Interactions between brain-resident and peripheral infiltrated immune cells are thought to contribute to neuroplasticity after cerebral ischemia. However, conventional bulk sequencing makes it challenging to depict this complex immune network. Using single-cell RNA sequencing, we mapped compositional and transcriptional features of peri-infarct immune cells. Microglia were the predominant cell type in the peri-infarct region, displaying a more diverse activation pattern than the typical pro- and anti-inflammatory state, with axon tract-associated microglia (ATMs) being associated with neuronal regeneration. Trajectory inference suggested that infiltrated monocyte-derived macrophages (MDMs) exhibited a gradual fate trajectory transition to activated MDMs. Inter-cellular crosstalk between MDMs and microglia orchestrated anti-inflammatory and repair-promoting microglia phenotypes and promoted post-stroke neurogenesis, with SOX2 and related Akt/CREB signaling as the underlying mechanisms. This description of the brain's immune landscape and its relationship with neurogenesis provides new insight into promoting neural repair by regulating neuroinflammatory responses.
Humans ; Ischemic Stroke ; Brain/metabolism* ; Macrophages ; Brain Ischemia/metabolism* ; Microglia/metabolism* ; Gene Expression Profiling ; Anti-Inflammatory Agents ; Neuronal Plasticity/physiology* ; Infarction/metabolism*

For decades, memory research has centered on the role of neurons, which do not function in isolation. However, astrocytes play important roles in regulating neuronal recruitment and function at the local and network levels, forming the basis for information processing as well as memory formation and storage. In this review, we discuss the role of astrocytes in memory functions and their cellular underpinnings at multiple time points. We summarize important breakthroughs and controversies in the field as well as potential avenues to further illuminate the role of astrocytes in memory processes.
Astrocytes ; Neuronal Plasticity/physiology* ; Memory/physiology* ; Neurons/physiology* ; Cognition/physiology*

Crossmodal information processing in sensory cortices has been reported in sparsely distributed neurons under normal conditions and can undergo experience- or activity-induced plasticity. Given the potential role in brain function as indicated by previous reports, crossmodal connectivity in the sensory cortex needs to be further explored. Using perforated whole-cell recording in anesthetized adult rats, we found that almost all neurons recorded in the primary somatosensory, auditory, and visual cortices exhibited significant membrane-potential responses to crossmodal stimulation, as recorded when brain activity states were pharmacologically down-regulated in light anesthesia. These crossmodal cortical responses were excitatory and subthreshold, and further seemed to be relayed primarily by the sensory thalamus, but not the sensory cortex, of the stimulated modality. Our experiments indicate a sensory cortical presence of widespread excitatory crossmodal inputs, which might play roles in brain functions involving crossmodal information processing or plasticity.
Animals ; Auditory Cortex/physiology* ; Neuronal Plasticity/physiology* ; Neurons ; Rats ; Thalamus ; Visual Cortex/physiology*

The back-propagating action potential (bpAP) is crucial for neuronal signal integration and synaptic plasticity in dendritic trees. Its properties (velocity and amplitude) can be affected by dendritic morphology. Due to limited spatial resolution, it has been difficult to explore the specific propagation process of bpAPs along dendrites and examine the influence of dendritic morphology, such as the dendrite diameter and branching pattern, using patch-clamp recording. By taking advantage of Optopatch, an all-optical electrophysiological method, we made detailed recordings of the real-time propagation of bpAPs in dendritic trees. We found that the velocity of bpAPs was not uniform in a single dendrite, and the bpAP velocity differed among distinct dendrites of the same neuron. The velocity of a bpAP was positively correlated with the diameter of the dendrite on which it propagated. In addition, when bpAPs passed through a dendritic branch point, their velocity decreased significantly. Similar to velocity, the amplitude of bpAPs was also positively correlated with dendritic diameter, and the attenuation patterns of bpAPs differed among different dendrites. Simulation results from neuron models with different dendritic morphology corresponded well with the experimental results. These findings indicate that the dendritic diameter and branching pattern significantly influence the properties of bpAPs. The diversity among the bpAPs recorded in different neurons was mainly due to differences in dendritic morphology. These results may inspire the construction of neuronal models to predict the propagation of bpAPs in dendrites with enormous variation in morphology, to further illuminate the role of bpAPs in neuronal communication.
Action Potentials/physiology* ; Dendrites/physiology* ; Neurons/physiology* ; Neuronal Plasticity ; Pyramidal Cells/physiology*

Synaptic cell adhesion molecules (CAMs) are a type of membrane surface glycoproteins that mediate the structural and functional interactions between pre- and post-synaptic sites. Synaptic CAMs dynamically regulate synaptic activity and plasticity, and their expression and function are modulated by environmental factors. Synaptic CAMs are also important effector molecules of stress response, and mediate the adverse impact of stress on cognition and emotion. In this review, we will summarize the recent progress on the role of synaptic CAMs in stress, and aim to provide insight into the molecular mechanisms and drug development of stress-related disorders.
Cell Adhesion ; Cell Adhesion Molecules ; physiology ; Humans ; Neuronal Plasticity ; Stress, Physiological ; Stress, Psychological ; Synapses

OBJECTIVE: To understand and analyze the rules of endurance exercise on the cerebral cortex adaptive mechanism in aged rats. METHODS: In this study, 3-month-old (n=20), 13-month-old (n=24) and 23-month-old (n=24) specific-pathogen free (SPF) male Sprague-Dawley Rat (SD) rats were divided into young (Y-SED), middle-aged (M-SED) and old-aged (O-SED) sedentary control group, and the corresponding Y-EX, M-EX and O-EX in the endurance exercise runner group. The 10-weeks of regular moderate-intensity aerobic exercise intervention were carried out in the endurance exercise runner group. The exercise mode is treadmill exercise (slope 0), and the exercise intensity gradually increases from 60%～65% of the maximum oxygen consumption (V·O) to 70%～75%, and the exercise time is 10 weeks. Hematoxylin and eosin (HE) staining was used to detect age-related morphological changes. The expressions of superoxide dismutase(SOD) and brain-derived neurotrophic factor (BDNF) and the expressions of synapsin 1 (SYN1) and Ca/calmodulin- dependent protein kinases IIα (CaMK IIα) / AMP-activated protein kinase α1(AMPKα1) / mammalian target of rapamycin (mTOR) pathway -related genes were detected. RESULTS: The cerebral cortex structure of the rats in each group showed age-related aging changes, the expression of SOD in the cortex showed a gradual decline, the expression of BDNF showed an age-increasing trend, and the expression levels of SYN1 and CaMK IIα were increased with age. The changes in AMPKα1 and SirT2 and IP3R, AKT1 and mTOR mRNA levels were increased slightly in middle-aged rats and decreased in aged rats. Compared with the rats in each sedentary control group, the nucleus of the cerebral cortex was tightly arranged and the number of nuclei observed under the microscope was increased significantly in each exercise group. Exercise promoted the expressions of SOD, BDNF and synaptophysin SYN1 in the cortex of rats, and the expression levels of SOD and BDNF in aged rats were up-regulated significantly (P＜ 0.01). The expression level of SYN1 in rats was up-regulated significantly (P＜0.05) in the young and aged rats. The expression of CaMK IIα in the cortex of middle-aged and aged rats was up-regulated (P＜0.01), while the expression level of CaMK IIα in young rats was down-regulated (P＜0.01). Exercise could up-regulate the expression level of AMPKα1 in the cortex of young rats (P＜ 0.05), but not in middle-aged and old-age rats. Exercise could up-regulate the expression of SirT2 in the cortex of rats in all age groups (P＜0.05). Exercise up-regulated the expression of phosphoinositide 3-kinase (IP3R)/ protein kinase B 1(AKT1) /mTOR in the cortex of rats, among which young IP3R was significantly up-regulated (P＜0.01) in the young group, mTOR was significantly up-regulated in young and middle-aged group (P＜0.01), and mTOR was also significantly up-regulated in the aged group (P＜0.05). CONCLUSION Endurance exercise up-regulates BDNF expression, regulates CaMKIIα signaling, activates AMPK signaling pathway and IP3R / AKT1 / mTOR signaling pathway, and improves synaptic plasticity in the cortex.
Age Factors ; Animals ; Cerebral Cortex ; physiology ; Male ; Neuronal Plasticity ; Physical Conditioning, Animal ; Physical Endurance ; Rats ; Rats, Sprague-Dawley ; Signal Transduction

Spinal cord injury (SCI), which is much in the public eye, is still a refractory disease compromising the well-being of both patients and society. In spite of there being many methods dealing with the lesion, there is still a deficiency in comprehensive strategies covering all facets of this damage. Further, we should also mention the structure called the corticospinal tract (CST) which plays a crucial role in the motor responses of organisms, and it will be the focal point of our attention. In this review, we discuss a variety of strategies targeting different dimensions following SCI and some treatments that are especially efficacious to the CST are emphasized. Over recent decades, researchers have developed many effective tactics involving five approaches: (1) tackle more extensive regions; (2) provide a regenerative microenvironment; (3) provide a glial microenvironment; (4) transplantation; and (5) other auxiliary methods, for instance, rehabilitation training and electrical stimulation. We review the basic knowledge on this disease and correlative treatments. In addition, some well-formulated perspectives and hypotheses have been delineated. We emphasize that such a multifaceted problem needs combinatorial approaches, and we analyze some discrepancies in past studies. Finally, for the future, we present numerous brand-new latent tactics which have great promise for curbing SCI.
Animals ; Astrocytes/cytology* ; Axons/physiology* ; Cell Transplantation ; Disease Models, Animal ; Electric Stimulation ; Humans ; Microglia/cytology* ; Motor Neurons/cytology* ; Nerve Regeneration ; Neuroglia/cytology* ; Neuronal Plasticity ; Neurons/cytology* ; Oligodendroglia/cytology* ; Pyramidal Tracts/pathology* ; Recovery of Function ; Regenerative Medicine/methods* ; Spinal Cord Injuries/therapy*

Previously believed to solely play a supportive role in the central nervous system, astrocytes are now considered active players in normal brain function. Evidence in recent decades extends their contributions beyond the classically held brain glue role; it's now known that astrocytes act as a unique excitable component with functions extending into local network modulation, synaptic plasticity, and memory formation, and postinjury repair. In this review article, we highlight our growing understanding of astrocyte function and physiology, the increasing role of gliotransmitters in neuron-glia communication, and the role of astrocytes in modulating synaptic plasticity and cognitive function. Owing to the duality of both beneficial and deleterious roles attributed to astrocytes, we also discuss the implications of this new knowledge as it applies to neurological disorders including Alzheimer disease, epilepsy, and schizophrenia.
Adhesives* ; Alzheimer Disease ; Astrocytes* ; Brain ; Central Nervous System ; Cognition ; Epilepsy ; Memory ; Nervous System Diseases* ; Neuronal Plasticity* ; Physiology ; Schizophrenia

Sympathetic arborizations act as the essential efferent signals in regulating the metabolism of peripheral organs including white adipose tissues (WAT). However, whether these local neural structures would be of plastic nature, and how such plasticity might participate in specific metabolic events of WAT, remains largely uncharacterized. In this study, we exploit the new volume fluorescence-imaging technique to observe the significant, and also reversible, plasticity of intra-adipose sympathetic arborizations in mouse inguinal WAT in response to cold challenge. We demonstrate that this sympathetic plasticity depends on the cold-elicited signal of nerve growth factor (NGF) and TrkA receptor. Blockage of NGF or TrkA signaling suppresses intra-adipose sympathetic plasticity, and moreover, the cold-induced beiging process of WAT. Furthermore, we show that NGF expression in WAT depends on the catecholamine signal in cold challenge. We therefore reveal the key physiological relevance, together with the regulatory mechanism, of intra-adipose sympathetic plasticity in the WAT metabolism.
Adipose Tissue, Beige ; cytology ; diagnostic imaging ; innervation ; metabolism ; Animals ; Catecholamines ; metabolism ; Cold Temperature ; Imaging, Three-Dimensional ; Mice ; Nerve Growth Factor ; metabolism ; Neuronal Plasticity ; Receptor, trkA ; metabolism ; Signal Transduction ; Sympathetic Nervous System ; physiology

Animals ; Brain ; physiology ; Extinction, Psychological ; physiology ; Humans ; Long-Term Potentiation ; Long-Term Synaptic Depression ; Neural Pathways ; physiology ; Neuronal Plasticity ; Neurons ; physiology ; Receptors, AMPA ; physiology