Amyotrophic lateral sclerosis (ALS) is a rapidly progressive and fatal neurodegenerative disorder that affects upper and lower motor neurons; however, its pathomechanism has not been fully elucidated. Using a comprehensive phosphoproteomic approach, we have identified elevated phosphorylation of Collapsin response mediator protein 1 (Crmp1) at serine 522 in the lumbar spinal cord of ALS model mice overexpressing a human superoxide dismutase mutant (SOD1G93A). We investigated the effects of Crmp1 phosphorylation and depletion in SOD1G93A mice using Crmp1S522A (Ser522→Ala) knock-in ( Crmp1k i /ki ) mice in which the S522 phosphorylation site was abolished and Crmp1 knock-out ( Crmp1 −/−) mice, respectively. Crmp1ki / ki / SOD1G93A mice showed longer latency to fall in a rotarod test while Crmp1 −/−/ SOD1G93A mice showed shorter latency compared with SOD1G93A mice. Survival was prolonged in Crmp1ki / ki / SOD1G93A mice but not in Crmp1 −/−/ SOD1G93A mice. In agreement with these phenotypic findings, residual ...

Adaptation plays an important role in sensory systems as it dynamically modifies sensitivity to allow the detection of stimulus changes. The vomeronasal system controls many social behaviors in most mammals by detecting pheromones released by conspecifics. Stimuli activate a transduction cascade in vomeronasal neurons that leads to spiking activity. Whether and how these neurons adapt to stimuli is still debated and largely unknown. Here, we measured short-term adaptation performing current-clamp whole-cell recordings by using diluted urine as a stimulus, as it contains many pheromones. We measured spike frequency adaptation in response to repeated identical stimuli of 2–10 s duration that was dependent on the time interval between stimuli. Responses to paired current steps, bypassing the signal transduction cascade, also showed spike frequency adaptation. We found that voltage-gated Na+ channels in VSNs undergo slow inactivation processes. Furthermore, recovery from slow inactivation of voltage-gated Na+ ...

Food choice is one of the most fundamental and most frequent value-based decisions for all animals including humans. However, the neural circuitry involved in food-based decisions is only recently being addressed. Given the relatively fast dynamics of decision formation, electroencephalography (EEG)-informed fMRI analysis is highly beneficial for localizing this circuitry in humans. Here, by using the EEG correlates of evidence accumulation in a simultaneously recorded EEG-fMRI dataset, we found a significant role for the right temporal-parietal operculum (PO) and medial insula including gustatory cortex (GC) in binary choice between food items. These activations were uncovered by using the “EEG energy” (power 2 of EEG) as the BOLD regressor and were missed if conventional analysis with the EEG signal itself were to be used, in agreement with theoretical predictions for EEG and BOLD relations. No significant positive correlations were found with higher powers of EEG (powers 3 or 4) pointing to specificity ...

As Huntington’s disease (HD) progresses, there is a significant loss of neurons in the striatum in addition to a distinct thinning of the cerebral cortex. Despite an early presence of sensorimotor deficits in patients with HD, electrophysiological studies designed to assess the integrity of thalamocortical circuits are sparse. Using the R6/2 mouse model of HD, we provide evidence of reduced connectivity between thalamic cells and their targeted cortical regions. Whole-cell patch clamp recordings from ventral anterolateral nucleus (VAL; motor) and ventral posteromedial nucleus (VPM; somatosensory) thalamic neurons in ex vivo brain slices of R6/2 and wild-type (WT) mice revealed that cells in both thalamic nuclei of R6/2 mice exhibited significant differences in passive and active cell membrane properties (smaller cell membrane capacitances, faster decay time constants and increased input resistances) compared with WT cells. Although only cells in the VPM of symptomatic R6/2 mice had more depolarized resting...

Although visual object recognition is well studied and relatively well understood, much less is known about how shapes are recognized by touch and how such haptic stimuli might be compared with visual shapes. One might expect that the processes of visual and haptic object recognition engage similar brain structures given the advantages of avoiding redundant brain circuitry and indeed there is some evidence that this is the case. A potentially fruitful approach to understanding the differences in how shapes might be neurally represented is to find an algorithmic method of comparing shapes, which agrees with human behavior and determines whether that method differs between different modality conditions. If not, it would provide further evidence for a shared representation of shape. We recruited human participants to perform a one-back same–different visual and haptic shape comparison task both within (i.e., comparing two visual shapes or two haptic shapes) and across (i.e., comparing visual with haptic shape...

Women report greater cigarette cravings during the menstrual cycle phase with higher circulating levels of 17β-estradiol (E2), which is metabolized to estrone (E1). Both E2 and E1 bind to estrogen receptors (ERs), which have been highly studied in the breast, uterus, and ovary. Recent studies have found that ERs are also located on GABAergic medium spiny neurons (MSNs) within the nucleus accumbens core (NAcore). Glutamatergic plasticity in NAcore MSNs is altered following nicotine use; however, it is unknown whether estrogens impact this neurobiological consequence. To test the effect of estrogen on nicotine use, we ovariectomized (OVX) female rats that then underwent nicotine self-administration acquisition and compared them to ovary-intact (sham) rats. The OVX animals then received either sesame oil (vehicle), E2, or E1+E2 supplementation for 4 or 20 d before nicotine sessions. While both ovary-intact and OVX females readily discriminated levers, OVX females consumed less nicotine than sham females. Furt...

Human multisensory grasping movements (i.e., seeing and feeling a handheld object while grasping it with the contralateral hand) are superior to movements guided by each separate modality. This multisensory advantage might be driven by the integration of vision with either the haptic position only or with both position and size cues. To contrast these two hypotheses, we manipulated visual uncertainty (central vs peripheral vision) and the availability of haptic cues during multisensory grasping. We showed a multisensory benefit regardless of the degree of visual uncertainty suggesting that the integration process involved in multisensory grasping can be flexibly modulated by the contribution of each modality. Increasing visual uncertainty revealed the role of the distinct haptic cues. The haptic position cue was sufficient to promote multisensory benefits evidenced by faster actions with smaller grip apertures, whereas the haptic size was fundamental in fine-tuning the grip aperture scaling. These results ...

People with photosensitive epilepsy (PSE) are prone to seizures elicited by visual stimuli. The possibility of inducing epileptiform activity in a reliable way makes PSE a useful model to understand epilepsy, with potential applications for the development of new diagnostic methods and new treatments for epilepsy. A relationship has been demonstrated between PSE and both occipital and more widespread cortical hyperexcitability using various types of stimulation. Here we aimed to test whether hyperexcitability could be inferred from resting interictal electroencephalographic (EEG) data without stimulation. We considered a cohort of 46 individuals with idiopathic generalized epilepsy who underwent EEG during intermittent photic stimulation: 26 had a photoparoxysmal response (PPR), the PPR group, and 20 did not, the non-PPR group. For each individual, we computed functional networks from the resting EEG data before stimulation. We then placed a computer model of ictogenicity into the networks and simulated th...

Neuroscience is not just for neuroscientists. It is for everyone, but it is absent from our high schools. High schools have a huge investment in STEM but do not include neuroscience, although neuroscience is more interesting and relevant to a person’s daily life than most other sciences. However, neuroscience opportunities are increasing for teenagers outside the standard curriculum.

Neurosciences and digital technologies combine into the booming field of “neurotechnologies” (NT). Prospects for medical applications are very promising. If the GAFAM invest millions of dollars in NT, this is not only to develop brain-machine interfaces to overcome disabilities and mental pathologies. There are also commercial issues aimed at the public, via the exploitation of brain data for personal uses and for supervision of individual behaviors. The capacity of NT to “manipulate the brains” calls for vigilance in two particular areas: respect of mental autonomy and protection of brain data. A major issue is to assess whether existing laws on the protection of human rights are sufficient to protect mental privacy or whether new rights - NeuroRights- must be established specifically. The present era is characterized by major advances in neurosciences and in digital technologies. Both combine into a booming field of investigation called “neurotechnologies” (NTs) that result from research into brain path...