Neuroscientist最新文献

Spinal cord injury leads to disruption in autonomic control resulting in cardiovascular, bowel, and lower urinary tract dysfunctions, all of which significantly reduce health-related quality of life. Although spinal cord stimulation shows promise for promoting autonomic recovery, the underlying mechanisms are unclear. Based on current preclinical and clinical evidence, this narrative review provides the most plausible mechanisms underlying the effects of spinal cord stimulation for autonomic recovery, including activation of the somatoautonomic reflex and induction of neuroplastic changes in the spinal cord. Areas where evidence is limited are highlighted in an effort to guide the scientific community to further explore these mechanisms and advance the clinical translation of spinal cord stimulation for autonomic recovery.

The mesencephalic locomotor region (MLR) controls locomotion in vertebrates. In humans with Parkinson disease, locomotor deficits are increasingly associated with decreased activity in the MLR. This brainstem region, commonly considered to include the cuneiform and pedunculopontine nuclei, has been explored as a target for deep brain stimulation to improve locomotor function, but the results are variable, from modest to promising. However, the MLR is a heterogeneous structure, and identification of the best cell type to target is only beginning. Here, I review the studies that uncovered the role of genetically defined MLR cell types, and I highlight the cells whose activation improves locomotor function in animal models of Parkinson disease. The promising cell types to activate comprise some glutamatergic neurons in the cuneiform and caudal pedunculopontine nuclei, as well as some cholinergic neurons of the pedunculopontine nucleus. Activation of MLR GABAergic neurons should be avoided, since they stop locomotion or evoke bouts flanked with numerous stops. MLR is also considered a potential target in spinal cord injury, supranuclear palsy, primary progressive freezing of gait, or stroke. Better targeting of the MLR cell types should be achieved through optimized deep brain stimulation protocols, pharmacotherapy, or the development of optogenetics for human use.

The amygdala has long held the center seat in the neural basis of threat conditioning. However, a rapidly growing literature has elucidated extra-amygdala circuits in this process, highlighting the sensory cortex for its critical role in the mnemonic aspect of the process. While this literature is largely focused on the auditory system, substantial human and rodent findings on the olfactory system have emerged. The unique nature of the olfactory neuroanatomy and its intimate association with emotion compels a review of this recent literature to illuminate its special contribution to threat memory. Here, integrating recent evidence in humans and animal models, we posit that the olfactory (piriform) cortex is a primary and necessary component of the distributed threat memory network, supporting mnemonic ensemble coding of acquired threat. We further highlight the basic circuit architecture of the piriform cortex characterized by distributed, auto-associative connections, which is prime for highly efficient content-addressable memory computing to support threat memory. Given the primordial role of the piriform cortex in cortical evolution and its simple, well-defined circuits, we propose that olfaction can be a model system for understanding (transmodal) sensory cortical mechanisms underlying threat memory.

The brain is designed not only with molecules and cellular processes that help to form memories but also with molecules and cellular processes that suppress the formation and retention of memory. The latter processes are critical for an efficient memory management system, given the vast amount of information that each person experiences in their daily activities and that most of this information becomes irrelevant with time. Thus, efficiency dictates that the brain should have processes for selecting the most critical information for storage and suppressing the irrelevant or forgetting it later should it escape the initial filters. Such memory suppressor molecules and processes are revealed by genetic or pharmacologic insults that lead to enhanced memory expression. We review here the predominant memory suppressor molecules and processes that have recently been discovered. They are diverse, as expected, because the brain is complex and employs many different strategies and mechanisms to form memories. They include the gene-repressive actions of small noncoding RNAs, repressors of protein synthesis, cAMP-mediated gene expression pathways, inter- and intracellular signaling pathways for normal forgetting, and others. A deep understanding of memory suppressor molecules and processes is necessary to fully comprehend how the brain forms, stabilizes, and retrieves memories and to reveal how brain disorders disrupt memory.

The existence of neurogenesis in the adult human hippocampus has been under considerable debate within the past three decades due to the diverging conclusions originating mostly from immunohistochemistry studies. While some of these reports conclude that hippocampal neurogenesis in humans occurs throughout physiologic aging, others indicate that this phenomenon ends by early childhood. More recently, some groups have adopted next-generation sequencing technologies to characterize with more acuity the extent of this phenomenon in humans. Here, we review the current state of research on adult hippocampal neurogenesis in the human brain with an emphasis on the challenges and limitations of using immunohistochemistry and next-generation sequencing technologies for its study.

Scientific theories on the functioning and dysfunction of the human brain require an understanding of its development-before and after birth and through maturation to adulthood-and its evolution. Here we bring together several accounts of human brain evolution by focusing on the central role of oxygen and brain metabolism. We argue that evolutionary expansion of human transmodal association cortices exceeded the capacity of oxygen delivery by the vascular system, which led these brain tissues to rely on nonoxidative glycolysis for additional energy supply. We draw a link between the resulting lower oxygen tension and its effect on cytoarchitecture, which we posit as a key driver of genetic developmental programs for the human brain-favoring lower intracortical myelination and the presence of biosynthetic materials for synapse turnover. Across biological and temporal scales, this protracted capacity for neural plasticity sets the conditions for cognitive flexibility and ongoing learning, supporting complex group dynamics and intergenerational learning that in turn enabled improved nutrition to fuel the metabolic costs of further cortical expansion. Our proposed model delineates explicit mechanistic links among metabolism, molecular and cellular brain heterogeneity, and behavior, which may lead toward a clearer understanding of brain development and its disorders.

Extracellular vesicles (EVs) are secreted from most, if not all, cell types and are implicated in short- and long-distance signaling throughout the body. EVs are also secreted from neurons and represent an emergent neuronal communication platform. Understanding the functional implications of EV signaling to recipient neurons and glia requires understanding the cell biology involved in EV biogenesis, cargo loading, secretion, uptake, and signal transduction in the recipient cell. Here we review these major questions of EV biology while highlighting recent new insights and examples within the nervous system, such as modulating synaptic function or morphogenesis in recipient neurons.