Neuroscience Research最新文献

Duplication of chromosome 15q11-13 has been reported to be one of the most frequent cytogenetic copy number variations in autism spectrum disorder (ASD), and a mouse model of paternal 15q11-13 duplication was generated, termed 15q dup mice. While previous studies have replicated some of the behavioral and brain structural phenotypes of ASD separately, the relationship between brain structure and behavior has rarely been examined. In this study, we performed behavioral experiments related to anxiety and social behaviors and magnetic resonance imaging (MRI) using the same set of 15q dup and wild-type mice. 15q dup mice showed increased anxiety and a tendency toward alterations in social behaviors, as reported previously, as well as variability in terms of sociability. MRI analysis revealed that a lower sociability index was correlated with a smaller gray matter volume in the right medial entorhinal cortex. These results may help to understand how variability in behavioral phenotypes of ASD arises even in individuals with the same genetic background and to determine the individual differences in neurodevelopmental trajectory correlated with specific brain structures that underlie these phenotypes.

Processing emotionally meaningful stimuli and eliciting appropriate valence-specific behavior in response is a critical brain function for survival. Thus, how positive and negative valence are represented in neural circuits and how corresponding neural substrates interact to cooperatively select appropriate behavioral output are fundamental questions. In previous work, we identified that two amygdala intercalated clusters show opposite response selectivity to fear- and anxiety-inducing stimuli - negative valence (Hagihara et al., 2021). Here, we further show that the two clusters also exhibit distinctly different representations of stimuli with positive valence, demonstrating a broader role of the amygdala intercalated system beyond fear and anxiety. Together with the mutually inhibitory connectivity between the two clusters, our findings suggest that they serve as an ideal neural substrate for the integrated processing of valence for the selection of behavioral output.

The precuneus is an association area in the posteromedial cortex (PMC) that is involved in high-order cognitive functions through integrating multi-modal information. Previous studies have shown that the precuneus is functionally heterogeneous and subdivided into several subfields organized by the anterior-posterior and ventral-dorsal axes. Further, the precuneus forms the structural core of brain connectivity as a rich-club hub and overlaps with the default mode network (DMN) as the functional core. This review summarizes recent research on the connectivity and cognitive functions of the precuneus. We then present our recent tractography-based studies of the precuneus and contextual these results here with respect to possible cognitive functions and resting-state networks.

Environmental factors have well-documented impacts on brain development and mental health. Therefore, it is crucial to employ a reliable assay system to assess the spatial preference of model animals. In this study, we introduced an unbiased quadrant chamber assay system and discovered that parental pup-gathering behavior takes place in a very efficient manner. Furthermore, we found that test mice exhibited preferences for specific environments in both spontaneous and parental pup-gathering behavior contexts. Notably, the spatial preferences of autism spectrum disorder model animals were initially suppressed but later equalized during the spontaneous behavior assay, accompanied by increased time spent in the preferred chamber. In conclusion, our novel quadrant chamber assay system provides an ideal platform for investigating the spatial preference of mice, offering potential applications in studying environmental impacts and exploring neurodevelopmental and psychiatric disorder models.

Large-scale brain networks undergo functional reorganization over the course of the lifespan, with concurrent implications for cognition. Characterizing network connectivity during a task may provide complementary insight into cognitive development and aging, to that provided by resting-state. We assessed network background connectivity, which refers to connectivity that remains after task effects have been regressed out, during a visual memory-encoding task in a lifespan sample. More specifically we assessed the within- and between-network background connectivity of the default mode, salience, and frontoparietal networks. Within-network background connectivity of salience and frontoparietal networks differed between age groups, with late-life adults showing lower connectivity. We did not find an effect of age group in default mode network background connectivity, contrary to previous findings using resting-state. However, default mode between-network background connectivity with salience and frontoparietal networks was greater in mid-life and late-life adults than in younger age groups. Overall, our findings in a lifespan sample are in line with previous observations of age-related network de-differentiation. However, the lack of age effect in default mode network background connectivity suggests that background connectivity indeed represents a complementary measure to resting-state connectivity, providing a differential glance of network connectivity during a particular state.

Lewy body diseases, including Parkinson's disease (PD), are characterized by the spread of alpha-synuclein (αSyn) between neurons across synapses, a process crucial for understanding their pathophysiology and developing effective treatments. In this study, we aimed to investigate the role of neuronal activity in releasing αSyn from human induced pluripotent stem cell-derived dopaminergic neurons. We examined human induced pluripotent stem cell-derived dopaminergic neurons, both healthy and those with the αSyn gene mutation associated with PD. We employed pharmacological agents and optogenetic techniques and demonstrated that increased neuronal activity, induced by bicuculline or optogenetic stimulation, significantly enhances αSyn release. However, suppression of neuronal activity with cyanquixaline reduces αSyn secretion. These findings underscore the pivotal role of neuronal activity in αSyn transmission between neurons, showing its potential impact on the spread of Lewy pathology in patients with neurodegenerative diseases like PD. Therefore, this study advances our understanding of PD and opens new avenues for therapeutic strategies to mitigate Lewy body disease progression.

Large-scale brain simulation allows us to understand the interaction of vast numbers of neurons having nonlinear dynamics to help understand the information processing mechanisms in the brain. The scale of brain simulations continues to rise as computer performance improves exponentially. However, a simulation of the human whole brain has not yet been achieved as of 2024 due to insufficient computational performance and brain measurement data. This paper examines technological trends in supercomputers, cell type classification, connectomics, and large-scale activity measurements relevant to whole-brain simulation. Based on these trends, we attempt to predict the feasible timeframe for mammalian whole-brain simulation. Our estimates suggest that mouse whole-brain simulation at the cellular level could be realized around 2034, marmoset around 2044, and human likely later than 2044.

Performance decrement under excessive psychological pressure is known as "choking," yet its mechanisms and neural foundations remain underexplored. Hypothesizing that changes in the internal model could induce choking, we conducted a 7 T functional MRI introducing excessive pressure through a rare Jackpot condition that offers high rewards for successful performance. Twenty-nine volunteers underwent a visual reaching task. We monitored practice and main sessions to map the task's internal model through learning. Participants were pre-informed of four potential reward conditions upon success at the beginning of the main session task. The success rates in the Jackpot condition were significantly lower than in other conditions, indicative of choking. During the preparation phase, activations in the cerebellum and the middle temporal visual area (hMT+) were associated with Jackpot-specific failures. The cluster in the cerebellar hemisphere overlapped with the internal model regions identified by a learning-related decrease in activation during the practice session. We observed task-specific functional connectivity between the cerebellum and hMT+. These findings suggest a lack of sensory attenuation when an internal model predicting the outcome of one's actions is preloaded during motor preparation. Within the active inference framework of motor control, choking stems from the cerebellum's internal model modulation by psychological pressure, manifested through improper sensory attenuation.

Temperature is a constant environmental factor on Earth, acting as a continuous stimulus that organisms must constantly perceive to survive. Organisms possess neural systems that receive various types of environmental information, including temperature, and mechanisms for adapting to their surroundings. This paper provides insights into the neural circuits and intertissue networks involved in physiological temperature responses, specifically the mechanisms of "cold tolerance" and "temperature acclimation," based on an analysis of the nematode Caenorhabditis elegans as an experimental system for neural and intertissue information processing.