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Intellectual disability is a prevalent disorder that remains incurable. Mutations of the X-linked protein PHF6 cause the intellectual disability disorder Börjeson-Forssman-Lehmann syndrome (BFLS). However, the biological role of PHF6 relevant to BFLS pathogenesis has remained unknown. We report that knockdown of PHF6 profoundly impairs neuronal migration in the mouse cerebral cortex in vivo, leading...
Benzodiazepines (BZs) allosterically modulate γ-aminobutyric acid type-A receptors (GABA A Rs) to increase inhibitory synaptic strength. Diazepam binding inhibitor (DBI) protein is a BZ site ligand expressed endogenously in the brain, but functional evidence for BZ-mimicking positive modulatory actions has been elusive. We demonstrate an endogenous potentiation of GABAergic synaptic transmission...
Although communication between neurons is considered a function of the synapse, neurons also release neurotransmitter from their dendrites. We found that dendritic transmitter release coordinates activity across distinct neuronal populations to generate integrative homeostatic responses. We show that activity-dependent vasopressin release from hypothalamic neuroendocrine neurons in the paraventricular...
Neural circuits are shaped by activity-dependent elimination of redundant synapses during postnatal development. In many systems, postsynaptic activity is known to be crucial, but the precise mechanisms remain elusive. Here, we report that the immediate early gene Arc/Arg3.1 mediates elimination of surplus climbing fiber (CF) to Purkinje cell (PC) synapses in the developing cerebellum. CF synapse...
Recent studies have reported the existence of hippocampal “time cells,” neurons that fire at particular moments during periods when behavior and location are relatively constant. However, an alternative explanation of apparent time coding is that hippocampal neurons “path integrate” to encode the distance an animal has traveled. Here, we examined hippocampal neuronal firing patterns as rats ran in...
Previous studies have shown that neurons in area V4 are involved in the processing of shapes of intermediate complexity and are sensitive to curvature. These studies also suggest that curvature-tuned neurons are position invariant. We sought to examine the mechanisms that endow V4 neurons with these properties. Consistent with previous studies, we found that response rank order to the most- and least-preferred...
Studies of resting-state activity in the brain have provoked critical questions about the brain’s functional organization, but the biological basis of this activity is not clear. Specifically, the relationships between interregional correlations in resting-state measures of activity, neuronal functional connectivity and anatomical connectivity are much debated. To investigate these relationships,...
Recent findings have ignited a controversy over whether the hippocampus is critical for visual perception as well as memory. Some studies have shown that hippocampal damage impairs perception of scenes, but others found no evidence for hippocampal involvement. These studies measured perception as a unitary phenomenon, but recent findings indicate that perceptual discriminations can be based on two...
Early stages of visual processing must capture complex, dynamic inputs. While peripheral neurons often implement efficient encoding by exploiting natural stimulus statistics, downstream neurons are specialized to extract behaviorally relevant features. How do these specializations arise? We use two-photon imaging in Drosophila to characterize a first-order interneuron, L2, that provides input to a...
In this issue of Neuron, Wang et al. (2013) demonstrate that spontaneous neural activity measured using functional neuroimaging is strongly related to millisecond-scale neuronal interactions and topographically precise anatomical connections in the primate somatosensory cortex.
Neurotransmitter spillover represents a form of neural transmission not restricted to morphologically defined synaptic connections. Communication between climbing fibers (CFs) and molecular layer interneurons (MLIs) in the cerebellum is mediated exclusively by glutamate spillover. Here, we show how CF stimulation functionally segregates MLIs based on their location relative to glutamate release. Excitation...
Structure and function of presynaptic terminals are critical for the transmission and processing of neuronal signals. Trans-synaptic signaling systems instruct the differentiation and function of presynaptic release sites, but their downstream mediators are only beginning to be understood. Here, we identify the intracellular mSYD1A (mouse Synapse-Defective-1A) as a regulator of presynaptic function...
The ability to visualize endogenous proteins in living neurons provides a powerful means to interrogate neuronal structure and function. Here we generate recombinant antibody-like proteins, termed Fibronectin intrabodies generated with mRNA display (FingRs), that bind endogenous neuronal proteins PSD-95 and Gephyrin with high affinity and that, when fused to GFP, allow excitatory and inhibitory synapses...
In this issue of Neuron, Christian et al. (2013) provide functional evidence for positive endozepines (positive allosteric modulators of GABA A Rs) within the thalamic reticular nucleus. These molecules are encoded by the Dbi gene and modulate thalamocortical oscillations.
The location, size, and number of synapses critically influence the specificity and strength of neural connections. In axons, synaptic vesicle (SV) and active zone (AZ) proteins are transported by molecular motors and accumulate at discrete presynaptic loci. Little is known about the mechanisms coordinating presynaptic protein transport and deposition to achieve proper distribution of synaptic material...
Epigenetic reprogramming of adult human somatic cells to alternative fates, such as the conversion of human skin fibroblasts to induced pluripotency stem cells (iPSC), has enabled the generation of novel cellular models of CNS disorders. Cell reprogramming models appear particularly promising in the context of human neurological disorders of aging such as Alzheimer’s disease (AD), Parkinson’s disease...
In this issue of Neuron, Kraus et al. (2013) show that a population of “time cells” in the hippocampus responds to the passage of time rather than simply reflecting path integration. This study advances our understanding of how time is represented in the hippocampus.
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