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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...
Fear is a graded central motive state ranging from mild to intense. As threat intensity increases, fear transitions from discriminative to generalized. The circuit mechanisms that process threats of different intensity are not well resolved. Here, we isolate a unique population of locally projecting neurons in the central nucleus of the amygdala (CeA) that produce the neuropeptide corticotropin-releasing...
The molecular composition of the postsynaptic membrane is sculpted by synaptic activity. During synaptic plasticity at excitatory synapses, numerous structural, signaling, and receptor molecules concentrate at the postsynaptic density (PSD) to regulate synaptic strength. We developed an approach that uses light to tune the abundance of specific molecules in the PSD. We used this approach to investigate...
AMPA receptors (AMPARs) are tetrameric ion channels that together with other ionotropic glutamate receptors (iGluRs), the NMDA and kainate receptors, mediate a majority of excitatory neurotransmission in the central nervous system. Whereas NMDA receptors gate channels with slow kinetics, responsible primarily for generating long-term synaptic potentiation and depression, AMPARs are the main fast transduction...
Lattice-like structures known as perineuronal nets (PNNs) are key components of the extracellular matrix (ECM). Once fully crystallized by adulthood, they are largely stable throughout life. Contrary to previous reports that PNNs inhibit processes involving plasticity, here we report that the dynamic regulation of PNN expression in the adult auditory cortex is vital for fear learning and consolidation...
Sensory processing must be sensitive enough to encode faint signals near the noise floor but selective enough to differentiate between similar stimuli. Here we describe a layer 6 corticothalamic (L6 CT) circuit in the mouse auditory forebrain that alternately biases sound processing toward hypersensitivity and improved behavioral sound detection or dampened excitability and enhanced sound discrimination...
Synaptic plasticity (e.g., long-term potentiation [LTP]) is considered the cellular correlate of learning. Recent optogenetic studies on memory engram formation assign a critical role in learning to suprathreshold activation of neurons and their integration into active engrams (“engram cells”). Here we review evidence that ensemble integration may result from LTP but also from cell-autonomous changes...
Perceptual decisions require the transformation of raw sensory inputs into cortical representations suitable for stimulus discrimination. One of the best-known examples of this transformation involves the middle temporal area (MT) of the primate visual cortex. Area MT provides a robust representation of stimulus motion, and previous work has shown that it contributes causally to performance on motion...
Activity-dependent neuronal plasticity is a fundamental mechanism through which the nervous system adapts to sensory experience. Several lines of evidence suggest that parvalbumin (PV+) interneurons are essential in this process, but the molecular mechanisms underlying the influence of experience on interneuron plasticity remain poorly understood. Perineuronal nets (PNNs) enwrapping PV+ cells are...
How experiences during development cause long-lasting changes in sensory circuits and affect behavior in mature animals are poorly understood. Here we establish a novel system for mechanistic analysis of the plasticity of developing neural circuits by showing that sensory experience during development alters nociceptive behavior and circuit physiology in Drosophila larvae. Despite the convergence...
Munc13 catalyzes the transit of syntaxin from a closed complex with Munc18 into the ternary SNARE complex. Here we report a new function of Munc13, independent of Munc18: it promotes the proper syntaxin/synaptobrevin subconfiguration during assembly of the ternary SNARE complex. In cooperation with Munc18, Munc13 additionally ensures the proper syntaxin/SNAP-25 subconfiguration. In a reconstituted...
The impact of dentate mossy cells on hippocampal activity remained uncertain despite a long history of investigation. In this issue of Neuron, Hashimotodani et al. (2017) discover a presynaptically expressed form of long-term potentiation at mossy cell outputs, shedding light on their mysterious function.
The motor symptoms of Parkinson’s disease (PD) are linked to abnormally correlated and coherent activity in the cortex and subthalamic nucleus (STN). However, in parkinsonian mice we found that cortico-STN transmission strength had diminished by 50%–75% through loss of axo-dendritic and axo-spinous synapses, was incapable of long-term potentiation, and less effectively patterned STN activity. Optogenetic,...
The mammalian target of rapamycin complex 1 (mTORC1), a transducer of local dendritic translation, participates in learning and memory processes as well as in mechanisms underlying alcohol-drinking behaviors. Using an unbiased RNA-seq approach, we identified Prosapip1 as a novel downstream target of mTORC1 whose translation and consequent synaptic protein expression are increased in the nucleus accumbens...
Schwann cell dedifferentiation from a myelinating to a progenitor-like cell underlies the remarkable ability of peripheral nerves to regenerate following injury. However, the molecular identity of the differentiated and dedifferentiated states in vivo has been elusive. Here, we profiled Schwann cells acutely purified from intact nerves and from the wound and distal regions of severed nerves. Our analysis...
New neurons appear only in a few regions of the adult mammalian brain and become integrated into existing circuits. Little is known about the functional development of individual neurons in vivo. We examined the functional life history of adult-born granule cells (abGCs) in the olfactory bulb using multiphoton imaging in awake and anesthetized mice. We found that abGCs can become responsive to odorants...
The study of brain plasticity has tended to focus on the synapse, where well-described activity-dependent mechanisms are known to play a key role in learning and memory. However, it is becoming increasingly clear that plasticity occurs beyond the synapse. This review focuses on the emerging concept of white matter plasticity. For example, there is growing evidence, both from animal studies and from...
Preservation of a balance between synaptic excitation and inhibition is critical for normal brain function. A number of homeostatic cellular mechanisms have been suggested to play a role in maintaining this balance, including long-term plasticity of GABAergic inhibitory synapses. Many previous studies have demonstrated a coupling of postsynaptic spiking with modification of perisomatic inhibition...
In vertebrates and invertebrates, neurons and glia are generated in a stereotyped manner from neural stem cells, but the purpose of invariant lineages is not understood. We show that two stem cells that produce leg motor neurons in Drosophila also generate neuropil glia, which wrap and send processes into the neuropil where motor neuron dendrites arborize. The development of the neuropil glia and...
Migraine is an extremely common but poorly understood nervous system disorder. We conceptualize migraine as a disorder of sensory network gain and plasticity, and we propose that this framing makes it amenable to the tools of current systems neuroscience.
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