+ interneurons in L2/3 of bV1 slices. In pyramidal neurons the baseline IPSC amplitudes from mice treated with ketamine are significantly weaker than those in control mice. Acute bath application of neuregulin-1 (NRG1) to cortical slices increases these IPSC amplitudes in mice treated with ketamine but not in controls. In PV+ interneurons, the baseline EPSC amplitudes from mice treated with ketamine are significantly weaker than those in control mice. Acute bath application of NRG1 to cortical slices increases these EPSC amplitudes in mice treated with ketamine but not in controls. We also found that mi...