Trends in Neurosciences最新文献

International consortia collaborating on the genetics of rare diseases have significantly boosted our understanding of inherited neurological disorders. Historical clinical classification boundaries were drawn between disorders with seemingly different etiologies, such as inherited peripheral neuropathies (IPNs), spastic paraplegias, and cerebellar ataxias. These clinically defined borders are being challenged by the identification of mutations in genes displaying wide phenotypic spectra and by shared pathomechanistic themes, which are valuable indications for therapy development. We highlight common cellular alterations that underlie this genetic landscape, including alteration of cytoskeleton, axonal transport, mitochondrial function, and DNA repair response. Finally, we discuss venues for future research using the long axonopathies of the PNS as a model to explore other neurogenetic disorders.

Our brains are good at detecting and learning associative structures; according to some linguistic theories, this capacity even constitutes a prerequisite for the development of syntax and compositionality in language and verbalized thought. I will argue that the search for associative motifs in input patterns is an evolutionary old brain function that enables contiguity in sensory perception and orientation in time and space. It has its origins in an elementary material property of cells that is particularly evident at chemical synapses: input-assigned calcium influx that activates calcium sensor proteins involved in memory storage. This machinery for the detection and learning of associative motifs generates knowledge about input relationships and integrates this knowledge into existing networks through updates in connectivity patterns.

In a recent study, Guo and colleagues characterised the function of an elusive endoplasmic reticulum (ER) anion channel protein, Chloride Channel CLiC Like 1 (CLCC1), and identified rare CLCC1 variants in people with amyotrophic lateral sclerosis (ALS). CLCC1 mutants disrupted ER function in vitro and promoted ALS-like pathology and neurodegeneration in mice. This work reveals a previously uncharacterised pathway involved in ER calcium release and highlights new pathogenic mechanisms underlying neurodegeneration.

Homeostatic reflexes are crucial for life, but the subpopulations of sensory neurons that stimulate these reflexes are largely unknown. A recent paper from Lovelace, Ma, and colleagues identified a population of sensory neurons in the cardiac ventricle that underlies the Bezold-Jarisch reflex and triggers syncope (fainting).

The impact of the COVID-19 pandemic on physical and mental health hardly need be reiterated. Yet, there are likely other indirect aftereffects of COVID-19 infection in addition to the direct effects. This article aims to initiate a conversation regarding difficult-to-capture outcomes of the pandemic that are relevant to researchers who test human participants. These considerations encourage collection of additional measures when assessing pre- versus postpandemic patterns of behavior.

Microglia are the primary immune cells of the CNS, contributing to both inflammatory damage and tissue repair in neurological disorder. In addition, emerging evidence highlights the role of homeostatic microglia in regulating neuronal activity, interacting with synapses, tuning neural circuits, and modulating behaviors. Herein, we review how microglia sense and regulate neuronal activity through synaptic interactions, thereby directly engaging with neural networks and behaviors. We discuss current studies utilizing microglial optogenetic and chemogenetic approaches to modulate adult neural circuits. These manipulations of microglia across different CNS regions lead to diverse behavioral consequences. We propose that spatial heterogeneity of microglia–neuron interaction lays the groundwork for understanding diverse functions of microglia in neural circuits and behaviors.

Post-traumatic stress disorder (PTSD) is characterized by altered emotional and behavioral responding following a traumatic event. In this article, we review the concepts of latent-state and model-based learning (i.e., learning and inferring abstract task representations) and discuss their relevance for clinical and neuroscience models of PTSD. Recent data demonstrate evidence for brain and behavioral biases in these learning processes in PTSD. These new data potentially recast excessive fear towards trauma cues as a problem in learning and updating abstract task representations, as opposed to traditional conceptualizations focused on stimulus-specific learning. Biases in latent-state and model-based learning may also be a common mechanism targeted in common therapies for PTSD. We highlight key knowledge gaps that need to be addressed to further elaborate how latent-state learning and its associated neurocircuitry mechanisms function in PTSD and how to optimize treatments to target these processes.