查看更多>>摘要：Interval timing is involved in a variety of cog-nitive behaviors such as associative learning and decision-making.While it has been shown that time estimation is adaptive to the temporal context,it remains unclear how interval timing behavior is influenced by recent trial history.Here we found that,in mice trained to perform a licking-based interval timing task,a decrease of inter-reinforce-ment interval in the previous trial rapidly shifted the time of anticipatory licking earlier.Optogenetic inactivation of the anterior lateral motor cortex(ALM),but not the medial prefrontal cortex,for a short time before reward delivery caused a decrease in the peak time of anticipatory licking in the next trial.Electrophysiological recordings from the ALM showed that the response profiles preceded by short and long inter-reinforcement intervals exhibited task-engagement-dependent temporal scaling.Thus,interval timing is adap-tive to recent experience of the temporal interval,and ALM activity during time estimation reflects recent experience of interval.
查看更多>>摘要：Autapses selectively form in specific cell types in many brain regions.Previous studies have also found puta-tive autapses in principal spiny projection neurons(SPNs)in the striatum.However,it remains unclear whether these neurons indeed form physiologically functional autapses.We applied whole-cell recording in striatal slices and iden-tified autaptic cells by the occurrence of prolonged asyn-chronous release(AR)of neurotransmitters after bursts of high-frequency action potentials(APs).Surprisingly,we found no autaptic AR in SPNs,even in the presence of Sr2+.However,robust autaptic AR was recorded in parvalbumin(PV)-expressing neurons.The autaptic responses were medi-ated by GABAA receptors and their strength was dependent on AP frequency and number.Further computer simulations suggest that autapses regulate spiking activity in PV cells by providing self-inhibition and thus shape network oscilla-tions.Together,our results indicate that PV neurons,but not SPNs,form functional autapses,which may play important roles in striatal functions.
查看更多>>摘要：The parabrachial nucleus(PBN)integrates inter-oceptive and exteroceptive information to control various behavioral and physiological processes including breath-ing,emotion,and sleep/wake regulation through the neu-ral circuits that connect to the forebrain and the brainstem.However,the precise identity and function of distinct PBN subpopulations are still largely unknown.Here,we leveraged molecular characterization,retrograde tracing,optogenetics,chemogenetics,and electrocortical recording approaches to identify a small subpopulation of neurotensin-expressing neurons in the PBN that largely project to the emotional control regions in the forebrain,rather than the medulla.Their activation induces freezing and anxiety-like behaviors,which in turn result in tachypnea.In addition,optogenetic and chemogenetic manipulations of these neurons revealed their function in promoting wakefulness and maintaining sleep architecture.We propose that these neurons com-prise a PBN subpopulation with specific gene expression,connectivity,and function,which play essential roles in behavioral and physiological regulation.
查看更多>>摘要：Methcathinone(MCAT)belongs to the designer drugs called synthetic cathinones,which are abused world-wide for recreational purposes.It has strong stimulant effects,including enhanced euphoria,sensation,alertness,and empa-thy.However,little is known about how MCAT modulates neuronal activity in vivo.Here,we evaluated the effect of MCAT on neuronal activity with a series of functional approaches.C-Fos immunostaining showed that MCAT increased the number of activated neurons by 6-fold,espe-cially in sensory and motor cortices,striatum,and midbrain motor nuclei.In vivo single-unit recording and two-photon Ca2+imaging revealed that a large proportion of neurons increased spiking activity upon MCAT administration.Nota-bly,MCAT induced a strong de-correlation of population activity and increased trial-to-trial reliability,specifically during a natural movie stimulus.It improved the information-processing efficiency by enhancing the single-neuron cod-ing capacity,suggesting a cortical network mechanism of the enhanced perception produced by psychoactive stimulants.
查看更多>>摘要：Malfunction of the ventral subiculum(vSub),the main subregion controlling the output connections from the hippocampus,is associated with major depressive disorder(MDD).Although the vSub receives cholinergic innerva-tion from the medial septum and diagonal band of Broca(MSDB),whether and how the MSDB-to-vSub cholinergic circuit is involved in MDD is elusive.Here,we found that chronic unpredictable mild stress(CUMS)induced depres-sion-like behaviors with hyperactivation of vSub neurons,measured by c-fos staining and whole-cell patch-clamp recording.By retrograde and anterograde tracing,we con-firmed the dense MSDB cholinergic innervation of the vSub.In addition,transient restraint stress in CUMS increased the level of ACh in the vSub.Furthermore,chemogenetic stimulation of this MSDB-vSub innervation in ChAT-Cre mice induced hyperactivation of vSub pyramidal neurons along with depression-like behaviors;and local infusion of atropine,a muscarinic receptor antagonist,into the vSub attenuated the depression-like behaviors induced by chemo-genetic stimulation of this pathway and CUMS.Together,these findings suggest that activating the MSDB-vSub cho-linergic pathway induces hyperactivation of vSub pyrami-dal neurons and depression-like behaviors,revealing a novel circuit underlying vSub pyramidal neuronal hyperactivation and its associated depression.
查看更多>>摘要：The conventional approach to investigating functional connectivity in the block-designed study usually concatenates task blocks or employs residuals of task activa-tion.While providing many insights into brain functions,the block design adds more manipulation in functional network analysis that may reduce the purity of the blood oxygenation level-dependent signal.Recent studies utilized one single long run for task trials of the same condition,the so-called continuous design,to investigate functional connectivity based on task functional magnetic resonance imaging.Con-tinuous brain activities associated with the single-task condi-tion can be directly utilized for task-related functional con-nectivity assessment,which has been examined for working memory,sensory,motor,and semantic task experiments in previous research.But it remains unclear how the block and continuous design influence the assessment of task-related functional connectivity networks.This study aimed to dis-entangle the separable effects of block/continuous design and working memory load on task-related functional con-nectivity networks,by using repeated-measures analysis of variance.Across 50 young healthy adults,behavioral results of accuracy and reaction time showed a significant main effect of design as well as interaction between design and load.Imaging results revealed that the cingulo-opercular,fronto-parietal,and default model networks were associated with not only task activation,but significant main effects of design and load as well as their interaction on intra-and inter-network functional connectivity and global network topology.Moreover,a significant behavior-brain associa-tion was identified for the continuous design.This work has extended the evidence that continuous design can be used to study task-related functional connectivity and subtle brain-behavioral relationships.
查看更多>>摘要：To understand how the nervous system develops from a small pool of progenitors during early embryonic development,it is fundamentally important to identify the diversity of neuronal subtypes,decode the origin of neuronal diversity,and uncover the principles governing neuronal specification across different regions.Recent single-cell analyses have systematically identified neuronal diversity at unprecedented scale and speed,leaving the deconstruc-tion of spatiotemporal mechanisms for generating neuronal diversity an imperative and paramount challenge.In this review,we highlight three distinct strategies deployed by neural progenitors to produce diverse neuronal subtypes,including predetermined,stochastic,and cascade diversify-ing models,and elaborate how these strategies are imple-mented in distinct regions such as the neocortex,spinal cord,retina,and hypothalamus.Importantly,the identity of neural progenitors is defined by their spatial position and temporal patterning factors,and each type of progenitor cell gives rise to distinguishable cohorts of neuronal sub-types.Microenvironmental cues,spontaneous activity,and connectional pattern further reshape and diversify the fate of unspecialized neurons in particular regions.The illumination of how neuronal diversity is generated will pave the way for producing specific brain organoids to model human disease and desired neuronal subtypes for cell therapy,as well as understanding the organization of functional neural circuits and the evolution of the nervous system.
查看更多>>摘要：Primary familial brain calcification(PFBC)is an inherited neurodegenerative disorder mainly characterized by progressive calcium deposition bilaterally in the brain,accompanied by various symptoms,such as dystonia,ataxia,parkinsonism,dementia,depression,headaches,and epi-lepsy.Currently,the etiology of PFBC is largely unknown,and no specific prevention or treatment is available.During the past 10 years,six causative genes(SLC20A2,PDGFRB,PDGFB,XPR1,MYORG,and JAM2)have been identified in PFBC.In this review,considering mechanistic studies of these genes at the cellular level and in animals,we sum-marize the pathogenesis and potential preventive and thera-peutic strategies for PFBC patients.Our systematic analysis suggests a classification for PFBC genetic etiology based on several characteristics,provides a summary of the known composition of brain calcification,and identifies some potential therapeutic targets for PFBC.
查看更多>>摘要：The Coronavirus Disease 2019(COVID-19)pandemic has had an adverse impact on the physical and mental health of the public worldwide.In addition to illness in patients with COVID-19,isolated people and the general population have experienced mental health problems due to social distancing policies,mandatory lockdown,and other psychosocial factors,and the prevalence of depression and anxiety significantly increased during the pandemic.The purpose of this review is to elucidate the epidemiology,contributing factors,and pathogenesis of depression and anxiety.during the pandemic.These findings indicate that physicians and psychiatrists should pay more attention to and identify those with a high risk for mental problems,such as females,younger people,unmarried people,and those with a low educational level.In addition,researchers should focus on identifying the neural and neuroimmune mecha-nisms involved in depression and anxiety,and assess the intestinal microbiome to identify effective biomarkers.We also provide an overview of various intervention methods,including pharmacological treatment,psychological therapy,and physiotherapy,to provide a reference for different popu-lations to guide the development of optimized intervention methods.
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