bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development of Orientation Preference Maps in Ferret Primary Visual Cortex
Authors: Chapman Barbara , Stryker Michael P. , Bonhoeffer Tobias 
Published: April 2018

The development of orientation preference maps was studied in ferret primary visual cortex using chronic optical imaging of intrinsic signals. The emergence and maturation of the maps were examined over time in single animals. The earliest age at which cortical domains selectively responsive to particular stimulus orientations were observed varied considerably between individuals, from postnatal day 31 to 36. In all cases, the earliest maps seen were low-contrast, with regions of orientation-specific activity that were difficult to distinguish from noise. These early maps matured over a period of several days into the high-contrast, patchy maps typical of adult animals. The structure of the orientation maps was remarkably constant over time. The indistinct features in the earliest maps were always patches of the same sizes and shapes and at the same locations as in the maps obtained in subsequent recording sessions. Details of the more mature maps, including the relative intensities of individual iso-orientation domains, were also constant from one recording session to another over periods of several weeks. The patterning of iso-orientation domains in ferret primary visual cortex thus is established early in development and remains stable over time, unaffected by either normal visual experience or the anatomical rearrangements of geniculocortical afferents into eye-specific domains.
Sensory Organ Generation in the Chick Inner Ear
Authors: Wu Doris K. , Oh Seung-Ha 
Published: April 2018

There are a total of eight sensory organs in the chick inner ear. Each sensory organ has a distinct structure tailored for its function, and its morphology is well characterized. However, the origin of these sensory organs and the lineage relationships among them are largely unknown. In this report, we show that BMP4 (bone morphogenetic protein), a secreted protein of the TGF-β gene family, is the earliest sensory marker identified to date for the chick inner ear. In addition to BMP4, we show that Msx-1 is a sensory marker for the three cristae, the lagena, and macula neglecta. P75NGFR (nerve growth factor receptor) is a marker for the three cristae only. Based on the expression pattern of these three genes—BMP4, Msx-1, and p75NGFR—it is estimated that the first sensory organs to be generated were the superior and posterior cristae at stage 19, followed by the macula sacculi at stage 20, the lateral crista at stage 22, the basilar papilla and lagena at stage 23, the macula utriculi at stage 24, and the macula neglecta at stage 29. The age of generation of each sensory organ as defined by the first appearance of these molecular markers is well in advance of the histological differentiation. In addition, the differential gene expressions in each presumptive sensory organ may contribute to the distinct structure of the mature organ.
μ-Opioid and δ-Opioid Receptors Are Expressed in Brainstem Antinociceptive Circuits: Studies Using Immunocytochemistry and Retrograde Tract-Tracing
Authors: Kalyuzhny Alexander E. , Arvidsson Ulf , Wu Wei , Wessendorf Martin W. 
Published: April 2018

Opioid-produced antinociception in mammals seems to be mediated in part by pathways originating in the periaqueductal gray (PAG) and the rostroventral medulla (RVM), and these pathways may include serotonergic neurons. In the present study, we examined the relationship of the cloned μ- and δ-receptors (MOR1 and DOR1, respectively) to PAG neurons projecting to the RVM, and RVM neurons projecting to the dorsal spinal cord. This was carried out by combining immunocytochemical staining for MOR1, DOR1, and serotonin with fluorescent retrograde tract-tracing. Of 133 retrogradely labeled cells in the RVM, 31% were immunoreactive for MOR1. Of the double-labeled cells, 41% also were immunoreactive for 5HT. Fifty-three percent of retrogradely labeled cells were apposed by DOR1-ir varicosities; 29% of the apposed cells were immunoreactive for 5HT. In the mesencephalon, cells retrogradely labeled from the RVM were usually surrounded by MOR1-ir structures; however, retrogradely labeled cells were never observed to be immunoreactive for MOR1. Similarly, retrogradely labeled cells in the caudal midbrain were seldom, if ever, labeled for DOR1; however, they frequently were apposed by DOR1-ir varicosities. Of 156 retrogradely labeled profiles from three rats, 52 (33%) were apposed by DOR1-ir varicosities. We conclude that both μ- and δ-opioid receptors could be involved in the antinociception mediated by the PAG–RVM–spinal cord circuit. In addition, opioids seem likely to have both direct and indirect effects on spinally projecting RVM cells in general, and on serotonergic RVM cells in particular.
Spinal Cord Terminations of the Medial Wall Motor Areas in Macaque Monkeys
Authors: Dum Richard P. , Strick Peter L. 
Published: April 2018

We used anterograde transport of wheat germ agglutinin-horseradish peroxidase to examine the pattern of spinal termination of efferents from the supplementary motor area (SMA) and the two caudal cingulate motor areas (CMAd and CMAv). Our analysis was limited to cervical segments of the macaque. For comparison, we also examined the pattern of termination of efferents from the primary motor cortex (M1).The SMA, CMAd, CMAv, and M1 all terminate in the ventral horn (lamina IX). Thus, all of these motor areas appear to have direct connections with spinal motoneurons, particularly those innervating muscles of the fingers and wrist. All of the motor areas also terminate in the intermediate zone of the spinal cord (laminae V–VIII). Terminations from the SMA and M1 were densest in three regions: (1) dorsolaterally within laminae V–VII; (2) dorsomedially within lamina VI; and (3) ventromedially within lamina VII and adjacent lamina VIII. In contrast, efferents from the CMAd terminate most densely in the dorsolateral portion of the intermediate zone, whereas those from the CMAv were concentrated in the dorsomedial region. Thus, the CMAd and CMAv may innervate distinct sets of interneurons that project directly to motoneurons, and thereby influence specific aspects of segmental motor control.These results suggest that corticospinal projections from the SMA, CMAd, and CMAv are in many respects similar to those of efferents from M1. Consequently, each of the motor areas on the medial wall has the potential to generate and control movement at the level of the spinal cord and may provide an anatomical substrate for the recovery of motor function that follows damage to M1.
Respiratory Neurons Mediating the Breuer–Hering Reflex Prolongation of Expiration in Rat
Authors: Hayashi Fumiaki , Coles Sharon K. , McCrimmon Donald R. 
Published: April 2018

Afferent input from pulmonary stretch receptors is important in the control of the timing of inspiratory and expiratory phases of the respiratory cycle. The current study was undertaken to identify neurons within a column of respiratory neurons in the ventrolateral medulla (termed the ventral respiratory group, VRG) that, when activated by lung inflation, produce the Breuer–Hering (BH) reflex in which lung inflation causes inspiratory termination and expiratory prolongation. Intracellular recordings of VRG neurons revealed three groups of inspiratory (I) and two groups of expiratory (E) neurons similar to previous descriptions: I-augmenting (I-Aug), I-decrementing (I-Dec), I-plateau (I-All), E-augmenting (E-Aug), and E-decrementing (E-Dec) neurons. Low-intensity, low-frequency stimulation of a vagus nerve elicited paucisynaptic EPSPs in E-Dec, I-Aug, and I-All neurons that could be divided into two groups on the basis of latency (2.8 ± 0.1 msec,n = 10; 4.0 ± 0.1 msec,n = 17). IPSPs were elicited in I-Aug and I-All neurons (4.8 ± 0.1 msec,n = 12). However, only E-Dec neurons were depolarized when the BH reflex was activated by lung inflation (7.5 cm H2O) or mimicked by vagus nerve stimulation (50 Hz). All other neurons were hyperpolarized and ceased firing during BH reflex-mediated expiratory prolongation. A subset of E-Dec neurons (termed E-Decearly) discharged before inspiratory termination and could contribute to inspiratory termination. The findings are consistent with the hypothesis that a group of E-Dec neurons receives a paucisynaptic (probably disynaptic) input from pulmonary afferents and, in turn, inhibits inspiratory neurons, thereby lengthening expiration.
Neural Delays Shape Selectivity to Interaural Intensity Differences in the Lateral Superior Olive
Authors: Park Thomas J. , Grothe Benedikt , Pollak George D. , Schuller Gerd , Koch Ursula 
Published: April 2018

Neurons in the lateral superior olive (LSO) respond selectively to interaural intensity differences (IIDs), one of the chief cues used to localize sounds in space. LSO cells are innervated in a characteristic pattern: they receive an excitatory input from the ipsilateral ear and an inhibitory input from the contralateral ear. Consistent with this pattern, LSO cells generally are excited by sounds that are more intense at the ipsilateral ear and inhibited by sounds that are more intense at the contralateral ear. Despite their relatively homogeneous pattern of innervation, IID selectivity varies substantially from cell to cell, such that selectivities are distributed over the range of IIDs that would be encountered in nature. For some time, researchers have speculated that the relative timing of the excitatory and inhibitory inputs to an LSO cell might shape IID selectivity. To test this hypothesis, we recorded from 50 LSO cells in the free-tailed bat while presenting stimuli that varied in interaural intensity and in interaural time of arrival. The results suggest that, for more than half of the cells, the latency of inhibition was several hundred microseconds longer than the latency of excitation. Increasing the intensity to the inhibitory ear shortened the latency of inhibition and brought the timing of the inputs from the two ears into register. Thus, a neural delay of the inhibition helped to define the IID selectivity of these cells, accounting for a significant part of the variation in selectivity among LSO cells.
Matrix Metalloproteinase-9 (MMP-9) Is Synthesized in Neurons of the Human Hippocampus and Is Capable of Degrading the Amyloid-β Peptide (1–40)
Authors: Backstrom Jon R. , Lim Giselle P. , Cullen Michael J. , Tökés Zoltán A. 
Published: April 2018

We reported earlier that the levels of Ca2+-dependent metalloproteinases are increased in Alzheimer’s disease (AD) specimens, relative to control specimens. Here we show that these enzymes are forms of the matrix metalloproteinase MMP-9 (EC3.4.24.35) and are expressed in the human hippocampus. Affinity-purified antibodies to MMP-9 labeled pyramidal neurons, but not granular neurons or glial cells. MMP-9 mRNA is expressed in pyramidal neurons, as determined with digoxigenin-labeled MMP-9 riboprobes, and the presence of this mRNA is confirmed with reverse transcriptase PCR. The cellular distribution of MMP-9 is altered in AD because 76% of the total 100 kDa enzyme activity is found in the soluble fraction of control specimens, whereas only 51% is detectable in the same fraction from AD specimens. The accumulated 100 kDa enzyme from AD brain is latent and can be converted to an active form with aminophenylmercuric acetate.MMP-9 also is detected in close proximity to extracellular amyloid plaques. Because a major constituent of plaques is the 4 kDa β-amyloid peptide, synthetic Aβ1–40was incubated with activated MMP-9. The enzyme cleaves the peptide at several sites, predominantly at Leu34-Met35within the membrane-spanning domain. These results establish that neurons have the capacity to synthesize MMP-9, which, on activation, may degrade extracellular substrates such as β-amyloid. Because the latent form of MMP-9 accumulates in AD brain, it is hypothesized that the lack of enzyme activation contributes to the accumulation of insoluble β-amyloid peptides in plaques.
Changing Patterns of Expression and Subcellular Localization of TrkB in the Developing Visual System
Authors: Cabelli Robert J. , Allendoerfer Karen L. , Radeke Monte J. , Welcher Andrew A. , Feinstein Stuart C. , Shatz Carla J. 
Published: April 2018

Neurotrophins play important roles in the survival, differentiation, and maintenance of CNS neurons. To begin to investigate specific roles for these factors in the mammalian visual system, we have examined the cellular localization of the neurotrophin receptor trkB within the developing cerebral cortex and thalamus of the ferret using extracellular domain-specific antibodies.At prenatal ages (gestation is 41 d), trkB-immunostained fibers were observed in the internal capsule and as two distinct fascicles within the intermediate zone of the cerebral cortex. The staining of these fiber tracts declined with increasing age, whereas soma and dendrite staining of cortical neurons was first evident in early postnatal life and increased during subsequent development. Staining of subplate neurons [by prenatal day 5 (P5)] was followed by staining of cortical layer 5 neurons (at P10). By P31, trkB immunoreactivity was particularly prominent in layers 3 and 5 but was absent from subplate neurons. Staining included cells, especially pyramidal neurons, in all cortical layers by P45, and this pattern was maintained into adulthood. The optic tract and fibers within the lateral geniculate nucleus (LGN) were also strongly trkB immunoreactive at prenatal ages. Cellular staining of a subset of LGN neurons, those within the C-layers and perigeniculate nucleus, was apparent by P10 and maintained until P45, when the adult pattern of highly trkB-immunoreactive neurons in all layers of the LGN first appeared.The pattern of trkB immunoreactivity suggests that specific subsets of cortical and thalamic neurons may respond to neurotrophins such as brain-derived neurotrophic factor and/or NT-4/5 at discrete developmental times and locations. The appearance of trkB on axon fibers early in development and then on cell bodies and dendritic processes later is consistent with roles for both long-range and local, including autocrine and/or paracrine, delivery of neurotrophins in cell survival and maturation.
5HT1BReceptor Agonists Inhibit Light-Induced Phase Shifts of Behavioral Circadian Rhythms and Expression of the Immediate–Early Genec-fosin the Suprachiasmatic Nucleus
Authors: Pickard Gary E. , Weber E. Todd , Scott Paul A. , Riberdy Anne F. , Rea Michael A. 
Published: April 2018

The suprachiasmatic nucleus (SCN) is a circadian oscillator and a critical component of the mammalian circadian system. It receives afferents from the retina and the mesencephalic raphe. Retinal afferents mediate photic entrainment of the SCN, whereas the serotonergic afferents originating from the midbrain modulate photic responses in the SCN; however, the serotonin (5HT) receptor subtypes in the SCN responsible for these modulatory effects are not well characterized. In this study, we tested the hypothesis that 5HT1Breceptors are located presynaptically on retinal axon terminals in the SCN and that activation of these receptors inhibits retinal input.The 5HT1Breceptor agonists TFMPP and CGS 12066A, administered systemically, inhibited light-induced phase shifts of the circadian activity rhythm in a dose-dependent manner at phase delay and phase advance time points. This inhibition was not affected by previous systemic application of either the selective 5HT1Areceptor antagonist (+)WAY 100135 or by the 5HT2receptor antagonist mesulergine, whereas pretreatment with the nonselective 5HT1antagonist methiothepin significantly attenuated the effect of TFMPP. TFMPP also produced a dose-dependent reduction in light-stimulated Fos expression in the SCN, although a small subset of cells in the dorsolateral aspect of the caudal SCN were TFMPP-insensitive. TFMPP (1 mm) infused into the SCN produced complete inhibition of light-induced phase advances. Finally, bilateral orbital enucleation reduced the density of SCN 5HT1Breceptors as determined using [125I]-iodocyanopindolol to define 5HT1Bbinding sites. These results are consistent with the interpretation that 5HT1Breceptors are localized presynaptically on retinal terminals in the SCN and that activation of these receptors by 5HT1Bagonists inhibits retinohypothalamic input.
Calcium-Containing Organelles Display Unique Reactivity to Chemical Stimulation in Cultured Hippocampal Neurons
Authors: Korkotian Eduard , Segal Menahem 
Published: April 2018

Cultured rat hippocampal neurons grown on glass coverslips for 1–3 weeks were loaded with the calcium-sensitive fluorescent dye Fluo-3 and viewed with a confocal laser scanning microscope. Large pyramidal-shaped neurons were found to contain dye-accumulating organelles in their somata, primarily around nuclei and near the base of their primary dendrites. These organelles varied in size and increased in density over weeks in culture, and were not colocalized with the endoplasmic reticulum or with mitochondria. The Fluo-3 fluorescence in these calcium-containing organelles (CCOs) was transiently quenched by exposure to Mn2+, indicating that the dye is a genuine [Ca2+] reporter and is not just a site of accumulating Fluo-3 dye. Recovery of fluorescence in the CCOs after washout of Mn2+involved activation of a thapsigargin-sensitive process.CCOs responded to stimuli that evoke a rise of cytosolic [Ca2+] ([Ca]i) in a unique manner; perfusion of caffeine caused a prolonged rise of [Ca] in the CCOs ([Ca]C), whereas it caused only a transient rise of [Ca]i. Pulse application of caffeine also caused a faster effect on [Ca]Cthan on [Ca]i. Glutamate caused a transient rise of both [Ca]iand [Ca]C, followed by a prolonged fall of only [Ca]Cto below rest level. This fall was blocked by preincubation with thapsigargin. Ryanodine blocked the cytosolic effects of caffeine but not its effect on [C]C.A clear distinction between CCOs and the known calcium stores was seen in digitonin-permeabilized cells; in these, remaining Fluo-3 reported changes in store calcium, i.e., caffeine caused a reduction in Fluo-3 fluorescence in permeabilized cells, whereas it still caused an increase in [Ca]C. A possible role of CCOs in regulation of release of calcium from ryanodine-sensitive stores was indicated by the observation that CCO-containing cells exhibited a larger and faster response to caffeine than cells that did not have them. We propose that CCOs constitute a unique functional compartment involved in release of calcium from calcium-sensitive stores.
Spatially Selective Auditory Responses in the Superior Colliculus of the Echolocating Bat
Authors: Valentine Doreen E. , Moss Cynthia F. 
Published: April 2018

When a bat approaches a target, it continuously modifies its echolocation sounds and relies on incoming echo information to shape the characteristics of its subsequent sonar cries. In addition, acoustic information about the azimuth and elevation of a sonar target elicits orienting movements of the head and pinnae toward the sound source. This requires a common sensorimotor interface, where echo information is used to guide motor behaviors.Using single-unit neurophysiological methods and free-field auditory stimulation, we present data on biologically relevant specializations in the superior colliculus (SC) of the bat for orientation by sonar. In the bat’s SC, two classes of spatially tuned neurons are distinguished by their sensitivity to echoes. One population shows facilitated, delay-tuned responses to pairs of sounds, simulating sonar emissions and echoes. Delay tuning, related to encoding target range, may play a role in guiding motor responses in echolocation, because the bat adjusts its emissions with changes in target distance. The delay-facilitated response depends on the direction of stimulation and on the temporal relationship between the simulated emission and echo in the sound pair, suggesting that this class of neurons represents the location of a target in three dimensions. A second population encodes the target in two dimensions, azimuth and elevation, and does not show a facilitated response to echoes delivered from any locus. Encoding of azimuth and elevation may be important for directing head aim, and this class may function in transforming auditory spatial information into signals used to guide acoustic orientation.
Representation of Accurate Temporal Information in the Electrosensory System of the African Electric Fish,Gymnarchus niloticus
Authors: Guo Yuan-Xing , Kawasaki Masashi 
Published: April 2018

Differential-phase-sensitive neurons in the electrosensory lateral line lobe (ELL) of the African electric fish,Gymnarchus niloticus,are sensitive to time disparities on the order of microseconds between afferent action potentials. These action potentials fire in a phase-locked manner in response to the animal’s own wave-type electric organ discharges (EODs) (Kawasaki and Guo, 1996). The time disparity is one of the essential cues for an electrical behavior, the jamming avoidance response (JAR). To gain an insight into the accurate temporal processing in the ELL, firing time accuracy and dynamic response properties of action potentials of the phase-locked neurons (PLNs) in the ELL were examined. The temporal accuracy of the entire neuronal circuit for the JAR was also measured using behavioral responses.Standard deviation of firing times of PLNs’ action potentials was ∼6 μsec. The PLNs represent zerocrossing times of each stimulus cycle with this accuracy even when stimulus phase was modulated at high frequencies (∼50 Hz). Distinct JAR occurred when time disparity was diminished below 1 μsec, and a marginal JAR could still be detected with a time disparity of 100 nsec. Standard deviation of the firing times of EODs was approximately several hundred nanoseconds. This stability of the EOD, however, was demonstrated to be unnecessary for the JAR. JARs occurred even when a large artificial jitter (∼60 μsec) was introduced to a stimulus that mimicked fish’s own EOD and the time disparity for JAR was diminished to 1 μsec. This immunity of JAR to the EOD jitter is explained by the insensitivity of the differential-phase-sensitive neurons in the ELL to a common phase modulation.The JAR of the South American electric fish,Eigenmannia, also occurs in response to stimuli that generate comparably small phase differences (Rose and Heiligenberg, 1985b; Carr et al., 1986a). The present study revealed that the independently evolvedEigenmanniaandGymnarchusexhibit a comparative level of remarkable temporal accuracy.