The endogenous opioid system plays a crucial role in stress-induced analgesia. Mu-opioid receptors (MORs), one of the major opioid receptors, are expressed widely in subpopulations of cells throughout the CNS. However, the potential roles of MORs expressed in glutamatergic (MORGlut) and γ-aminobutyric acidergic (MORGABA) neurons in stress-induced analgesia remain unclear. By examining tail-flick latencies to noxious radiant heat of male mice, here we investigated the contributions of MORGABA and MORGlut to behavioral analgesia and activities of neurons projecting from periaqueductal gray (PAG) to rostral ventromedial medulla (RVM) induced by a range of time courses of forced swim exposure. The moderate but not transitory or prolonged swim exposure induced a MOR-dependent analgesia, although all of these three stresses enhanced β-endorphin release. Selective deletion of MORGABA but not MORGlut clearly attenuated analgesia and blocked the enhancement of activities of PAG-RVM neurons induced by moderate swim ...

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 ...

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...

In the article, “Perceptual Fading of a Stabilized Cortical Image: Replication in the Undergraduate Classroom,” by Nicole B. Massa, Jacob H. Deck, and Michael A. Grubb, which published …

The generation of surrogate data, i.e., the modification of data to destroy a certain feature, can be considered as the implementation of a null-hypothesis whenever an analytical approach is not feasible. Thus, surrogate data generation has been extensively used to assess the significance of spike correlations in parallel spike trains. In this context, one of the main challenges is to properly construct the desired null-hypothesis distribution and to avoid altering the single spike train statistics. A classical surrogate technique is uniform dithering (UD), which displaces spikes locally and uniformly distributed, to destroy temporal properties on a fine timescale while keeping them on a coarser one. Here, we compare UD against five similar surrogate techniques in the context of the detection of significant spatiotemporal spike patterns. We evaluate the surrogates for their performance, first on spike trains based on point process models with constant firing rate, and second on modeled nonstationary artifi...

The migration of neurons from their birthplace to their correct destination is one of the most crucial steps in brain development. Incomplete or incorrect migration yields ectopic neurons, which cause neurologic deficits or are negligible at best. However, the granule cells (GCs) in the cerebellar cortex may challenge this traditional view of ectopic neurons. When animals are born, GCs proliferate near the pia mater and then migrate down to the GC layer located deep in the cerebellar cortex. However, some GC-like cells stay in the molecular layer, a layer between the pia mater and GC layer, even in normal adult animals. These cells were named ectopic GCs nearly 50 years ago, but their abundance and functional properties remain unclear. Here, we have examined GCs in the molecular layer (mGCs) with a specific marker for mature GCs and transgenic mice in which GCs are sparsely labeled with a fluorescent protein. Contrary to the previous assumption that mGCs are a minor neuronal population, we have found that ...

Actions have consequences. Motor learning involves correcting actions that lead to movement errors and remembering these actions for future behavior. In most laboratory situations, movement errors have no physical consequences and simply indicate the progress of learning. Here, we asked how experiencing a physical consequence when making a movement error affects motor learning. Two groups of participants adapted to a new, prism-induced mapping between visual input and motor output while performing a precision walking task. Importantly, one group experienced an unexpected slip perturbation when making foot-placement errors during adaptation. Because of our innate drive for safety, and the fact that balance is fundamental to movement, we hypothesized that this experience would enhance motor memory. Learning generalized to different walking tasks to a greater extent in the group who experienced the adverse physical consequence. This group also showed faster relearning one week later despite exposure to a comp...

Mutations of SCN1A , which encodes the voltage-gated sodium channel Nav1.1, can cause epilepsy disorders such as Dravet syndrome (DS) that are comorbid with wide-ranging neurologic dysfunction. Many studies suggest that Nav1.1 haploinsufficiency causes forebrain GABAergic interneuron hypoexcitability, while pyramidal neuron physiology is mostly unaltered, and that this serves as a primary cell physiology phenotype linking mutation to disease. We hypothesized that deficits in inhibition would alter synaptic integration during activation of the hippocampal microcircuit, thus disrupting cellular information processing and leading to seizures and cognitive deficits. We tested this hypothesis using ex vivo whole-cell recordings from CA1 pyramidal neurons in a heterozygous Scn1a knock-out mouse model and wild-type (WT) littermates, measuring responses to single and patterned synaptic stimulation and spontaneous synaptic activity. Overall, our experiments reveal a surprising normalcy of excitatory and inhibitory ...

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 ...

Among the modulatory functions of thyrotropin-releasing hormone (TRH), an anorectic behavior in rodents is observed when centrally injected. Hypothalamic paraventricular nucleus (PVN) neurons receive serotonergic inputs from dorsal raphe nucleus and express serotonin (5HT) receptors such as 5HT1A, 5HT2A/2C, 5HT6, which are involved in 5HT-induced feeding regulation. Rats subjected to dehydration-induced anorexia (DIA) model show increased PVN TRH mRNA expression, associated with their decreased food intake. We analyzed whether 5HT input is implicated in the enhanced PVN TRH transcription that anorectic rats exhibit, given that 5HT increases TRH expression and release when studied in vitro . By using mHypoA-2/30 hypothalamic cell cultures, we found that 5HT stimulated TRH mRNA, pCREB, and pERK1/2 levels. By inhibiting basal PKA or PKC activities or those induced by 5HT, pCREB or pERK1/2 content did not increase suggesting involvement of both kinases in their phosphorylation. 5HT effect on TRH mRNA was not a...