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On axonal surfaces that flank the node of Ranvier and in overlying glial paranodal loops, proteins are arranged within circumscribed microdomains that defy explanation by conventional biosynthetic mechanisms. We postulate that the constraint of proteins to these loci is accomplished in part by discriminative membrane-embedded molecular sieves and diffusion barriers, which serve to organize and redistribute...
The role of mPer1 and mPer2 in regulating circadian rhythms was assessed by disrupting these genes. Mice homozygous for the targeted allele of either mPer1 or mPer2 had severely disrupted locomotor activity rhythms during extended exposure to constant darkness. Clock gene RNA rhythms were blunted in the suprachiasmatic nucleus of mPer2 mutant mice, but not of mPER1-deficient mice. Peak mPER and mCRY1...
Locust antennal lobe (AL) projection neurons (PNs) respond to olfactory stimuli with sequences of depolarizing and hyperpolarizing epochs, each lasting hundreds of milliseconds. A computer simulation of an AL network was used to test the hypothesis that slow inhibitory connections between local neurons (LNs) and PNs are responsible for temporal patterning. Activation of slow inhibitory receptors on...
Synaptic inhibition by GABA A and glycine receptors, which are ligand-gated anion channels, depends on the electrochemical potential for chloride. Several potassium-chloride cotransporters can lower the intracellular chloride concentration [Cl − ] i , including the neuronal isoform KCC2. We show that KCC2 knockout mice died immediately after birth due to severe motor deficits...
Neural responses accompanying anticipation and experience of monetary gains and losses were monitored by functional magnetic resonance imaging. Trials comprised an initial “prospect” (expectancy) phase, when a set of three monetary amounts was displayed, and a subsequent “outcome” phase, when one of these amounts was awarded. Hemodynamic responses in the sublenticular extended amygdala (SLEA) and...
The hypothesis that ventral/anterior left inferior frontal gyrus (LIFG) subserves semantic processing and dorsal/posterior LIFG subserves phonological processing was tested by determining the pattern of functional connectivity of these regions with regions in left occipital and temporal cortex during the processing of words and word-like stimuli. In accordance with the hypothesis, we found strong...
Rapid nerve impulse conduction depends on specialized membrane domains in myelinated nerve, the node of Ranvier, the paranode, and the myelinated internodal region. We report that GPI-linked contactin enables the formation of the paranodal septate-like axo-glial junctions in myelinated peripheral nerve. Contactin clusters at the paranodal axolemma during Schwann cell myelination. Ablation of contactin...
Islet-2 is a LIM/homeodomain-type transcription factor of the Islet-1 family expressed in embryonic zebrafish. Two Islet-2 molecules bind to the LIM domain binding protein (Ldb) dimers. Overexpression of the LIM domains of Islet-2 or the LIM-interacting domain of Ldb proteins prevented binding of Islet-2 to Ldb proteins in vitro and caused similar in vivo defects in positioning, peripheral axonal...
Using visual behavioral screens in Drosophila, we identified multiple alleles of N-cadherin. Removal of N-cadherin selectively from photoreceptor neurons (R cells) causes deficits in specific visual behaviors that correlate with disruptions in R cell connectivity. These defects include disruptions in the pattern of neuronal connections made by all three classes of R cells (R1–R6, R7, and R8). N-cadherin...
The patterning of skeletal muscle is thought to depend upon signals provided by motor neurons. We show that AChR gene expression and AChR clusters are concentrated in the central region of embryonic skeletal muscle in the absence of innervation. Neurally derived Agrin is dispensable for this early phase of AChR expression, but MuSK, a receptor tyrosine kinase activated by Agrin, is required to establish...
Synaptotagmins I and II are Ca 2+ binding proteins of synaptic vesicles essential for fast Ca 2+ -triggered neurotransmitter release. However, central synapses and neuroendocrine cells lacking these synaptotagmins still exhibit Ca 2+ -evoked exocytosis. We now propose that synaptotagmin VII functions as a plasma membrane Ca 2+ sensor in synaptic exocytosis complementary...
Brain functions are based on the dynamic interaction of excitatory and inhibitory inputs. Spillover of glutamate from excitatory synapses may diffuse to and modulate nearby inhibitory synapses. By recording unitary inhibitory postsynaptic currents (uIPSCs) from cell pairs in CA1 of the hippocampus, we demonstrated that low concentrations of Kainate receptor (KAR) agonists increased the success rate...
Mammalian photoreceptors are hyperpolarized by a light stimulus and are commonly thought to be nonspiking neurons. We used the whole-cell patch-clamp technique on surgically excised human retina to examine whether human photoreceptors can elicit action potentials. We discovered that human rod photoreceptors express voltage-gated Na + channels, and generate Na + action potentials, in...
Two manipulations of a visual search task were used to test the hypothesis that the discrimination of a target from distractors by visually responsive neurons in the frontal eye field (FEF) marks the outcome and conclusion of visual processing instead of saccade preparation. First, search efficiency was reduced by increasing the similarity of the distractors to the target. Second, response interference...
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