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The retina adapts to average light intensity but also to the range of light intensities (contrast). A study by Baccus and Meister, in this issue of Neuron, identifies three ways that ganglion cells and interneurons adapt to high contrast: shorten integration time, reduce gain, and depolarize. Only the depolarization decays, over tens of seconds.
Cyclic nucleotide-gated (CNG) channels play a central role in the conversion of sensory stimuli into electrical signals. CNG channels form heterooligomeric complexes built of A and B subunits. Here, we study the subunit stoichiometry of the native rod CNG channel by chemical crosslinking. The apparent molecular weight (Mw) of each crosslink product was determined by SDS-PAGE, and its composition was...
Recent physiological studies of alert primates have revealed cortical neural correlates of key steps in a perceptual decision-making process. To elucidate synaptic mechanisms of decision making, I investigated a biophysically realistic cortical network model for a visual discrimination experiment. In the model, slow recurrent excitation and feedback inhibition produce attractor dynamics that amplify...
Sensory perception has traditionally been attributed to the activation of sensory cortices. However, by inducing an illusory perception of movement, Naito and colleagues show in this issue of Neuron that the illusory perception of movement is related to activation of primary motor cortex.
To characterize Ca2+-mediated synaptic vesicle fusion, we analyzed Drosophila synaptotagmin I mutants deficient in specific interactions mediated by its two Ca2+ binding C2 domains. In the absence of synaptotagmin I, synchronous release is abolished and a kinetically distinct delayed asynchronous release pathway is uncovered. Synapses containing only the C2A domain of synaptotagmin partially recover...
The visual system adapts to the magnitude of intensity fluctuations, and this process begins in the retina. Following the switch from a low-contrast environment to one of high contrast, ganglion cell sensitivity declines in two distinct phases: a fast change occurs in <0.1 s, and a slow decrease over ∼10 s. To examine where these modulations arise, we recorded intracellularly from every major cell...
Quaking viable (qkv) mice fail to properly compact myelin in their central nervous systems. Although the defect in the qkv mice involves a mutation affecting the expression of the alternatively spliced qk gene products, their roles in myelination are unknown. We show that the QKI RNA binding proteins regulate the nuclear export of MBP mRNAs. Disruption of the QKI nucleocytoplasmic equilibrium in oligodendrocytes...
We demonstrate a noninvasive technique for protein photoinactivation using a transgenically encoded tag. A tetracysteine motif that binds the membrane-permeable fluorescein derivative 4′,5′-bis(1,3,2-dithioarsolan-2-yl)fluorescein (FlAsH) was engineered into synaptotagmin I (Syt I4C). Neuronally expressed Syt I4C rescues the syt I null mutation, can be visualized after FlAsH labeling, and is normally...
The C. elegans polymodal ASH sensory neurons detect mechanical, osmotic, and chemical stimuli and release glutamate to signal avoidance responses. To investigate the mechanisms of this polymodal signaling, we have characterized the role of postsynaptic glutamate receptors in mediating the response to these distinct stimuli. By studying the behavioral and electrophysiological properties of worms defective...
Neuronal activity influences myelination of the brain, but the molecular mechanisms involved are largely unknown. Here, we report that oligodendrocyte progenitor cells (OPCs) express functional adenosine receptors, which are activated in response to action potential firing. Adenosine acts as a potent neuron-glial transmitter to inhibit OPC proliferation, stimulate differentiation, and promote the...
Phototransduction relies on the precise balance of speed and sensitivity to achieve optimal performance. The cyclic nucleotide-gated (CNG) ion channels, with their Ca2+ permeability, high sensitivity to changes in cytosolic cGMP, rapid gating kinetics, and Ca2+-calmodulin modulation, are beautifully optimized for their role in light detection. Many of these specializations come about from the heteromeric...
Neurons in the primary visual cortex (V1) are organized into an orientation map consisting of orientation domains arranged radially around “pinwheel centers” at which the representations of all orientations converge. We have combined optical imaging of intrinsic signals with intracellular recordings to estimate the subthreshold inputs and spike outputs of neurons located near pinwheel centers or in...
We propose that explicit vision advances in reverse hierarchical direction, as shown for perceptual learning. Processing along the feedforward hierarchy of areas, leading to increasingly complex representations, is automatic and implicit, while conscious perception begins at the hierarchy's top, gradually returning downward as needed. Thus, our initial conscious percept—vision at a glance—matches...
The primary motor cortex (MI) is regarded as the site for motor control. Occasional reports that MI neurons react to sensory stimuli have either been ignored or attributed to guidance of voluntary movements. Here, we show that MI activation is necessary for the somatic perception of movement of our limbs. We made use of an illusion: when the wrist tendon of one hand is vibrated, it is perceived as...
Dopamine neurons of the ventral tegmental area (VTA) are critically involved in processing novel and rewarding information, and mediate the addictive properties of many drugs of abuse. Excitatory synapses on these neurons, like those in other brain regions, exhibit long-term depression (LTD). Amphetamine or dopamine block LTD at VTA synapses, indicating that both pathological and local physiological...
Misshapen (Msn) has been proposed to shut down Drosophila photoreceptor (R cell) growth cone motility in response to targeting signals linked by the SH2/SH3 adaptor protein Dock. Here, we show that Bifocal (Bif), a putative cytoskeletal regulator, is a component of the Msn pathway for regulating R cell growth cone targeting. bif displays strong genetic interaction with msn. Phenotypic analysis indicates...
Receptive field properties of visual cortical neurons depend on the spatiotemporal context within which the stimuli are presented. We have examined the temporal context dependence of cortical orientation tuning using dynamic visual stimuli with rapidly changing orientations. We found that tuning to the orientation of the test stimulus depended on a briefly presented preceding stimulus, with the preferred...
Growing evidence suggests that plasma membranes are locally differentiated into microdomains that are important interaction sites for organization of signaling molecules. These signaling microdomains create local conditions that enhance molecular interactions, excluding others, thereby ensuring speed, spatial localization, and specificity of signal transduction. With the special emphasis on InsP3...
The murine genome contains ∼70 protocadherin (Pcdh) genes. Many are expressed in the nervous system, suggesting that Pcdhs may specify neuronal connectivity. Here, we analyze the 22 contiguous genes of the Pcdh-γ cluster. Individual neurons express subsets of Pcdh-γ genes. Pcdh-γ proteins are present in most neurons and associated with, but not confined to, synapses. Early steps in neuronal migration,...
Visual experience before eye-opening is not usually thought to have any developmental significance. Here we show that naturalistic visual stimuli presented through unopened eyelids robustly activate neurons in the ferret dorsal lateral geniculate nucleus. Further, dark-rearing prior to natural eye-opening has striking effects upon geniculate physiology. Receptive field maps after dark-rearing show...
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