Large interindividual variability in the effects of low-intensity transcranial electrical stimulation (tES) considerably limits its potential for clinical applications. It has been recently proposed that individualizing stimulation dose by accounting for interindividual anatomic differences would reduce the variability in electric fields (E-fields) over the targeted cortical site and therefore produce more consistent behavioral outcomes. However, improvement in behavioral outcomes following individualized dose tES has never been compared with that of conventional fixed dose tES. In this study, we aimed to empirically evaluate the effect of individualized dose tES on behavior and further compare it with the effects of sham and fixed dose stimulations. We conducted a single-blinded, sham-controlled, repeated-measures study to examine the impact of transcranial direct current stimulation on motor learning and that of transcranial alternating current stimulation on the working memory of 42 healthy adult indivi...

The introduction of Internet-connected technologies to the classroom has the potential to revolutionize STEM education by allowing students to perform experiments in complex models that are unattainable in traditional teaching laboratories. By connecting laboratory equipment to the cloud, we introduce students to experimentation in pluripotent stem cell (PSC)-derived cortical organoids in two different settings: using microscopy to monitor organoid growth in an introductory tissue culture course and using high-density (HD) multielectrode arrays (MEAs) to perform neuronal stimulation and recording in an advanced neuroscience mathematics course. We demonstrate that this approach develops interest in stem cell and neuroscience in the students of both courses. All together, we propose cloud technologies as an effective and scalable approach for complex project-based university training.

Serotonergic neurons in the rostral ventral medulla (RVM) contribute to bidirectional control of pain through modulation of spinal and trigeminal nociceptive networks. Deficits in this pathway are believed to contribute to pathologic pain states, but whether changes in serotonergic mechanisms are pro- or antinociceptive is debated. We used a combination of optogenetics and fiber photometry to examine these mechanisms more closely. We find that optogenetic activation of RVM serotonergic afferents in the spinal cord of naive mice produces mechanical hypersensitivity and conditioned place aversion (CPA). Neuropathic pain, produced by chronic constriction injury of the infraorbital nerve (CCI-ION), evoked a tonic increase in serotonin (5HT) concentrations within the spinal trigeminal nucleus caudalis (SpVc), measured with liquid chromatography-tandem mass spectroscopy (LC-MS/MS). By contract, CCI-ION had no effect on the phasic serotonin transients in SpVc, evoked by noxious pinch, and measured with fiber phot...

Magnetoencephalography based on superconducting quantum interference devices (SQUIDs) has been shown to improve the diagnosis and surgical treatment decision for presurgical evaluation of drug-resistant epilepsy. Still, its use remains limited because of several constraints such as cost, fixed helmet size, and the obligation of immobility. A new generation of sensors, optically pumped magnetometers (OPMs), could overcome these limitations. In this study, we validate the ability of helium-based OPM (4He-OPM) sensors to record epileptic brain activity thanks to simultaneous recordings with intracerebral EEG [stereotactic EEG (SEEG)]. We recorded simultaneous SQUIDs-SEEG and 4He-OPM-SEEG signals in one patient during two sessions. We show that epileptic activities on intracerebral EEG can be recorded by OPMs with a better signal-to noise ratio than classical SQUIDs. The OPM sensors open new venues for the widespread application of magnetoencephalography in the management of epilepsy and other neurologic disea...

Working memory is an executive function that orchestrates the use of limited amounts of information, referred to as working memory capacity, in cognitive functions. Cannabis exposure impairs working memory in humans; however, it is unclear whether Cannabis facilitates or impairs rodent working memory and working memory capacity. The conflicting literature in rodent models may be at least partly because of the use of drug exposure paradigms that do not closely mirror patterns of human Cannabis use. Here, we used an incidental memory capacity paradigm where a novelty preference is assessed after a short delay in spontaneous recognition-based tests. Either object or odor-based stimuli were used in test variations with sets of identical [identical stimuli test (IST)] and different [different stimuli test (DST)] stimuli (three or six) for low-memory and high-memory loads, respectively. Additionally, we developed a human-machine hybrid behavioral quantification approach which supplements stopwatch-based scoring ...

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...

We present a cost-effective, compact foot-print, and open-source Raspberry Pi-based widefield imaging system. The compact nature allows the system to be used for close-proximity dual-brain cortical mesoscale functional-imaging to simultaneously observe activity in two head-fixed animals in a staged social touch-like interaction. We provide all schematics, code, and protocols for a rail system where head-fixed mice are brought together to a distance where the macrovibrissae of each mouse make contact. Cortical neuronal functional signals (GCaMP6s; genetically encoded Ca2+ sensor) were recorded from both mice simultaneously before, during, and after the social contact period. When the mice were together, we observed bouts of mutual whisking and cross-mouse correlated cortical activity across the cortex. Correlations were not observed in trial-shuffled mouse pairs, suggesting that correlated activity was specific to individual interactions. Whisking-related cortical signals were observed during the period whe...

Kirrel3 is a cell-adhesion molecule that instructs the formation of specific synapses during brain development in mouse and Kirrel3 variants may be risk factors for autism and intellectual disabilities in humans. Kirrel3 is predicted to undergo alternative splicing but brain isoforms have not been studied. Here, we present the first in-depth characterization of Kirrel3 isoform diversity in brain using targeted, long-read mRNA sequencing of mouse hippocampus. We identified 19 isoforms with predicted transmembrane and secreted forms and show that even rare isoforms generate detectable protein in the brain. We also analyzed publicly-available long-read mRNA databases from human brain tissue and found 11 Kirrel3 isoforms that, similar to mouse, encode transmembrane and secreted forms. In mice and humans, Kirrel3 diversity arises from alternative, independent use of protein-domain coding exons and alternative early translation-stop signals. Intriguingly, the alternatively spliced exons appear at branch points i...