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Interneurons in the cerebral cortex regulate cortical functions through the actions of distinct subgroups that express parvalbumin, somatostatin, or calretinin. The genesis of the first two subgroups requires the expression of NKX2.1, which is maintained by SHH signaling during neurogenesis. In this paper, we report that mosaic elimination in the medial ganglionic eminence (MGE) of Smo, a key effector...
Computations in cortical circuits are mediated by synaptic interactions between excitatory and inhibitory neurons, and yet we know little about their activity in awake animals. Here, through single and dual whole-cell recordings combined with two-photon microscopy in the barrel cortex of behaving mice, we directly compare the synaptically driven membrane potential dynamics of inhibitory and excitatory...
The branching of dendrites and axons is a key determinant of neural circuit formation. In this issue of Neuron, Kawabe et al. demonstrate that the ubiquitin ligase Nedd4 promotes the branching of developing dendrites by targeting the small G protein Rap2. In a complementary study, Drinjakovic et al. show that Nedd4 promotes the branching of developing axons by ubiquitinating a different target, the...
In this issue of Neuron, Abraham et al. report a direct connection between inhibitory function and olfactory behavior. Using molecular methods to alter glutamate receptor subunit composition in olfactory bulb granule cells, the authors found a selective modulation in the time required for difficult, but not simple, olfactory discrimination tasks.
Nedd4-1 is a “neuronal precursor cell expressed and developmentally downregulated protein” and among the most abundant E3 ubiquitin ligases in mammalian neurons. In analyses of conventional and conditional Nedd4-1-deficient mice, we found that Nedd4-1 plays a critical role in dendrite formation. Nedd4-1, the serine/threonine kinase TNIK, and Rap2A form a complex that controls Nedd4-1-mediated ubiquitination...
Neurons in visual, somatosensory, and auditory cortex can respond to the termination as well as the onset of a sensory stimulus. In auditory cortex, these off responses may underlie the ability of the auditory system to use sound offsets as cues for perceptual grouping. Off responses have been widely proposed to arise from postinhibitory rebound, but this hypothesis has never been directly tested...
Regulated protein degradation via the ubiquitin-proteasome system (UPS) plays a central role in building synaptic connections, yet little is known about either which specific UPS components are involved or UPS targets in neurons. We report that inhibiting the UPS in developing Xenopus retinal ganglion cells (RGCs) with a dominant-negative ubiquitin mutant decreases terminal branching in the tectum...
Local inhibitory circuits are thought to shape neuronal information processing in the central nervous system, but it remains unclear how specific properties of inhibitory neuronal interactions translate into behavioral performance. In the olfactory bulb, inhibition of mitral/tufted cells via granule cells may contribute to odor discrimination behavior by refining neuronal representations of odors...
Endocannabinoids serve as retrograde messengers that are released by postsynaptic cells to regulate neurotransmitter release from presynaptic boutons. A new study in this issue of Neuron by Tanimura et al. establishes that most endocannabinoid signaling in the brain is a consequence of the calcium-dependent or receptor-driven generation of the retrograde signal 2-arachidonoylglycerol (2-AG) by diacylglycerol...
Endocannabinoids are released from postsynaptic neurons and cause retrograde suppression of synaptic transmission. Anandamide and 2-arachidonoylglycerol (2-AG) are regarded as two major endocannabinoids. To determine to what extent 2-AG contributes to retrograde signaling, we generated and analyzed mutant mice lacking either of the two 2-AG synthesizing enzymes diacylglycerol lipase α (DGLα) and β...
Alterations in sensory processing constitute prominent symptoms of fragile X syndrome; however, little is known about how disrupted synaptic and circuit development in sensory cortex contributes to these deficits. To investigate how the loss of fragile X mental retardation protein (FMRP) impacts the development of cortical synapses, we examined excitatory thalamocortical synapses in somatosensory...
MicroRNAs (miRNAs) are noncoding RNAs that suppress translation of specific mRNAs. The miRNA machinery interacts with fragile X mental retardation protein (FMRP), which functions as translational repressor. We show that miR-125b and miR-132, as well as several other miRNAs, are associated with FMRP in mouse brain. miR-125b and miR-132 had largely opposing effects on dendritic spine morphology and...
High-resolution functional MRI (hr-fMRI) affords unique leverage on the functional properties of human medial temporal lobe (MTL) substructures. We review initial hr-fMRI efforts to delineate (1) encoding and retrieval processes within the hippocampal circuit, (2) hippocampal subfield contributions to pattern separation and pattern completion, and (3) the representational capabilities of distinct...
The predisposition of human beings toward spiritual feeling, thinking, and behaviors is measured by a supposedly stable personality trait called self-transcendence. Although a few neuroimaging studies suggest that neural activation of a large fronto-parieto-temporal network may underpin a variety of spiritual experiences, information on the causative link between such a network and spirituality is...
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