Deficits in social behavior are found in neurodevelopmental disorders, including autism spectrum disorders (ASDs). Since abnormalities in cerebellar morphology and function are observed in ASD patients, the cerebellum is thought to play a role in social behavior. However, it remains unknown whether the cerebellum is involved in social behavior in other animals and how cerebellar circuits control social behavior. To address this issue, we employed zebrafish stereotyped orienting behavior as a model of social behaviors, in which a pair of adult zebrafish in two separate tanks approach each other, with one swimming at synchronized angles (orienting angles) with the other. We harnessed transgenic zebrafish that express botulinum toxin, which inhibits the release of neurotransmitters, in either granule cells or Purkinje cells (PCs), and zebrafish mutants of reelin , which is involved in the positioning of cerebellar neurons, including PCs. These zebrafish, deficient in the function or formation of cerebellar ne...

The Bone Morphogenetic Protein (BMP) signaling pathway is vital in neural progenitor cell proliferation, specification, and differentiation. The BMP signaling antagonist Gremlin 2 (Grem2) is the most potent natural inhibitor of BMP expressed in the adult brain; however its function remains unknown. To address this knowledge gap, we have analyzed mice lacking Grem2 via homologous recombination ( Grem2−/− ). Histological analysis of brain sections revealed significant scattering of CA3 pyramidal cells within the dentate hilus in the hippocampus of Grem2−/− mice. Furthermore, the number of proliferating neural stem cells and neuroblasts was significantly decreased in the subgranular zone of Grem2−/− mice compared with that of wild-type (WT) controls. Due to the role of hippocampal neurogenesis in neurological disorders, we tested mice on a battery of neurobehavioral tests. Grem2−/− mice exhibited increased anxiety on the elevated zero maze in response to acute and chronic stress. Specifically, male Grem2−/− m...

Animals, humans included, navigate their environments guided by sensory cues, responding adaptively to potential dangers and rewards. Avoidance behaviors serve as adaptive strategies in the face of signaled threats, but the neural mechanisms orchestrating these behaviors remain elusive. Current circuit models of avoidance behaviors indicate that the nucleus accumbens (NAc) in the ventral striatum plays a key role in signaled avoidance behaviors, but the nature of this engagement is unclear. Evolving perspectives propose the NAc as a pivotal hub for action selection, integrating cognitive and affective information to heighten the efficiency of both appetitive and aversive motivated behaviors. To unravel the engagement of the NAc during active and passive avoidance, we used calcium imaging fiber photometry to examine NAc GABAergic neuron activity in ad libitum moving mice performing avoidance behaviors. We then probed the functional significance of NAc neurons using optogenetics and genetically targeted or e...

Autonoetic consciousness (ANC), the ability to re-experience personal past events links episodic memory and self-consciousness by bridging awareness of oneself in a past event (i.e., during its encoding) with awareness of oneself in the present (i.e., during the reliving of a past event). Recent neuroscience research revealed a bodily form of self-consciousness, including the sense of agency (SoA) and the sense of body ownership (SoO) that are based on the integration of multisensory bodily inputs and motor signals. However, the relation between SoA and/or SoO with ANC is not known. Here, we used immersive virtual reality technology and motion tracking and investigated the potential association of SoA/SoO with ANC. For this, we exposed participants to different levels of visuomotor and perspectival congruency, known to modulate SoA and SoO, during the encoding of virtual scenes and collected ANC ratings 1 week after the encoding session. In a total of 74 healthy participants, we successfully induced system...

Tetrahydroxy stilbene glucoside (TSG) from Polygonum multiflorum exerts neuroprotective effects after ischemic stroke. We explored whether TSG improved ischemic stroke injury via PTEN-induced kinase 1 (PINK1)/Parkin-mediated mitophagy. Oxygen glucose deprivation/reoxygenation (OGD/R) in vitro model and middle cerebral artery occlusion (MCAO) rat model were established. Cerebral injury was assessed by neurological score, hematoxylin and eosin staining, 2,3,5-triphenyltetrazolium chloride staining, and brain water content. Apoptosis, cell viability, and mitochondrial membrane potential were assessed by flow cytometry, cell counting kit-8, and JC-1 staining, respectively. Colocalization of LC3-labeled autophagosomes with lysosome-associated membrane glycoprotein 2-labeled lysosomes or translocase of outer mitochondrial membrane 20-labeled mitochondria was observed with fluorescence microscopy. The ubiquitination level was determined using ubiquitination assay. The interaction between molecules was validated b...

Confirmation bias (CB) is a cognitive bias that allows us to fool ourselves by selectively filtering data and distorting analyses to support favored beliefs or hypotheses. In this article, I will briefly review some classic experiments from cognitive psychology that illustrate what a powerful, pernicious, and insidious force CB is. I will then discuss how to recognize CB in our own thinking and behavior and describe specific elements of good experimental design that can mitigate its effects. These elements—such as randomization and blinding—are conceptually straightforward but often difficult in practice and therefore not as widely implemented as they should be.

Obsessive–compulsive disorder (OCD) is a neuropsychiatric disorder characterized by obsessions and compulsions. Obsessions are intrusive thoughts or urges, and compulsions are repetitive behaviors that a person often performs to alleviate the anxiety related to these obsessions. The obsessions and compulsions associated with OCD can be debilitating, affecting the daily lives and overall quality of life for those with OCD (Pauls et al., 2014). OCD has a lifetime prevalence of ∼2–3% and although there are treatments for those diagnosed with OCD, unfortunately up to 50% of these patients continue to display symptoms (Dougherty et al., 2004). Better, more targeted treatment options are needed, and understanding the neurobiology of OCD is important in improving the treatment options for those affected by this disorder. Previous studies of OCD patients using neuroimaging techniques have identified increased activity of cortical and striatal regions (Pauls et al., 2014). Additionally, animal studies have also im...

In the article “Prolonged Activity Deprivation Causes Pre- and Postsynaptic Compensatory Plasticity at Neocortical Excitatory Synapses,” by Derek L. Wise, Yasmin Escobedo-Lozoya, Vera Valakh, Emma Y. Gao, Aishwarya Bhonsle, Qian L. Lei, Xinyu Cheng, Samuel B. Greene, Stephen D. Van Hooser, and Sacha B. Nelson, which was …

It remains unknown whether the Chinese tree shrew, regarded as the closest sister of primate, has evolved a dorsolateral prefrontal cortex (dlPFC) comparable with primates that is characterized by a fourth layer (L4) enriched with granular cells and reciprocal connections with the mediodorsal nucleus (MD). Here, we reported that following AAV-hSyn-EGFP expression in the MD neurons, the fluorescence micro-optical sectioning tomography revealed their projection trajectories and targeted brain areas, such as the hippocampus, the corpus striatum, and the dlPFC. Cre-dependent transsynaptic viral tracing identified the MD projection terminals that targeted the L4 of the dlPFC, in which the presence of granular cells was confirmed via cytoarchitectural studies by using the Nissl, Golgi, and vGlut2 stainings. Additionally, the L5/6 of the dlPFC projected back to the MD. These results suggest that the tree shrew has evolved a primate-like dlPFC which can serve as an alternative for studying cognition-related functi...

Animals have evolved innate responses to cues including social, food, and predator odors. In the natural environment, animals are faced with choices that involve balancing risk and reward where innate significance may be at odds with internal need. The ability to update the value of a cue through learning is essential for navigating changing and uncertain environments. However, the mechanisms involved in this modulation are not well defined in mammals. We have established a new olfactory assay that challenges a thirsty mouse to choose an aversive odor over an attractive odor in foraging for water, thus overriding their innate behavioral response to odor. Innately, mice prefer the attractive odor port over the aversive odor port. However, decreasing the probability of water at the attractive port leads mice to prefer the aversive port, reflecting a learned override of the innate response to the odors. The orbitofrontal cortex (OFC) is a fourth-order olfactory brain area, involved in flexible value associati...