Abstract：
:Understanding the transcriptional changes that are engaged in stress resilience may reveal novel antidepressant targets. Here we use gene co-expression analysis of RNA-sequencing data from brains of resilient mice to identify a gene network that is unique to resilience. Zfp189, which encodes a previously unstudied zinc finger protein, is the highest-ranked key driver gene in the network, and overexpression of Zfp189 in prefrontal cortical neurons preferentially activates this network and promotes behavioral resilience. The transcription factor CREB is a predicted upstream regulator of this network and binds to the Zfp189 promoter. To probe CREB-Zfp189 interactions, we employ CRISPR-mediated locus-specific transcriptional reprogramming to direct CREB or G9a (a repressive histone methyltransferase) to the Zfp189 promoter in prefrontal cortex neurons. Induction of Zfp189 with site-specific CREB is pro-resilient, whereas suppressing Zfp189 expression with G9a increases susceptibility. These findings reveal an essential role for Zfp189 and CREB-Zfp189 interactions in mediating a central transcriptional network of resilience.
journal_name
Nat Neuroscijournal_title
Nature neuroscienceauthors
Lorsch ZS,Hamilton PJ,Ramakrishnan A,Parise EM,Salery M,Wright WJ,Lepack AE,Mews P,Issler O,McKenzie A,Zhou X,Parise LF,Pirpinias ST,Ortiz Torres I,Kronman HG,Montgomery SE,Loh YE,Labonté B,Conkey A,Symonds AE,Nevdoi
10.1038/s41593-019-0462-8subject
Has Abstractpub_date
2019-09-01 00:00:00pages
1413-1423issue
9eissn
1097-6256issn
1546-1726pii
10.1038/s41593-019-0462-8journal_volume
22pub_type
杂志文章abstract：:Using multimodal neuroimaging in humans, we demonstrate specific interactions between prefrontal activity and midbrain dopaminergic synthesis. A common V(108/158)M substitution in the gene for catecholamine-O-methyltransferase (COMT), an important enzyme regulating prefrontal dopamine turnover, predicted reduced dopam...
journal_title：Nature neuroscience
pub_type： 杂志文章
doi：10.1038/nn1438
更新日期：2005-05-01 00:00:00
abstract：:We delineated a heritable phenotype resulting from the self-administration of cocaine in rats. We observed delayed acquisition and reduced maintenance of cocaine self-administration in male, but not female, offspring of sires that self-administered cocaine. Brain-derived neurotrophic factor (Bdnf) mRNA and BDNF protei...
journal_title：Nature neuroscience
pub_type： 杂志文章
doi：10.1038/nn.3280
更新日期：2013-01-01 00:00:00
abstract：:Olfaction has often been described as a ‘synthetic’ sense. A study now reveals a surprising capacity to resolve individual odorants in complex mixtures, with implications for how the nervous system recognizes objects. ...
journal_title：Nature neuroscience
pub_type： 评论,杂志文章
doi：10.1038/nn.3796
更新日期：2014-09-01 00:00:00
abstract：:Neuroscientists increasingly analyze the joint activity of multineuron recordings to identify population-level structures believed to be significant and scientifically novel. Claims of significant population structure support hypotheses in many brain areas. However, these claims require first investigating the possibi...
journal_title：Nature neuroscience
pub_type： 杂志文章
doi：10.1038/nn.4617
更新日期：2017-09-01 00:00:00
abstract：:En route to their target, pioneering motor growth cones repeatedly encounter choice points at which they make pathway decisions. In the zebrafish mutant unplugged, two of the three segmental motor axons make incorrect decisions at a somitic choice point. Using positional cloning, we show here that unplugged encodes a ...
journal_title：Nature neuroscience
pub_type： 杂志文章
doi：10.1038/nn1350
更新日期：2004-12-01 00:00:00
abstract：:We examined the contribution of 5-HT1A autoreceptors (with [11C]WAY100635 positron emission tomography) to amygdala reactivity (with blood oxygenation level-dependent functional magnetic resonance imaging) in 20 healthy adult volunteers. We found a significant inverse relationship wherein 5-HT1A autoreceptor density p...
journal_title：Nature neuroscience
pub_type： 杂志文章
doi：10.1038/nn1780
更新日期：2006-11-01 00:00:00
abstract：:Shared neural variability is ubiquitous in cortical populations. While this variability is presumed to arise from overlapping synaptic input, its precise relationship to local circuit architecture remains unclear. We combine computational models and in vivo recordings to study the relationship between the spatial stru...
journal_title：Nature neuroscience
pub_type： 杂志文章
doi：10.1038/nn.4433
更新日期：2017-01-01 00:00:00
abstract：:By combining computational, morphological, and functional analyses, this study relates latent markers of associative threat learning to overt post-traumatic stress disorder (PTSD) symptoms in combat veterans. Using reversal learning, we found that symptomatic veterans showed greater physiological adjustment to cues th...
journal_title：Nature neuroscience
pub_type： 杂志文章
doi：10.1038/s41593-018-0315-x
更新日期：2019-03-01 00:00:00
abstract：:The primate superior colliculus (SC) is a midbrain nucleus crucial for the control of rapid eye movements (saccades). Its neurons are topographically arranged over the rostrocaudal and mediolateral extent of its deeper layers so that saccade metrics (amplitude and direction) are coded in terms of the location of activ...
journal_title：Nature neuroscience
pub_type： 杂志文章
doi：10.1038/nn727
更新日期：2001-10-01 00:00:00
abstract：:Accumulation of abnormally phosphorylated TDP-43 (pTDP-43) is the main pathology in affected neurons of people with amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). Morphological diversity and neuroanatomical distribution of pTDP-43 accumulations allowed classification of FTLD cases in...
journal_title：Nature neuroscience
pub_type： 杂志文章
doi：10.1038/s41593-018-0294-y
更新日期：2019-01-01 00:00:00
abstract：:Humans exhibit a remarkable degree of resilience in the face of extreme stress, with most resisting the development of neuropsychiatric disorders. Over the past 5 years, there has been increasing interest in the active, adaptive coping mechanisms of resilience; however, in humans, most published work focuses on correl...
journal_title：Nature neuroscience
pub_type： 杂志文章,评审
doi：10.1038/nn.3234
更新日期：2012-11-01 00:00:00
abstract：:Specialization and hierarchy are organizing principles for primate cortex, yet there is little direct evidence for how cortical areas are specialized in the temporal domain. We measured timescales of intrinsic fluctuations in spiking activity across areas and found a hierarchical ordering, with sensory and prefrontal ...
journal_title：Nature neuroscience
pub_type： 杂志文章
doi：10.1038/nn.3862
更新日期：2014-12-01 00:00:00
abstract：:Mutations in copper/zinc superoxide dismutase 1 (SOD1), primary causes of human amyotrophic lateral sclerosis (ALS), provoke motor neuron death through an unidentified toxic property. The known neurofilament-dependent slowing of axonal transport, combined with the prominent misaccumulation of neurofilaments in ALS, su...
journal_title：Nature neuroscience
pub_type： 杂志文章
doi：10.1038/4553
更新日期：1999-01-01 00:00:00
abstract：:Remembering a past experience can, surprisingly, cause forgetting. Forgetting arises when other competing traces interfere with retrieval and inhibitory control mechanisms are engaged to suppress the distraction they cause. This form of forgetting is considered to be adaptive because it reduces future interference. Th...
journal_title：Nature neuroscience
pub_type： 杂志文章
doi：10.1038/nn.3973
更新日期：2015-04-01 00:00:00
abstract：:Humans and other primates sample the visual environment using saccadic eye movements that shift a high-resolution fovea toward regions of interest to create a clear perception of a scene across fixations. Many mammals, however, like mice, lack a fovea, which raises the question of why they make saccades. Here we descr...
journal_title：Nature neuroscience
pub_type： 杂志文章
doi：10.1038/s41593-018-0255-5
更新日期：2018-11-01 00:00:00
abstract：:Leptin regulates energy balance. However, knowledge of the critical intracellular transducers of leptin signaling remains incomplete. We found that Rho-kinase 1 (ROCK1) regulates leptin action on body weight homeostasis by activating JAK2, an initial trigger of leptin receptor signaling. Leptin promoted the physical i...
journal_title：Nature neuroscience
pub_type： 杂志文章
doi：10.1038/nn.3207
更新日期：2012-10-01 00:00:00
abstract：:The sensing of circulating nutrients within the mediobasal hypothalamus may be critical for energy homeostasis. To induce a sustained impairment in hypothalamic nutrient sensing, adeno-associated viruses (AAV) expressing malonyl-coenzyme A decarboxylase (MCD; an enzyme involved in the degradation of malonyl coenzyme A...
journal_title：Nature neuroscience
pub_type： 杂志文章
doi：10.1038/nn1626
更新日期：2006-02-01 00:00:00
abstract：:The 'cognitive map' hypothesis proposes that brain builds a unified representation of the spatial environment to support memory and guide future action. Forty years of electrophysiological research in rodents suggest that cognitive maps are neurally instantiated by place, grid, border and head direction cells in the h...
journal_title：Nature neuroscience
pub_type： 杂志文章,评审
doi：10.1038/nn.4656
更新日期：2017-10-26 00:00:00
abstract：:Individuals' risk attitudes are known to guide choices about uncertain options. However, in the presence of others' decisions, these choices can be swayed and manifest as riskier or safer behavior than one would express alone. To test the mechanisms underlying effective social 'nudges' in human decision-making, we use...
journal_title：Nature neuroscience
pub_type： 杂志文章
doi：10.1038/nn.4022
更新日期：2015-06-01 00:00:00
abstract：:The painful sensations produced by a laceration, freeze, burn, muscle strain or internal injury are readily distinguishable because each is characterized by a particular sensory quality such as sharp, aching, burning or prickling. We propose that there are specific neural correlates of each pain quality, and here we u...
journal_title：Nature neuroscience
pub_type： 杂志文章
doi：10.1038/nn955
更新日期：2002-11-01 00:00:00
abstract：:Electrophysiological connectivity patterns in cortex often have a few strong connections, which are sometimes bidirectional, among a lot of weak connections. To explain these connectivity patterns, we created a model of spike timing-dependent plasticity (STDP) in which synaptic changes depend on presynaptic spike arri...
journal_title：Nature neuroscience
pub_type： 杂志文章
doi：10.1038/nn.2479
更新日期：2010-03-01 00:00:00
abstract：:Microcircuits composed of principal neuron and interneuron dendrites have an important role in shaping the representation of sensory information in the olfactory bulb. Here we establish the physiological features governing synaptic signaling in dendrodendritic microcircuits of olfactory bulb glomeruli. We show that de...
journal_title：Nature neuroscience
pub_type： 杂志文章
doi：10.1038/nn1403
更新日期：2005-03-01 00:00:00
abstract：:Loss of noradrenergic locus coeruleus (LC) neurons is a prominent feature of aging-related neurodegenerative diseases, such as Parkinson's disease (PD). The basis of this vulnerability is not understood. To explore possible physiological determinants, we studied LC neurons using electrophysiological and optical approa...
journal_title：Nature neuroscience
pub_type： 杂志文章
doi：10.1038/nn.3717
更新日期：2014-06-01 00:00:00
abstract：:Central pattern generators (CPGs) are spinal neuronal networks required for locomotion. Glutamatergic neurons have been implicated as being important for intrinsic rhythm generation in the CPG and for the command signal for initiating locomotion, although this has not been demonstrated directly. We used a newly genera...
journal_title：Nature neuroscience
pub_type： 杂志文章
doi：10.1038/nn.2482
更新日期：2010-02-01 00:00:00
abstract：:Accurate optical reporting of electrical activity in genetically defined neuronal populations is a long-standing goal in neuroscience. We developed Accelerated Sensor of Action Potentials 1 (ASAP1), a voltage sensor design in which a circularly permuted green fluorescent protein is inserted in an extracellular loop of...
journal_title：Nature neuroscience
pub_type： 杂志文章
doi：10.1038/nn.3709
更新日期：2014-06-01 00:00:00
abstract：:Speech and vocal impairments characterize many neurological disorders. However, the neurogenetic mechanisms of these disorders are not well understood, and current animal models do not have the necessary circuitry to recapitulate vocal learning deficits. We developed germline transgenic songbirds, zebra finches (Tanei...
journal_title：Nature neuroscience
pub_type： 杂志文章
doi：10.1038/nn.4133
更新日期：2015-11-01 00:00:00
abstract：:Very little is known about how stimuli that are typically not rich in sugars, such as beer, trigger attractive gustatory responses in Drosophila. We identified a member of the gustatory receptor family, Gr64e, as a receptor that is required for feeding preference for beer and other sources that have fermenting yeast. ...
journal_title：Nature neuroscience
pub_type： 杂志文章
doi：10.1038/nn.2944
更新日期：2011-11-06 00:00:00
abstract：:Despite the numerous examples of anticipatory cognitive processes at micro and macro levels in many animal species, the idea that anticipation of specific words plays an integral role in real-time language processing has been contentious. Here we exploited a phonological regularity of English indefinite articles ('an'...
journal_title：Nature neuroscience
pub_type： 杂志文章
doi：10.1038/nn1504
更新日期：2005-08-01 00:00:00
abstract：:Dopamine signaling is implicated in reinforcement learning, but the neural substrates targeted by dopamine are poorly understood. We bypassed dopamine signaling itself and tested how optogenetic activation of dopamine D1 or D2 receptor–expressing striatal projection neurons influenced reinforcement learning in mice. S...
journal_title：Nature neuroscience
pub_type： 杂志文章
doi：10.1038/nn.3100
更新日期：2012-06-01 00:00:00
abstract：:Population coding is widely regarded as an important mechanism for achieving reliable behavioral responses despite neuronal variability. However, standard reinforcement learning slows down with increasing population size, as the global reward signal becomes less and less related to the performance of any single neuron...
journal_title：Nature neuroscience
pub_type： 杂志文章
doi：10.1038/nn.2264
更新日期：2009-03-01 00:00:00
