Bombesin receptor subtype-3 (BRS3) is an orphan receptor that regulates energy homeostasis. We compared Brs3 driver mice with constitutive or inducible Cre recombinase activity. The constitutive BRS3-Cre mice show a reporter signal (Cre-dependent tdTomato) in the adult brain because of lineage tracing in the dentate gyrus, striatal patches, and indusium griseum, in addition to sites previously identified in the inducible BRS3-Cre mice (including hypothalamic and amygdala subregions, and parabrachial nucleus). We detected Brs3 reporter expression in the dentate gyrus at day 23 but not at postnatal day 1 or 5 months of age. Hypothalamic sites expressed reporter at all three time points, and striatal patches expressed Brs3 reporter at 1 day but not 5 months. Parabrachial nucleus Brs3 neurons project to the preoptic area, hypothalamus, amygdala, and thalamus. Both Cre recombinase insertions reduced Brs3 mRNA levels and BRS3 function, causing obesity phenotypes of different severity. These results demonstrate t...

The adaptable transcriptional response to changes in food availability not only ensures animal survival, but also lets progressing with embryonic development. Interestingly, the central nervous system is preferentially protected to periods of malnutrition, a phenomenon known as ‘ brain sparing ’. However, the mechanisms that mediates this response remains poorly understood. To get a better understanding of this, we used Drosophila melanogaster as a model, analysing the transcriptional response of neural stem cells (neuroblasts) and glia of the blood-brain barrier (BBB), from larvae of both sexes, during nutrient restriction using targeted DamID. We found differentially expressed genes in both neuroblasts and glia of the BBB, although the effect of nutrient deficiency was primarily observed in the BBB. We characterised the function of a nutritional sensitive gene expressed in the BBB, the serine protease homologue, scarface ( scaf ). Scaf is expressed in subperineurial glia in the BBB in response to nutriti...

Textbook descriptions of primary sensory cortex (PSC) revolve around single neurons’ representation of low-dimensional sensory features, such as visual object orientation in V1, location of somatic touch in S1, and sound frequency in A1. Typically, studies of PSC measure neurons’ responses along few (1 or 2) stimulus and/or behavioral dimensions. However, real-world stimuli usually vary along many feature dimensions and behavioral demands change constantly. In order to illuminate how A1 supports flexible perception in rich acoustic environments, we recorded from A1 neurons while rhesus macaques (one male, one female) performed a feature-selective attention task. We presented sounds that varied along spectral and temporal feature dimensions (carrier bandwidth and temporal envelope, respectively). Within a block, subjects attended to one feature of the sound in a selective change detection task. We found that single neurons tend to be high-dimensional, in that they exhibit substantial mixed selectivity for b...

The orbitofrontal cortex (OFC) and hippocampus share striking cognitive and functional similarities. As a result, both structures have been proposed to encode “cognitive maps” that provide useful scaffolds for planning complex behaviors. However while this function has been exemplified by spatial coding in neurons of hippocampal regions—particularly place and grid cells—spatial representations in the OFC have been investigated far less. Here we sought to address this by recording OFC neurons from male rats engaged in an open-field foraging task like that originally developed to characterize place fields in rodent hippocampal neurons. Single unit activity was recorded as rats searched for food pellets scattered randomly throughout a large enclosure. In some sessions, particular flavors of food occurred more frequently in particular parts of the enclosure; in others, only a single flavor was used. OFC neurons showed spatially-localized firing fields in both conditions, and representations changed between fla...

Human listeners achieve quick and effortless speech comprehension through computations of conditional probability using Bayes rule. However, the neural implementation of Bayesian perceptual inference remains unclear. Competitive-selection accounts (e.g. TRACE) propose that word recognition is achieved through direct inhibitory connections between units representing candidate words that share segments (e.g. hygiene and hijack share/haidʒ/). Manipulations that increase lexical uncertainty should increase neural responses associated with word recognition when words cannot be uniquely identified. In contrast, predictive-selection accounts (e.g. Predictive-Coding) proposes that spoken word recognition involves comparing heard and predicted speech sounds and using prediction error to update lexical representations. Increased lexical uncertainty in words like hygiene and hijack will increase prediction error and hence neural activity only at later time points when different segments are predicted. We collected ME...

Sonic Hedgehog (Shh) signaling from the primary cilium drives cerebellar granule cell precursor (GCP) proliferation. Mutations of hedgehog (Hh) pathway repressors commonly cause medulloblastoma, the most prevalent and malignant childhood brain tumor that arises from aberrant GCP proliferation. We demonstrate that Nestin Cre-driven conditional knockout of a Shh pathway repressor- Rab23 in the mouse brain of both genders caused mis-patterning of cerebellar folia and elevated GCP proliferation during early development, but with no prevalent occurrence of medulloblastoma at adult stage. Strikingly, Rab23- depleted GCPs exhibited up-regulated basal level of Shh pathway activities despite showing an abnormal ciliogenesis of primary cilia. In line with the compromised ciliation, Rab23- depleted GCPs were desensitized against Hh pathway activity stimulations by Shh ligand and Smoothened (Smo) agonist-SAG, and exhibited attenuated stimulation of Smo-localization on the primary cilium in response to SAG. These resul...

Sevoflurane is widely used in general anesthesia, especially for children. However, prolonged exposure to sevoflurane is reported to be associated with adverse effects on the development of brain in infant monkey. Neural stem cells (NSCs), with potent proliferation, differentiation, and renewing ability, provide an encouraging tool for basic research and clinical therapies for neurodegenerative diseases. We aim to explore the functional effects of injecting NSCs with phosphodiesterase 7A (PDE7A) knock-down in infant mice exposed to sevoflurane. The effects of PDE7A in NSCs proliferation and differentiation were determined by cell counting kit-8 (CCK-8) assay and differentiation-related gene expression assay, respectively. The effects of NSCs with modified PDE7A on mice’s long-term memory and learning ability were assessed by behavioral assays. Our data demonstrated that depleting PDE7A promoted, whereas forcing PDE7A suppressed the activation of cAMP/cAMP-response element binding protein (CREB) signaling a...

New information is rarely learned in isolation; instead, most of what we experience can be incorporated into or uses previous knowledge networks in some form. Previous knowledge in form of a cognitive map can facilitate knowledge acquisition and will influence how we learn new spatial information. Here, we developed a new spatial navigation task where food locations are learned in a large, gangway maze to test how mice learn a large spatial map over a longer time period—the HexMaze. Analyzing performance across sessions as well as on specific trials, we can show simple memory effects as well as multiple effects of previous knowledge of the map accelerating both online learning and performance increases over offline periods when incorporating new information. We could identify the following three main phases: (1) learning the initial goal location; (2) faster learning after 2 weeks when learning a new goal location; and then (3) the ability to express one-session learning, leading to long-term memory effect...

Learning in sensorimotor adaptation tasks has been viewed as an implicit learning phenomenon. The implicit process affords recalibration of existing motor skills so that the system can adjust to changes in the body or environment without relearning from scratch. However, recent findings suggest that the implicit process is heavily constrained, calling into question its utility in motor learning and the theoretical framework of sensorimotor adaptation paradigms. These inferences have been based mainly on results from single bouts of training, where explicit compensation strategies, such as explicitly re-aiming the intended movement direction, contribute a significant proportion of adaptive learning. It is possible, however, that the implicit process supersedes explicit compensation strategies over repeated practice sessions. We tested this by dissociating the contributions of explicit re-aiming strategies and the implicit process in human participants over five consecutive days of training. Despite a substa...

The term “memory strength” generally refers to how well one remembers something. But more precisely it contains multiple modalities, such as how easily, how accurately, how confidently and how vividly we remember it. In human, these modalities of memory strength are dissociable. In this study, we asked whether we can isolate a behavioral component that is dissociable from others in hippocampus-dependent memory tasks in mice, which potentially reflect a modality of memory strength. Using a virus-mediated inducible method, we ablated immature neurons in the dentate gyrus in mice after we trained the mice with hippocampus-dependent memory tasks normally. In memory retrieval tests, these ablated mice initially showed intact performance. However, the ablated mice ceased learned behavior prematurely within a trial compared with control mice. In addition, the ablated mice showed shorter duration of individual episodes of learned behavior. Both affected behavioral measurements point to persistence of learned behav...