Ubiquitin-specific protease 2 (USP2) participates in glucose metabolism in peripheral tissues such as the liver and skeletal muscles. However, the glucoregulatory role of USP2 in the CNS is not well known. In this study, we focus on USP2 in the ventromedial hypothalamus (VMH), which has dominant control over systemic glucose homeostasis. ISH, using a Usp2 -specific probe, showed that Usp2 mRNA is present in VMH neurons, as well as other glucoregulatory nuclei, in the hypothalamus of male mice. Administration of a USP2-selective inhibitor ML364 (20 ng/head), into the VMH elicited a rapid increase in the circulating glucose level in male mice, suggesting USP2 has a suppressive role on glucose mobilization. ML364 treatment also increased serum norepinephrine concentration, whereas it negligibly affected serum levels of insulin and corticosterone. ML364 perturbated mitochondrial oxidative phosphorylation in neural SH-SY5Y cells and subsequently promoted the phosphorylation of AMP-activated protein kinase (AMPK...

The optic tectum (OT) is an avian midbrain structure involved in the integration of visual and auditory stimuli. Studies in the barn owl, an auditory specialist, have shown that spatial auditory information is topographically represented in the OT. Little is known about how auditory space is represented in the midbrain of birds with generalist hearing, i.e., most of avian species lacking peripheral adaptations such as facial ruffs or asymmetric ears. Thus, we conducted in vivo extracellular recordings of single neurons in the OT and in the external portion of the formatio reticularis lateralis (FRLx), a brain structure located between the inferior colliculus (IC) and the OT, in anaesthetized chickens of either sex. We found that most of the auditory spatial receptive fields (aSRFs) were spatially confined both in azimuth and elevation, divided into two main classes: round aSRFs, mainly present in the OT, and annular aSRFs, with a ring-like shape around the interaural axis, mainly present in the FRLx. Our d...

Making accurate decisions often involves the integration of current and past evidence. Here, we examine the neural correlates of conflict and evidence integration during sequential decision-making. Female and male human patients implanted with deep-brain stimulation (DBS) electrodes and age-matched and gender-matched healthy controls performed an expanded judgment task, in which they were free to choose how many cues to sample. Behaviorally, we found that while patients sampled numerically more cues, they were less able to integrate evidence and showed suboptimal performance. Using recordings of magnetoencephalography (MEG) and local field potentials (LFPs; in patients) in the subthalamic nucleus (STN), we found that β oscillations signaled conflict between cues within a sequence. Following cues that differed from previous cues, β power in the STN and cortex first decreased and then increased. Importantly, the conflict signal in the STN outlasted the cortical one, carrying over to the next cue in the seque...

Tohar S. Yarden, Adi Mizrahi, and Israel Nelken (see pages [4629–4651][1]) The nervous system has evolved to minimize processing of repetitive or otherwise uninformative stimuli to accentuate representations of novel or salient stimuli. Neural adaptation to common stimuli occurs at multiple

In the article “Site of Action of Brain Neurosteroid Pregnenolone Sulfate at the N-Methyl-D-Aspartate Receptor,” by Barbora Hrcka Krausova, Bohdan Kysilov, Jiri Cerny, Vojtech Vyklicky, Tereza Smejkalova, Marek Ladislav, Ales Balik, Miloslav Korinek, Hana Chodounska, Eva Kudova, and Ladislav

hMT+/V5 is a region in the middle occipitotemporal cortex that responds preferentially to visual motion in sighted people. In cases of early visual deprivation, hMT+/V5 enhances its response to moving sounds. Whether hMT+/V5 contains information about motion directions and whether the functional enhancement observed in the blind is motion specific, or also involves sound source location, remains unsolved. Moreover, the impact of this cross-modal reorganization of hMT+/V5 on the regions typically supporting auditory motion processing, like the human planum temporale (hPT), remains equivocal. We used a combined functional and diffusion-weighted MRI approach and individual in-ear recordings to study the impact of early blindness on the brain networks supporting spatial hearing in male and female humans. Whole-brain univariate analysis revealed that the anterior portion of hMT+/V5 responded to moving sounds in sighted and blind people, while the posterior portion was selective to moving sounds only in blind pa...

Speech is often degraded by environmental noise or hearing impairment. People can compensate for degradation, but this requires cognitive effort. Previous research has identified frontotemporal networks involved in effortful perception, but materials in these works were also less intelligible, and so it is not clear whether activity reflected effort or intelligibility differences. We used functional magnetic resonance imaging to assess the degree to which spoken sentences were processed under distraction and whether this depended on speech quality even when intelligibility of degraded speech was matched to that of clear speech (close to 100%). On each trial, male and female human participants either attended to a sentence or to a concurrent multiple object tracking (MOT) task that imposed parametric cognitive load. Activity in bilateral anterior insula reflected task demands; during the MOT task, activity increased as cognitive load increased, and during speech listening, activity increased as speech becam...

Although there is mounting evidence that input from the dorsal visual pathway is crucial for object processes in the ventral pathway, the specific functional contributions of dorsal cortex to these processes remain poorly understood. Here, we hypothesized that dorsal cortex computes the spatial relations among an object's parts, a process crucial for forming global shape percepts, and transmits this information to the ventral pathway to support object categorization. Using fMRI with human participants (females and males), we discovered regions in the intraparietal sulcus (IPS) that were selectively involved in computing object-centered part relations. These regions exhibited task-dependent functional and effective connectivity with ventral cortex, and were distinct from other dorsal regions, such as those representing allocentric relations, 3D shape, and tools. In a subsequent experiment, we found that the multivariate response of posterior (p)IPS, defined on the basis of part-relations, could be used to d...

Mutations in leucine-rich repeat kinase 2 (LRRK2) are the most common genetic cause of Parkinson's disease (PD), but the pathogenic mechanism underlying LRRK2 mutations remains unresolved. In this study, we investigate the consequence of inactivation of LRRK2 and its functional homolog LRRK1 in male and female mice up to 25 months of age using behavioral, neurochemical, neuropathological, and ultrastructural analyses. We report that LRRK1 and LRRK2 double knock-out ( LRRK DKO) mice exhibit impaired motor coordination at 12 months of age before the onset of dopaminergic neuron loss in the substantia nigra (SNpc). Moreover, LRRK DKO mice develop age-dependent, progressive loss of dopaminergic terminals in the striatum. Evoked dopamine (DA) release measured by fast-scan cyclic voltammetry in the dorsal striatum is also reduced in the absence of LRRK. Furthermore, LRRK DKO mice at 20–25 months of age show substantial loss of dopaminergic neurons in the SNpc. The surviving SNpc neurons in LRRK DKO mice at 25 mo...