Within the prefrontal-cingulate cortex, abnormalities in coupling between neuronal networks can disturb the emotion-cognition interactions, contributing to the development of mental disorders such as depression. Despite this understanding, the neural circuit mechanisms underlying this phenomenon remain elusive. In this study, we present a biophysical computational model encompassing three crucial regions, including the dorsolateral prefrontal cortex, subgenual anterior cingulate cortex, and ventromedial prefrontal cortex. The objective is to investigate the role of coupling relationships within the prefrontal-cingulate cortex networks in balancing emotions and cognitive processes. The numerical results confirm that coupled weights play a crucial role in the balance of emotional cognitive networks. Furthermore, our model predicts the pathogenic mechanism of depression resulting from abnormalities in the subgenual cortex, and network functionality was restored through intervention in the dorsolateral prefrontal cortex. This study utilizes computational modeling techniques to provide an insight explanation for the diagnosis and treatment of depression.
Prefrontal Cortex/physiology* ; Humans ; Emotions/physiology* ; Cognition/physiology* ; Gyrus Cinguli/physiology* ; Computer Simulation ; Models, Neurological ; Neural Pathways/physiology* ; Nerve Net/physiology*

Autism Spectrum Disorders (ASDs) are reported as a group of neurodevelopmental disorders. The structural changes of brain regions including the hippocampus were widely reported in autistic patients and mouse models with dysfunction of ASD risk genes, but the underlying mechanisms are not fully understood. Here, we report that deletion of Trio, a high-susceptibility gene of ASDs, causes a postnatal dentate gyrus (DG) hypoplasia with a zigzagged suprapyramidal blade, and the Trio-deficient mice display autism-like behaviors. The impaired morphogenesis of DG is mainly caused by disturbing the postnatal distribution of postmitotic granule cells (GCs), which further results in a migration deficit of neural progenitors. Furthermore, we reveal that Trio plays different roles in various excitatory neural cells by spatial transcriptomic sequencing, especially the role of regulating the migration of postmitotic GCs. In summary, our findings provide evidence of cellular mechanisms that Trio is involved in postnatal DG morphogenesis.
Animals ; Dentate Gyrus/metabolism* ; Mice ; Morphogenesis/physiology* ; Neurons/pathology* ; Cell Movement ; Mice, Inbred C57BL ; Autism Spectrum Disorder/pathology* ; Mice, Knockout ; Neural Stem Cells ; Male ; Neurogenesis ; Autistic Disorder/genetics*

Human's robust cognitive abilities, including creativity and language, are made possible, at least in large part, by evolutionary changes made to the cerebral cortex. This paper reviews the biology and evolution of mammalian cortical radial glial cells (primary neural stem cells) and introduces the concept that a genetically step wise process, based on a core molecular pathway already in use, is the evolutionary process that has molded cortical neurogenesis. The core mechanism, which has been identified in our recent studies, is the extracellular signal-regulated kinase (ERK)-bone morphogenic protein 7 (BMP7)-GLI3 repressor form (GLI3R)-sonic hedgehog (SHH) positive feedback loop. Additionally, I propose that the molecular basis for cortical evolutionary dwarfism, exemplified by the lissencephalic mouse which originated from a larger gyrencephalic ancestor, is an increase in SHH signaling in radial glia, that antagonizes ERK-BMP7 signaling. Finally, I propose that: (1) SHH signaling is not a key regulator of primate cortical expansion and folding; (2) human cortical radial glial cells do not generate neocortical interneurons; (3) human-specific genes may not be essential for most cortical expansion. I hope this review assists colleagues in the field, guiding research to address gaps in our understanding of cortical development and evolution.
Humans ; Animals ; Biological Evolution ; Cerebral Cortex/metabolism* ; Neurogenesis/physiology* ; Signal Transduction/physiology* ; Hedgehog Proteins/metabolism* ; Ependymoglial Cells/physiology*

Neural activities differentiating bodies versus non-body stimuli have been identified in the occipitotemporal cortex of both humans and nonhuman primates. However, the neural mechanisms of coding the similarity of different individuals' bodies of the same species to support their categorical representations remain unclear. Using electroencephalography (EEG) and magnetoencephalography (MEG), we investigated the temporal and spatial characteristics of neural processes shared by different individual body silhouettes of the same species by quantifying the repetition suppression of neural responses to human and animal (chimpanzee, dog, and bird) body silhouettes showing different postures. Our EEG results revealed significant repetition suppression of the amplitudes of early frontal/central activity at 180-220 ms (P2) and late occipitoparietal activity at 220-320 ms (P270) in response to animal (but not human) body silhouettes of the same species. Our MEG results further localized the repetition suppression effect related to animal body silhouettes in the left supramarginal gyrus and left frontal cortex at 200-440 ms after stimulus onset. Our findings suggest two neural processes that are involved in spontaneous categorical representations of animal body silhouettes as a cognitive basis of human-animal interactions.
Humans ; Animals ; Male ; Electroencephalography ; Magnetoencephalography ; Female ; Young Adult ; Adult ; Pattern Recognition, Visual/physiology* ; Brain Mapping ; Photic Stimulation ; Brain/physiology* ; Dogs

Depressive disorder is a chronic, recurring, and potentially life-endangering neuropsychiatric disease. According to a report by the World Health Organization, the global population suffering from depression is experiencing a significant annual increase. Despite its prevalence and considerable impact on people, little is known about its pathogenesis. One major reason is the scarcity of reliable animal models due to the absence of consensus on the pathology and etiology of depression. Furthermore, the neural circuit mechanism of depression induced by various factors is particularly complex. Considering the variability in depressive behavior patterns and neurobiological mechanisms among different animal models of depression, a comparison between the neural circuits of depression induced by various factors is essential for its treatment. In this review, we mainly summarize the most widely used behavioral animal models and neural circuits under different triggers of depression, aiming to provide a theoretical basis for depression prevention.
Animals ; Disease Models, Animal ; Depressive Disorder/psychology* ; Humans ; Behavior, Animal/physiology* ; Nerve Net/physiopathology* ; Brain/physiopathology* ; Neural Pathways/physiopathology*

IL-33 and its receptor ST2 play crucial roles in tissue repair and homeostasis. However, their involvement in optic neuropathy due to trauma and glaucoma remains unclear. Here, we report that IL-33 and ST2 were highly expressed in the mouse optic nerve and retina. Deletion of IL-33 or ST2 exacerbated retinal ganglion cell (RGC) loss, retinal thinning, and nerve fiber degeneration following optic nerve (ON) injury. This heightened retinal neurodegeneration correlated with increased neurotoxic astrocytes in Il33^-/- mice. In vitro, rIL-33 mitigated the neurotoxic astrocyte phenotype and reduced the expression of pro-inflammatory factors, thereby alleviating the RGC death induced by neurotoxic astrocyte-conditioned medium in retinal explants. Exogenous IL-33 treatment improved RGC survival in Il33^-/- and WT mice after ON injury, but not in ST2^-/- mice. Our findings highlight the role of the IL-33/ST2 axis in modulating reactive astrocyte function and providing neuroprotection for RGCs following ON injury.
Animals ; Interleukin-33/genetics* ; Interleukin-1 Receptor-Like 1 Protein/genetics* ; Optic Nerve Injuries/pathology* ; Retinal Ganglion Cells/pathology* ; Astrocytes/pathology* ; Mice ; Mice, Knockout ; Mice, Inbred C57BL ; Neuroprotection/physiology*

Anxiety disorder is a major symptom of autism spectrum disorder (ASD) with a comorbidity rate of ~40%. However, the neural mechanisms of the emergence of anxiety in ASD remain unclear. In our study, we found that hyperactivity of basolateral amygdala (BLA) pyramidal neurons (PNs) in Shank3 InsG3680 knock-in (InsG3680^+/+) mice is involved in the development of anxiety. Electrophysiological results also showed increased excitatory input and decreased inhibitory input in BLA PNs. Chemogenetic inhibition of the excitability of PNs in the BLA rescued the anxiety phenotype of InsG3680^+/+ mice. Further study found that the diminished control of the BLA by medial prefrontal cortex (mPFC) and optogenetic activation of the mPFC-BLA pathway also had a rescue effect, which increased the feedforward inhibition of the BLA. Taken together, our results suggest that hyperactivity of the BLA and alteration of the mPFC-BLA circuitry are involved in anxiety in InsG3680^+/+ mice.
Animals ; Prefrontal Cortex/metabolism* ; Basolateral Nuclear Complex/metabolism* ; Mice ; Anxiety/metabolism* ; Nerve Tissue Proteins/genetics* ; Male ; Gene Knock-In Techniques ; Pyramidal Cells/physiology* ; Mice, Transgenic ; Neural Pathways/physiopathology* ; Mice, Inbred C57BL ; Microfilament Proteins

Rhythm, as a prominent characteristic of auditory experiences such as speech and music, is known to facilitate attention, yet its contribution to working memory (WM) remains unclear. Here, human participants temporarily retained a 12-tone sequence presented rhythmically or arrhythmically in WM and performed a pitch change-detection task. Behaviorally, while having comparable accuracy, rhythmic tone sequences showed a faster response time and lower response boundaries in decision-making. Electroencephalographic recordings revealed that rhythmic sequences elicited enhanced non-phase-locked beta-band (16 Hz-33 Hz) and theta-band (3 Hz-5 Hz) neural oscillations during sensory encoding and WM retention periods, respectively. Importantly, the two-stage neural signatures were correlated with each other and contributed to behavior. As beta-band and theta-band oscillations denote the engagement of motor systems and WM maintenance, respectively, our findings imply that rhythm facilitates auditory WM through intricate oscillation-based interactions between the motor and auditory systems that facilitate predictive attention to auditory sequences.
Humans ; Memory, Short-Term/physiology* ; Male ; Beta Rhythm/physiology* ; Female ; Theta Rhythm/physiology* ; Young Adult ; Auditory Perception/physiology* ; Adult ; Electroencephalography ; Acoustic Stimulation ; Reaction Time/physiology* ; Brain/physiology* ; Attention/physiology*

Persistent and maladaptive drug-related memories represent a key component in drug addiction. Converging evidence from both preclinical and clinical studies has demonstrated the potential efficacy of the memory reconsolidation updating procedure (MRUP), a non-pharmacological strategy intertwining two distinct memory processes: reconsolidation and extinction-alternatively termed "the memory retrieval-extinction procedure". This procedure presents a promising approach to attenuate, if not erase, entrenched drug memories and prevent relapse. The present review delineates the applications, molecular underpinnings, and operational boundaries of MRUP in the context of various forms of substance dependence. Furthermore, we critically examine the methodological limitations of MRUP, postulating potential refinement to optimize its therapeutic efficacy. In addition, we also look at the potential integration of MRUP and neurostimulation treatments in the domain of substance addiction. Overall, existing studies underscore the significant potential of MRUP, suggesting that interventions predicated on it could herald a promising avenue to enhance clinical outcomes in substance addiction therapy.
Humans ; Substance-Related Disorders/psychology* ; Memory Consolidation/physiology* ; Animals ; Extinction, Psychological/physiology*

Stromal interaction molecules (STIM)s are Ca²⁺ sensors in internal Ca²⁺ stores of the endoplasmic reticulum. They activate the store-operated Ca²⁺ channels, which are the main source of Ca²⁺ entry in non-excitable cells. Moreover, STIM proteins interact with other Ca²⁺ channel subunits and active transporters, making STIMs an important intermediate molecule in orchestrating a wide variety of Ca²⁺ influxes into excitable cells. Nevertheless, little is known about the role of STIM proteins in brain functioning. Being involved in many signaling pathways, STIMs replenish internal Ca²⁺ stores in neurons and mediate synaptic transmission and neuronal excitability. Ca²⁺ dyshomeostasis is a signature of many pathological conditions of the brain, including neurodegenerative diseases, injuries, stroke, and epilepsy. STIMs play a role in these disturbances not only by supporting abnormal store-operated Ca²⁺ entry but also by regulating Ca²⁺ influx through other channels. Here, we review the present knowledge of STIMs in neurons and their involvement in brain pathology.
Neurons/metabolism* ; Animals ; Humans ; Calcium/metabolism* ; Stromal Interaction Molecules/metabolism* ; Calcium Signaling/physiology* ; Calcium Channels/metabolism* ; Brain/metabolism*