Trends in Neurosciences最新文献

Cortical responses to stimuli vary dependingon context and expectation. Adding insight into this process, Furutachi et al. recently demonstrated that higher-order thalamic input to visual cortex cooperates with interneurons to augment responses to unexpected stimuli, consistent with a body of literature implicating top-down modulation and local inhibition in predictive processing.

The ability to learn from experience that certain cues and situations are associated with threats or safety is crucial for survival and adaptive behavior. Understanding the neural substrates of threat and safety learning has high clinical significance because deficits in these forms of learning characterize anxiety disorders. Traditionally, dopamine neurons were thought to uniformly support reward learning by signaling reward prediction errors. However, the dopamine system is functionally more diverse than was initially appreciated and is also critical for processing threat and safety. In this review, I highlight recent studies demonstrating that dopamine neurons generate prediction errors for threat and safety, and describe how dopamine projections to the amygdala, medial prefrontal cortex (mPFC), and striatum regulate associative threat and safety learning.

Retinal ganglion cells (RGCs) are the brain's gateway for vision, and their degeneration underlies several blinding diseases. RGCs interact with other neuronal cell types, microglia, and astrocytes in the retina and in the brain. Much knowledge has been gained about RGCs and glia from mice and other model organisms, often with the assumption that certain aspects of their biology may be conserved in humans. However, RGCs vary considerably between species, which could affect how they interact with their neuronal and glial partners. This review details which RGC and glial features are conserved between mice, humans, and primates, and which differ. We also discuss experimental approaches for studying human and primate RGCs. These strategies will help to bridge the gap between rodent and human RGC studies and increase study translatability to guide future therapeutic strategies.

Central nervous system-associated macrophages (CAMs) are a unique subset of immune cells located at the interface between the blood and the brain parenchyma. In a recent study in mice, Levard and colleagues found that CAMs regulate immune cell trafficking, endothelial activation, and antigen presentation following stroke exclusively in aged animals, underscoring the importance of using translationally relevant models for studying age-related diseases.

Injury to the central nervous system (CNS) often results in permanent neurological impairments because axons fail to regenerate and re-establish lost synaptic contacts. By contrast, peripheral neurons can activate a pro-regenerative program and regenerate following a nerve lesion. This relies on an intricate intracellular communication system between the severed axon and the cell body. Locally activated signaling molecules are retrogradely transported to the soma to promote the epigenetic and transcriptional changes required for the injured neuron to regain growth competence. These signaling events rely heavily on intra-axonal translation and mitochondrial trafficking into the severed axon. Here, we discuss the interplay between these mechanisms and the main intrinsic barriers to axonal regeneration. We also examine the potential of manipulating these processes for driving CNS repair.

Chronic stress and the accompanying long-term elevation of glucocorticoids (GCs), the stress hormones of the body, increase the risk and accelerate the progression of Alzheimer's disease (AD). Signatures of AD include intracellular tau (MAPT) tangles, extracellular amyloid β (Aβ) plaques, and neuroinflammation. A growing body of work indicates that stress and GCs initiate cellular processes underlying these pathologies through dysregulation of protein homeostasis and trafficking, mitochondrial bioenergetics, and response to damage-associated stimuli. In this review, we integrate findings from mechanistic studies in rodent and cellular models, wherein defined chronic stress protocols or GC administration have been shown to elicit AD-related pathology. We specifically discuss the effects of chronic stress and GCs on tau pathogenesis, including hyperphosphorylation, aggregation, and spreading, amyloid precursor protein (APP) processing and trafficking culminating in Aβ production, immune priming by proinflammatory cytokines and disease-associated molecular patterns, and alterations to glial cell and blood-brain barrier (BBB) function.

Recent research by Parks, Schneider, and colleagues demonstrates that brain states during rodent sleep can be predicted from neural activity on millisecond and micrometer scales. These findings contradict the traditional view that defines sleep by brain-wide oscillations. Instead, this work posits that nonoscillatory activity governs different brain states.

Antimicrobial peptides (AMPs), a collection of small proteins with important roles in classical innate immunity, have been extensively studied in multiple organisms, particularly in Drosophila melanogaster. Advances in CRISPR/Cas9 genome editing have allowed individual AMP functions to be dissected, revealing specific and selective roles in host defense. Recent findings have also revealed many unexpected contributions of endogenous AMPs to neuronal functions and neurodegenerative diseases, and have shed light on the intersections between innate immunity and neurobiology. We explore the intricate relationships between AMPs and sleep regulation, memory formation, as well as traumatic brain injury and several neurodegenerative diseases such as Alzheimer's disease (AD), frontotemporal dementia (FTD), and Parkinson's disease (PD). Understanding the diverse functions of AMPs opens new avenues for neuroinflammation and neurodegenerative disease research and potential therapeutic development.

Across species, navigation is crucial for finding both resources and shelter. In vertebrates, the hippocampus supports memory-guided goal-directed navigation, whereas in arthropods the central complex supports similar functions. A growing literature is revealing similarities and differences in the organization and function of these brain regions. We review current knowledge about how each structure supports goal-directed navigation by building internal representations of the position or orientation of an animal in space, and of the location or direction of potential goals. We describe input pathways to each structure - medial and lateral entorhinal cortex in vertebrates, and columnar and tangential neurons in insects - that primarily encode spatial and non-spatial information, respectively. Finally, we highlight similarities and differences in spatial encoding across clades and suggest experimental approaches to compare coding principles and behavioral capabilities across species. Such a comparative approach can provide new insights into the neural basis of spatial navigation and neural computation.

RNA-binding proteins (RBPs) can undergo phase separation and form condensates, processes that, in turn, can be critical for their functionality. In a recent study, Huang, Ellis, and colleagues show that cellular stress can trigger transient alterations in nuclear TAR DNA-binding protein 43 (TDP-43), leading to changes crucial for proper neuronal function. These findings have implications for understanding neurological TDP-43 proteinopathies.