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Activity-dependent transcription has emerged as a major source of gene products that regulate neuronal excitability, connectivity, and synaptic properties. However, the elongation rate of RNA polymerases imposes a significant temporal constraint for transcript synthesis, in particular for long genes where new synthesis requires hours. Here we reveal a novel, transcription-independent mechanism that...
Electrical brain stimulation (EBS) complements neural measurements by probing the causal relationship between brain and perception, cognition, and action. Many fundamental questions about EBS remain unanswered, including the spatial extent of cortex responsive to stimulation, and the relationship between the circuitry engaged by EBS and the types of neural responses elicited by sensory stimulation...
Sensing the level of oxygen in the external and internal environments is essential for survival. Organisms have evolved multiple mechanisms to sense oxygen. No function in oxygen sensing has been attributed to any mammalian olfactory system. Here, we demonstrate that low environmental oxygen directly activates a subpopulation of sensory neurons in the mouse main olfactory epithelium. These neurons...
Generic spinal motor neuron identity is established by cooperative binding of programming transcription factors (TFs), Isl1 and Lhx3, to motor-neuron-specific enhancers. How expression of effector genes is maintained following downregulation of programming TFs in maturing neurons remains unknown. High-resolution exonuclease (ChIP-exo) mapping revealed that the majority of enhancers established by...
Mitochondrial transport is crucial for neuronal and axonal physiology. However, whether and how it impacts neuronal injury responses, such as neuronal survival and axon regeneration, remain largely unknown. In an established mouse model with robust axon regeneration, we show that Armcx1, a mammalian-specific gene encoding a mitochondria-localized protein, is upregulated after axotomy in this high...
While beneficial effects of fasting on organismal function and health are well appreciated, we know little about the molecular details of how fasting influences synaptic function and plasticity. Our genetic and electrophysiological experiments demonstrate that acute fasting blocks retrograde synaptic enhancement that is normally triggered as a result of reduction in postsynaptic receptor function...
Frontal cortex plays a central role in the control of voluntary movements, which are typically guided by sensory input. Here, we investigate the function of mouse whisker primary motor cortex (wM1), a frontal region defined by dense innervation from whisker primary somatosensory cortex (wS1). Optogenetic stimulation of wM1 evokes rhythmic whisker protraction (whisking), whereas optogenetic inactivation...
A critical feature of neural networks is that they balance excitation and inhibition to prevent pathological dysfunction. How this is achieved is largely unknown, although deficits in the balance contribute to many neurological disorders. We show here that a microRNA (miR-101) is a key orchestrator of this essential feature, shaping the developing network to constrain excitation in the adult. Transient...
In this issue of Neuron, Han et al. (2016) and Cartoni et al. (2016) define a critical role of mitochondrial transport for successful axon regeneration after injury and provide new insights into intrinsic mechanisms controlling neuronal regeneration capacity in worms and mice.
Yang et al. (2016) show that transplantation of GABAergic inhibitory neurons into the amygdala boosts the persistence of fear extinction in mice. Transplantation was found to degrade perineuronal nets on endogenous inhibitory neurons and enhance synaptic plasticity in host amygdala.
Axon regeneration is essential to restore the nervous system after axon injury. However, the neuronal cell biology that underlies axon regeneration is incompletely understood. Here we use in vivo, single-neuron analysis to investigate the relationship between nerve injury, mitochondrial localization, and axon regeneration. Mitochondria translocate into injured axons so that average mitochondria density...
Rhee et al. (2016) in this issue of Neuron and Velasco et al. (2016) in Cell Stem Cell find that the activity of transcription factors binding sequentially to a series of transient early and late enhancers directs gene expression that is essential for motor neuron differentiation and function.
Hexanucleotide repeat expansion in the bi-directionally transcribed C9orf72 gene is the most frequent cause of familial ALS and frontotemporal dementia (FTD). Kramer et al. (2016) report in Science that targeted reduction in the transcription elongation factor SUPT4H1/SUPT5H reduces both sense and antisense repeat-containing RNAs and their associated neurodegeneration.
Astrocytes exist throughout the nervous system and are proposed to affect neural circuits and behavior. However, studying astrocytes has proven difficult because of the lack of tools permitting astrocyte-selective genetic manipulations. Here, we report the generation of Aldh1l1-Cre/ERT2 transgenic mice to selectively target astrocytes in vivo. We characterized Aldh1l1-Cre/ERT2 mice using imaging,...
Making decisions in uncertain environments often requires combining multiple pieces of ambiguous information from external cues. In such conditions, human choices resemble optimal Bayesian inference, but typically show a large suboptimal variability whose origin remains poorly understood. In particular, this choice suboptimality might arise from imperfections in mental inference rather than in peripheral...
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