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The capacity for declarative memory depends on the hippocampal region and adjacent cortex within the medial temporal lobe. One of the most widely studied examples of declarative memory is the capacity to recognize recently encountered material as familiar, but uncertainty remains about whether intact recognition memory depends on the hippocampal region itself and, if so, what the nature of the hippocampal...
Drosophila sensory neurons form distinctive terminal branch patterns in the developing neuropile of the embryonic central nervous system. In this paper we make a genetic analysis of factors regulating arbor position. We show that mediolateral position is determined in a binary fashion by expression (chordotonal neurons) or nonexpression (multidendritic neurons) of the Robo3 receptor for the midline...
A key question in developmental neurobiology is how the diversity of cell types that make up the mature nervous system are generated from a common set of progenitor cells. Drosophila genes governing temporal cell fate determination and asymmetric cell divisions involving numb may represent evolutionarily conserved mechanisms for regulating cell fate diversification in the developing nervous system.
The shal gene encodes the transient potassium current (IA) in neurons of the lobster stomatogastric ganglion. Overexpression of Shal by RNA injection into neurons produces a large increase in IA, but surprisingly little change in the neuron's firing properties. Accompanying the increase in IA is a dramatic and linearly correlated increase in the hyperpolarization-activated inward current (Ih). The...
Netrins promote axon outgrowth and turning through DCC/UNC-40 receptors. To characterize Netrin signaling, we generated a gain-of-function UNC-40 molecule, MYR::UNC-40. MYR::UNC-40 causes axon guidance defects, excess axon branching, and excessive axon and cell body outgrowth. These defects are suppressed by loss-of-function mutations in ced-10 (a Rac GTPase), unc-34 (an Enabled homolog), and unc-115...
Diverse cell types and parallel pathways are characteristic of the vertebrate nervous system, yet it remains a challenge to define the basic components of most neural structures. We describe a process termed retrograde photodynamics that allowed us to rapidly make the link between morphology, physiology, and connectivity for ganglion cells in the macaque retina that project to the lateral geniculate...
The fine tuning of synaptic circuits often requires an activity-dependent phase in which appropriate connections are strengthened and inappropriate connections are eliminated. In this issue of Neuron, Walsh and Lichtman propose a novel “synaptic takeover” mechanism for synapse elimination at the vertebrate NMJ, where withdrawal of one axon is accompanied by expansion of a competing axon into the newly...
Here we describe a novel mechanism for plasma membrane insertion of the delta opioid receptor (DOR). In small dorsal root ganglion neurons, only low levels of DORs are present on the cell surface, in contrast to high levels of intracellular DORs mainly associated with vesicles containing calcitonin gene-related peptide (CGRP). Activation of surface DORs caused Ca2+ release from IP3-sensitive stores...
Following a recent report that monkey prefrontal cortex contains cells that represent number concepts, Nieder and Miller investigated the scale used to code numbers. In this issue of Neuron, they report that prefrontal cells use the same scale (Weber's Law) used by sensory neurons to code stimulus intensity, suggesting how abstract cognitive operations may arise from simpler building blocks that humans...
Using a simplified preparation of the Aplysia siphon-withdrawal reflex, we previously found that associative plasticity at synapses between sensory neurons and motor neurons contributes importantly to classical conditioning of the reflex. We have now tested the roles in that plasticity of two associative cellular mechanisms: activity-dependent enhancement of presynaptic facilitation and postsynaptically...
A novel gene for Parkinson's disease (PD), DJ-1, has been identified that encodes a multifunctional product with several known protein-protein interactions and effects on gene expression. Here, I outline how it is possible to construct hypotheses that place DJ-1 in different relationships to the other known PD genes, α-synuclein and parkin. The identification of multiple genetic causes will provide...
Sr2+ triggers neurotransmitter release similar to Ca2+, but less efficiently. We now show that in synaptotagmin 1 knockout mice, the fast component of both Ca2+- and Sr2+-induced release is selectively impaired, suggesting that both cations partly act by binding to synaptotagmin 1. Both the C2A and the C2B domain of synaptotagmin 1 bind Ca2+ in phospholipid complexes, but only the C2B domain forms...
Whether cognitive representations are better conceived as language-based, symbolic representations or perceptually related, analog representations is a subject of debate. If cognitive processes parallel perceptual processes, then fundamental psychophysical laws should hold for each. To test this, we analyzed both behavioral and neuronal representations of numerosity in the prefrontal cortex of rhesus...
Site-specific electrostatic measurements have been limited to soluble proteins purified for in vitro spectroscopic characterization or proteins of known structure; however, comparable measurements have not been made for functional membrane bound proteins. Here, using an electrochromic fluorophore, we describe a method to monitor localized electric field changes in a voltage-gated potassium channel...
We utilized the Cre-LoxP system to establish erbB2 conditional mutant mice in order to investigate the role of erbB2 in postnatal development of the enteric nervous system. The erbB2/nestin-Cre conditional mutants exhibit retarded growth, distended colons, and premature death, resembling human Hirschsprung's disease. Enteric neurons and glia are present at birth in the colon of erbB2/nestin-Cre mutants;...
How do neurons maintain stable intrinsic properties over long periods of time as the channels that govern excitability turn over in the membrane? In this issue of Neuron, MacLean et al. argue that homeostatic regulation of intrinsic activity can occur by an activity-independent mechanism.
The existence of a “critical period” for language acquisition is controversial. Bilingual subjects with variable age of acquisition (AOA) and proficiency level (PL) constitute a suitable model to study this issue. We used functional magnetic resonance imaging to investigate the effects of AOA and PL on neural correlates of grammatical and semantic judgments in Italian-German bilinguals who learned...
During development, competition between axons causes permanent removal of synaptic connections, but the dynamics have not been directly observed. Using transgenic mice that express two spectral variants of fluorescent proteins in motor axons, we imaged competing axons at developing neuromuscular junctions in vivo. Typically, one axon withdrew progressively from postsynaptic sites and the competing...
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