Neurobiological evidence in rodents indicates that threat extinction incorporates reward neurocircuitry. Consequently, incorporating reward associations with an extinction memory may be an effective strategy to persistently attenuate threat responses. Moreover, while there is considerable research on the short-term effects of extinction strategies in humans, the long-term effects of extinction are rarely considered. In a within-subjects fMRI study with both female and male participants, we compared counterconditioning (a form of rewarded-extinction) to standard extinction at recent (24 hours) and remote (∼1 month) retrieval tests. Relative to standard extinction, rewarded extinction diminished 24-hour relapse of arousal and threat expectancy, and reduced activity in brain regions associated with the appraisal and expression of threat (e.g., thalamus, insula, periaqueductal gray). The retrieval of reward-associated extinction memory was accompanied by functional connectivity between the amygdala and the ven...

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...

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

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

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...

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...

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...

Physical exercise improves motor performance in individuals with Parkinson's disease and elevates mood in those with depression. Although underlying factors have not been identified, clues arise from previous studies showing a link between cognitive benefits of exercise and increases in brain-derived neurotrophic factor (BDNF). Here, we investigated the influence of voluntary wheel-running exercise on BDNF levels in the striatum of young male wild-type (WT) mice, and on the striatal release of a key motor-system transmitter, dopamine (DA). Mice were allowed unlimited access to a freely rotating wheel (runners) or a locked wheel (controls) for 30 d. Electrically evoked DA release was quantified in ex vivo corticostriatal slices from these animals using fast-scan cyclic voltammetry. We found that exercise increased BDNF levels in dorsal striatum (dStr) and increased DA release in dStr and in nucleus accumbens core and shell. Increased DA release was independent of striatal acetylcholine (ACh), and persisted ...