Comorbid anxiety and depressive symptoms in chronic pain are a common health problem, but the underlying mechanisms remain unclear. Previously, we have demonstrated that sensitization of the CeA neurons via decreased GABAergic inhibition contributes to anxiety-like behaviors in neuropathic pain rats. In this study, by using male Sprague Dawley rats, we reported that the CeA plays a key role in processing both sensory and negative emotional-affective components of neuropathic pain. Bilateral electrolytic lesions of CeA, but not lateral/basolateral nucleus of the amygdala (LA/BLA), abrogated both pain hypersensitivity and aversive and depressive symptoms of neuropathic rats induced by spinal nerve ligation (SNL). Moreover, SNL rats showed structural and functional neuroplasticity manifested as reduced dendritic spines on the CeA neurons and enhanced LTD at the LA/BLA-CeA synapse. Disruption of GluA2-containing AMPAR trafficking and endocytosis from synapses using synthetic peptides, either pep2-EVKI or Tat-G...

The human brain continuously processes streams of visual input. Yet, a single image typically triggers neural responses that extend beyond 1s. To understand how the brain encodes and maintains successive images, we analyzed with electroencephalography the brain activity of human subjects while they watched ∼5000 visual stimuli presented in fast sequences. First, we confirm that each stimulus can be decoded from brain activity for ∼1s, and we demonstrate that the brain simultaneously represents multiple images at each time instant. Second, we source localize the corresponding brain responses in the expected visual hierarchy and show that distinct brain regions represent, at each time instant, different snapshots of past stimulations. Third, we propose a simple framework to further characterize the dynamical system of these traveling waves. Our results show that a chain of neural circuits, which each consist of (1) a hidden maintenance mechanism and (2) an observable update mechanism, accounts for the dynami...

Despina Antypa, Aurore A. Perrault, Patrik Vuilleumier, Sophie Schwartz, and Ulrike Rimmele (see pages [7259–7266][1]) Newly encoded memories are strengthened and stabilized for long-term retention through a process called consolidation. Consolidated memories are not immutable, however. Each

In the article “REST Protects Dopaminergic Neurons from Mitochondrial and α-Synuclein Oligomer Pathology in an Alpha Synuclein Overexpressing BAC-Transgenic Mouse Model,” by Brent J. Ryan, Nora Bengoa-Vergniory, Matthew Williamson, Ecem Kirkiz, Rosalind Roberts, Gabriele Corda, Maximilian Sloan

Lower urinary tract or voiding disorders are prevalent across all ages and affect >40% of adults over 40 years old, leading to decreased quality of life and high health care costs. The pontine micturition center (PMC; i.e., Barrington's nucleus) contains a large population of neurons that localize the stress-related neuropeptide, corticotropin-releasing hormone (CRH) and project to neurons in the spinal cord to regulate micturition. How the PMC and CRH-expressing neurons in the PMC control volitional micturition is of critical importance for human voiding disorders. To investigate the specific role of CRH in the PMC, neurons in the PMC-expressing CRH were optogenetically activated during in vivo cystometry in unanesthetized mice of either sex. Optogenetic activation of CRH-PMC neurons led to increased intermicturition interval and voided volume, similar to the altered voiding phenotype produced by social stress. Female mice showed a significantly more pronounced phenotype change compared with male mice. Th...

The effective development of novel therapies in mouse models of neurological disorders relies on behavioural assessments that provide accurate read-outs of neuronal dysfunction and/or degeneration. We designed an automated behavioural testing system (‘PiPaw’) which integrates an operant lever-pulling task directly into the mouse home-cage. This task is accessible to group-housed mice 24-hours per day, enabling high-throughput longitudinal analysis of forelimb motor learning. Moreover, this design eliminates the need for exposure to novel environments and minimizes experimenter interaction, significantly reducing two of the largest stressors associated with animal behaviour. Male mice improved their performance of this task over one week of testing by reducing inter-trial variability of reward-related kinematic parameters (pull amplitude or peak velocity). In addition, mice displayed short-term improvements in reward rate, and a concomitant decrease in movement variability, over the course of brief bouts of...

Rhythmic rest-activity cycles are controlled by an endogenous clock. In Drosophila , this clock resides in ∼150 neurons organized in clusters whose hierarchy changes in response to environmental conditions. The concerted activity of the circadian network is necessary for the adaptive responses to synchronizing environmental stimuli. Thus far work was devoted to unravel the logic of the coordination of different clusters focusing on neurotransmitters and neuropeptides. We further explored communication in the adult male brain through ligands belonging to the Bone Morphogenetic Protein (BMP) pathway. Herein we show that the Lateral Neurons ventral (LNvs) express the small morphogen DECAPENTAPLEGIC (DPP). DPP expression in the large LNvs triggered a period lengthening phenotype, while its downregulation caused reduced rhythmicity and affected anticipation at dawn and dusk, underscoring DPP per se conveys time-of-day relevant information. Surprisingly, its expression in the large LNvs impaired circadian remode...

How do we attend to relevant auditory information in complex naturalistic scenes? Much research has focused on detecting which information is attended, without regarding underlying top-down control mechanisms. Studies investigating attentional control generally manipulate and cue specific features in simple stimuli. However, in naturalistic scenes it is impossible to dissociate relevant from irrelevant information based on low-level features. Instead, the brain has to parse and select auditory objects of interest. The neural underpinnings of object-based auditory attention remain not well understood. Here we recorded MEG while 15 healthy human subjects (9 female) prepared for the repetition of an auditory object presented in one of two overlapping naturalistic auditory streams. The stream containing the repetition was prospectively cued with 70% validity. Crucially, this task could not be solved by attending low-level features, but only by processing the objects fully. We trained a linear classifier on the...

The post-injury regenerative capacity of neurons is known to be mediated by a complex interaction of intrinsic regenerative pathways and external cues. In Caenorhabditis elegans , the initiation of axon regeneration is regulated by the non-muscle myosin light chain (MLC-4) phosphorylation signaling pathway. In this study, we have identified svh-16 / cdk-14 , a mammalian CDK14 homolog, as a positive regulator of axon regeneration in motor neurons. We then isolated the CDK-14-binding protein MIG-5/Disheveled (Dsh) and found that EGL-20/Wnt and the MIG-1/Frizzled receptor (Fz) are required for efficient axon regeneration. Further, we demonstrate that CDK-14 activates EPHX-1, the C. elegans homolog of the mammalian ephexin Rho-type GTPase guanine nucleotide-exchange factor (GEF), in a kinase-independent manner. EPHX-1 functions as a GEF for the CDC-42 GTPase, inhibiting myosin phosphatase, which maintains MLC-4 phosphorylation. These results suggest that CDK14 activates the RhoGEF–CDC42–MLC phosphorylation axi...

The role of the motor cortex in perceptual and cognitive functions is highly controversial. Here, we investigated the hypothesis that the motor cortex can be instrumental for translating foreign language vocabulary. Human participants of both sexes were trained on foreign language (L2) words and their native language translations over four consecutive days. L2 words were accompanied by complementary gestures (sensorimotor enrichment) or pictures (sensory enrichment). Following training, participants translated the auditorily-presented L2 words that they had learned. During translation, repetitive transcranial magnetic stimulation (rTMS) was applied bilaterally to a site within the primary motor cortex (Brodmann Area 4) located in the vicinity of the arm functional compartment. Responses within the stimulated motor region have previously been found to correlate with behavioral benefits of sensorimotor-enriched L2 vocabulary learning. Compared to sham stimulation, effective perturbation by rTMS slowed down t...