Publisher Correction: Three-dimensional genome restructuring across timescales of activity-induced neuronal gene expression.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Three-dimensional genome restructuring across timescales of activity-induced neuronal gene expression.

Neuronal activation induces rapid transcription of immediate early genes (IEGs) and longer-term chromatin remodeling around secondary response genes (SRGs). Here, we use high-resolution chromosome-conformation-capture carbon-copy sequencing (5C-seq) to elucidate the extent to which long-range chromatin loops are altered during short- and long-term changes in neural activity. We find that more than 10% of loops surrounding select IEGs, SRGs, and synaptic genes are induced de novo during cortical neuron activation.

The microbiota protects from viral-induced neurologic damage through microglia-intrinsic TLR signaling.

Symbiotic microbes impact the function and development of the central nervous system (CNS); however, little is known about the contribution of the microbiota during viral-induced neurologic damage. We identify that commensals aid in host defense following infection with a neurotropic virus through enhancing microglia function. Germfree mice or animals that receive antibiotics are unable to control viral replication within the brain leading to increased paralysis.

The Neuronal Gene Arc Encodes a Repurposed Retrotransposon Gag Protein that Mediates Intercellular RNA Transfer.

The neuronal gene Arc is essential for long-lasting information storage in the mammalian brain, mediates various forms of synaptic plasticity, and has been implicated in neurodevelopmental disorders. However, little is known about Arc's molecular function and evolutionary origins. Here, we show that Arc self-assembles into virus-like capsids that encapsulate RNA.

Activity-Dependent Arc Expression and Homeostatic Synaptic Plasticity Are Altered in Neurons from a Mouse Model of Angelman Syndrome.

Angelman syndrome (AS) is a neurodevelopmental disorder that results from deletions or mutations in chromosome 15, which usually includes the gene. Ube3A protein is an E3 ubiquitin ligase that ubiquitinates proteins and targets them for degradation. The immediate-early gene Arc, a master regulator of synaptic plasticity, was identified as a putative substrate of Ube3A, but there have been conflicting reports on whether Arc is a bona fide E3 ligase substrate.

Arc restores juvenile plasticity in adult mouse visual cortex.

The molecular basis for the decline in experience-dependent neural plasticity over age remains poorly understood. In visual cortex, the robust plasticity induced in juvenile mice by brief monocular deprivation during the critical period is abrogated by genetic deletion of Arc, an activity-dependent regulator of excitatory synaptic modification. Here, we report that augmenting Arc expression in adult mice prolongs juvenile-like plasticity in visual cortex, as assessed by recordings of ocular dominance (OD) plasticity in vivo.

Deep-brain imaging via epi-fluorescence Computational Cannula Microscopy.

Here we demonstrate widefield (field diameter = 200 μm) fluorescence microscopy and video imaging inside the rodent brain at a depth of 2 mm using a simple surgical glass needle (cannula) of diameter 0.22 mm as the primary optical element. The cannula guides excitation light into the brain and the fluorescence signal out of the brain.

Methamphetamine-induced neurotoxicity disrupts pharmacologically evoked dopamine transients in the dorsomedial and dorsolateral striatum.

Phasic dopamine (DA) signaling, during which burst firing by DA neurons generates short-lived elevations in extracellular DA in terminal fields called DA transients, is implicated in reinforcement learning. Disrupted phasic DA signaling is proposed to link DA depletions and cognitive-behavioral impairment in methamphetamine (METH)-induced neurotoxicity. Here, we further investigated this disruption by assessing effects of METH pretreatment on DA transients elicited by a drug cocktail of raclopride, a D2 DA receptor antagonist, and nomifensine, an inhibitor of the dopamine transporter (DAT).

Changes in neural circuitry regulating response-reversal learning and Arc-mediated consolidation of learning in rats with methamphetamine-induced partial monoamine loss.

Methamphetamine (METH)-induced neurotoxicity results in long-lasting depletions of monoamines and changes in basal ganglia function. We previously reported that rats with METH-induced neurotoxicity no longer engage dorsomedial striatum during a response-reversal learning task, as their performance is insensitive to acute disruption of dorsomedial striatal function by local infusion of an N-methyl-D-aspartate receptor antagonist or an antisense oligonucleotide against the activity-regulated cytoskeleton-associated (Arc) gene. However, METH-pretreated rats perform the task as well as controls.

Phasic-like stimulation of the medial forebrain bundle augments striatal gene expression despite methamphetamine-induced partial dopamine denervation.

Methamphetamine-induced partial dopamine depletions are associated with impaired basal ganglia function, including decreased preprotachykinin mRNA expression and impaired transcriptional activation of activity-regulated, cytoskeleton-associated (Arc) gene in striatum. Recent work implicates deficits in phasic dopamine signaling as a potential mechanism linking methamphetamine-induced dopamine loss to impaired basal ganglia function. This study thus sought to establish a causal link between phasic dopamine transmission and altered basal ganglia function by determining whether the deficits in striatal neuron gene expression could be restored by increasing phasic dopamine release.

Altered learning and Arc-regulated consolidation of learning in striatum by methamphetamine-induced neurotoxicity.

Methamphetamine (METH) causes partial depletion of central monoamine systems and cognitive dysfunction in rats and humans. We have previously shown and now further show that the positive correlation between expression of the immediate-early gene Arc (activity-regulated, cytoskeleton-associated) in the dorsomedial (DM) striatum and learning on a response reversal task is lost in rats with METH-induced striatal dopamine loss, despite normal behavioral performance and unaltered N-methyl-D-aspartate (NMDA) receptor-mediated excitatory post-synaptic currents, suggesting intact excitatory transmission. This discrepancy suggests that METH-pretreated rats may no longer be using the dorsal striatum to solve the reversal task.