Neuroscience
-
In order for open science to reach its full potential to reduce barriers in science and increase access to the field, data and tools need to be accompanied by training and other supporting resources to make them truly accessible to prospective and new users. Further, these educational resources must be tailored to meet the needs of many different user profiles, such as neuroscientists of many specialties, computational scientists, and educators. In this article, we will describe some of the approaches the Allen Institute has taken to support working scientists, students, and educators at multiple career stages and paths to use our open science resources.
-
Astrocytes have been increasingly acknowledged to play active roles in regulating synaptic transmission and plasticity. Through a variety of metabotropic and ionotropic receptors expressed on their surface, astrocytes detect extracellular neurotransmitters, and in turn, release gliotransmitters to modify synaptic strength, while they can also alter neuronal membrane excitability by modulating extracellular ionic milieu. Given the seemingly large repertoire of synaptic modulation, when, where and how astrocytes interact with synapses remain to be fully understood. ⋯ Upon preventing astrocyte calcium signaling or blocking L-VGCCs, NMDA + glycine application triggers an increase, rather than a decrease, in the rate of spontaneous glutamate release, thereby shifting the presynaptic plasticity to promote an increase in strength. Our findings point to a crucial and surprising role of astrocytes in controlling the polarity of NMDA receptor and adenosine-dependent presynaptic plasticity. Such a pivotal mechanism unveils the power of astrocytes in regulating computations performed by neural circuits and is expected to profoundly impact cognitive processes.
-
Cell quiescence is an essential mechanism that allows cells to temporarily halt proliferation while preserving the potential to resume it at a later time. The molecular mechanisms underlying cell quiescence are complex and involve the regulation of various signaling pathways, transcription factors and epigenetic modifications. The importance of unveiling the mechanisms regulating the quiescent state is undeniable, as its long-term maintenance is key to sustain tissue homeostasis throughout life. ⋯ Differently from other non-proliferative states, quiescence is a reversible and tightly regulated condition that can re-activate to support the formation of new neurons throughout adult lifespan. Decoding its regulatory mechanisms in homeostasis and unveiling how it is modulated in the context of the aged brain or during tumorigenesis, could bring us closer to the development of new potential strategies to intervene in adult neurogenesis with therapeutic purposes. Starting with a general conceptualization of the quiescent state in different stem cell niches, we here review what we have learned about NSC quiescence in the SEZ, encompassing the experimental strategies used for its study, to end up discussing the modulation of quiescence in the context of a physiology or pathological NSC dysregulation.
-
Dopamine (DA) is a critical neuromodulator involved in various brain functions. To understand how DA regulates neural circuits and behaviors in the physiological and pathological conditions, it is essential to have tools that enable the direct detection of DA dynamics in vivo. Recently, genetically encoded DA sensors based on G protein-coupled receptors revolutionized this field, as it allows us to track in vivo DA dynamic with unprecedented spatial-temporal resolution, high molecular specificity, and sub-second kinetics. ⋯ Then we focus on the development of genetically encoded DA sensors and feature its significance to understanding dopaminergic neuromodulation across diverse behaviors and species. Finally, we present our perspectives about the future direction of the next-generation DA sensors and extend their potential applications. Overall, this review offers a comprehensive perspective on the past, present, and future of DA detection tools, with important implications for the study of DA functions in health and disease.