Segregation and rapid turnover of EDEM1 by an autophagy-like mechanism modulates standard ERAD and folding activities

EDEM1 is a crucial regulator of endoplasmic reticulum (ER)-associated degradation (ERAD) that extracts non-native glycopolypeptides from the calnexin chaperone system. Under normal growth conditions, the intralumenal level of EDEM1 must be low to prevent premature interruption of ongoing folding programs. We report that in unstressed cells, EDEM1 is segregated from the bulk ER into LC3-I-coated vesicles and is rapidly degraded. The rapid turnover of EDEM1 is regulated by a novel mechanism that shows similarities but is clearly distinct from macroautophagy. Cells with defective EDEM1 turnover contain unphysiologically high levels of EDEM1, show enhanced ERAD activity and are characterized by impaired capacity to efficiently complete maturation of model glycopolypeptides. We define as ERAD tuning the mechanisms operating in the mammalian ER at steady state to offer kinetic advantage to folding over disposal of unstructured nascent chains by selective and rapid degradation of ERAD regulators.     

Retino-Cortical Mapping Ratio Predicts Columnar and Salt-and-Pepper Organization in Mammalian Visual Cortex

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Arm movements in monkeys: behavior and neurophysiology

Reaching to objects of interest is very common in the behavioral repertoire of primates. Monkeys possess keen binocular vision and make graceful and accurate arm movements. This review focuses on behavioral and neurophysiological aspects of eye-hand coordination in behaving monkeys, including neural coding mechanisms at the single cell level and in neuronal populations. The results of these studies have converged to a common behavioral-neurophysiological ground and provided a springboard for studies of brain mechanisms underlying motor cognitive function.     

Direction selectivity of inhibitory interneurons in mouse barrel cortex differs between interneuron subtypes

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Bicuculline application affects discharge pattern and pulse-duration tuning characteristics of bat inferior collicular neurons

This study examines the contribution of GABAergic inhibition to the discharge pattern and pulse duration tuning characteristics of 101 bat inferior collicular neurons by means of bicuculline application to their recording sites. When stimulated with single pulses, 56 (55%) neurons discharged 1 or 2 impulses (phasic responders), 42 (42%) discharged 3–10 impulses (phasic bursters) and 3 (3%) discharged impulses throughout the stimulus duration (tonic responders). Bicuculline application increased the number of impulses and changed the discharge patterns of 66 neurons. Using 50% difference between maximal and minimal responses as a criterion, the duration tuning characteristics of these neurons can be described as band-pass (20, 20%), long-pass (17, 17%), short-pass (33, 32%), and all-pass (31, 31%). Each band-pass neuron discharged maximally to a specific duration (the best duration) which was at least 50% larger than the neuron's responses to a long-duration pulse and a short-duration pulse. In contrast, each long- or short-pass neuron discharged maximally to a range of long or short duration pulses. Bicuculline application changed the duration tuning characteristics of 65 neurons. Possible mechanisms underlying duration tuning characteristics and the behavioral relevance to bat echolocation are discussed. Accepted: 4 November 1998     

Orientation and direction tuning align with dendritic morphology and spatial connectivity in mouse visual cortex

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Psychophysical evidence of damaged active processing mechanisms in Belgian Waterslager Canaries

Belgian Waterslager canaries (BWC), bred for a distinct low-pitched song, have an inherited high-frequency hearing loss associated with hair cell abnormalities. Hair cells near the abneural edge of the papilla, which receive primarily efferent innervation in normal birds, are among the most severely affected. These cells are thought to support nonlinear active processing in the avian ear, though the mechanisms are poorly understood. Here we present psychophysical evidence that suggests degraded active processing in BWC compared to normal-hearing non-BWC. Critical ratios, psychophysical masking patterns and phase effects on masking by harmonic complexes were measured in BWC and non-BWC using operant conditioning procedures. Critical ratios were much larger in BWC than in non-BWC at high frequencies. Psychophysical tuning curves derived from the masking patterns for BWC were broadened at high frequencies. BWC also showed severely reduced phase effects on masking by harmonic complexes compared to non-BWC. As has been hypothesized previously for hearing-impaired humans, these results are consistent with a loss of active processing mechanisms in BWC.     

Frequency-intensity characteristics of cricket cercal interneurons: broadband units

The bilateral pairs of cercal interneurons 10-2a and 10-3a in the cricket terminal ganglion are supposed to constitute a functional system for measuring the direction of air-borne signals, based on their phase-locked responses and selective directional sensitivity. The purpose of this study was to obtain information on the frequency and intensity characteristics and thus the potential working range of this system. By recording intracellularly from the axons of the interneurons we measured responses for stimuli of varying frequency, intensity, and direction. Typically, the stimulus frequency range examined extended from 5 to 600 Hz, at intensities of 0.03–30 mm s⁻¹ (peak-to-peak air-particle velocity). The results show that interneurons 10-2a and 10-3a preserved their level of activity, response type, and direction tuning in the whole frequency range tested. Stimulus-response cross-correlograms revealed that spike trains were synchronized with stimulus waves at even higher frequencies, at least up to 1000 Hz. At a given air-particle velocity in the range of about 2–2.5 logarithmic units, the spike number responses of the interneurons were nearly constant over a wide frequency range. Directional diagrams appeared to be independent of stimulus frequency, both in orientation and in amplitude. Accepted: 14 October 1998     

Dynamic adoption of anergy by antigen-exhausted CD4+ T cells

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3D pose estimation enables virtual head fixation in freely moving rats

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