bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reduced Activity of Hypothalamic Corticotropin-Releasing Hormone Neurons in Transgenic Mice with Impaired Glucocorticoid Receptor Function
Authors: Dijkstra Ivar , Tilders Fred J. H. , Aguilera Greti , Kiss Alexander , Rabadan-Diehl Cristina , Barden Nicholas , Karanth Sharada , Holsboer Florian , Reul Johannes M. H. M. 
Published: April 2018

Loss of central glucocorticoid receptor (GR) function is thought to be involved in the development of neuroendocrine and psychiatric disorders associated with corticotropin-releasing hormone (CRH) hyperactivity. The possible causal relationship between defective GR function and altered activity of CRH neurons was studied in transgenic mice (TG) expressing antisense RNA against GR. Immunocytochemical studies showed significant reductions in CRH immunoreactive neurons in the paraventricular nucleus (PVN) and in CRH and vasopressin (AVP) stores in the external zone of the median eminence. Concomitantly, stimulus-evoked CRH secretion from mediobasal hypothalami of TG micein vitrowas reduced significantly. However, CRH mRNA levels in the PVN of TG mice were marginally lower than those in wild-type (WT) mice.125I-CRH binding autoradiography revealed no differences between WT and TG animals in any of the brain regions that were studied. Basal plasma corticosterone (cort) levels and125I-CRH binding, CRH-R1mRNA, POMC mRNA, and POMC hnRNA levels in the anterior pituitary gland were similar in WT and TG mice. Intraperitoneal injection of interleukin-1β (IL-1β) increased plasma cort levels, CRH mRNA in the PVN, and anterior pituitary POMC hnRNA similarly in WT and TG mice. The injection of saline significantly reduced anterior pituitary CRH-R1mRNA levels in WT mice, but not in TG mice, whereas IL-1β produced a decrease in these mRNA levels in both strains.The data show that long-term GR dysfunction can be associated with reduced activity of CRH neurons in the PVN and decreased sensitivity of pituitary CRH-R1mRNA to stimulus-induced downregulation. Moreover, the hypothalamic changes observed in this model suggest that impaired GR function, at least if present since early embryonic life, does not necessarily result in CRH hyperexpression characteristics of disorders such as major depression.
Immunohistochemical and Cytochemical Localization of the Somatostatin Receptor Subtype sst1in the Somatostatinergic Parvocellular Neuronal System of the Rat Hypothalamus
Authors: Helboe Lone , Stidsen Carsten E. , Møller Morten 
Published: April 2018

Somatostatin is known to mediate its actions through five G-protein-coupled receptors (sst1–sst5). We have studied the expression of the sst1receptor in the rat hypothalamus by using a subtype-specific antiserum. In Western blotting, the antiserum reacted specifically with a band with an apparent molecular weight of 80,000 in membranes prepared from hypothalamic tissue.The localization of the sst1receptor was investigated by immunohistochemistry in hypothalamus sections. Additionally, an immunofluorescent double-labeling was performed for the sst1receptor and somatostatin. Light microscopy revealed that the sst1receptor is located in perikarya and nerve fibers in the rostral periventricular area surrounding the third ventricle as well as in nerve fibers projecting from the perikarya to the external layer of the median eminence. In these neuronal structures, sst1immunoreactivity was found to be colocalized with somatostatin. Furthermore, the location of sst1receptors was studied by immunoelectron microscopy in the median eminence. In the external layer, receptor immunoreactivity was confined to nerve terminals. Immunoreactive nerve terminals were seen to make synapse-like junctions with other both stained and unstained nerve terminals. Thus, the sst1receptor is present in the classic somatostatinergic hypothalamic parvocellular system inhibiting hormone secretion from the anterior pituitary gland. These findings indicate that the sst1receptor may act as an autoreceptor and inhibit the release of somatostatin from periventricular neurons projecting to the median eminence.
The Role of the First Postmitotic Cortical Cells in the Development of Thalamocortical Innervation in theReelerMouse
Authors: Molnár Zoltán , Adams Richard , Goffinet AndréM. , Blakemore Colin 
Published: April 2018

In the mutant mousereeler, the tangential distribution of thalamocortical fibers is essentially normal, even though neurons of the cortical plate accumulate below the entire early-born preplate population (Caviness et al., 1988). This seems incompatible with the hypothesis that cells of the subplate (the lower component of the preplate in normal mammals) form an axonal scaffold that guides thalamic fibers and act as temporary targets for them (Blakemore and Molnár, 1990, Shatz et al., 1990).We used carbocyanine dyes to trace projections in wild-type andreelermice between embryonic day 13 and postnatal day 3. Preplate formation and early extension of corticofugal fibers to form a topographic array are indistinguishable in the two phenotypes. So too are the emergence of thalamic axons in topographic order through the primitive internal capsule, their meeting with preplate axons, and their distribution over the preplate scaffold. Distinctive differences appear after the cortical plate begins to accumulate below the preplate ofreeler, causing the preplate axons to form oblique fascicles, running through the cortical plate. Thalamic axons then pass through the plate within the same fascicles and accumulate in the “superplate” layer for ∼2–3 d, before defasciculating and plunging down to terminate deep in the cortical plate, creating the curious “looping” pattern seen in the adult. Thus, thalamocortical innervation inreelerfollows the same algorithm of development but in relation to the misplaced population of early-born neurons. Far from challenging the theory that preplate fibers guide thalamic axons,reelerprovides strong evidence for it.
Short-Term Memory for Reaching to Visual Targets: Psychophysical Evidence for Body-Centered Reference Frames
Authors: McIntyre J. , Stratta F. , Lacquaniti F. 
Published: April 2018

Pointing to a remembered visual target involves the transformation of visual information into an appropriate motor output, with a passage through short-term memory storage. In an attempt to identify the reference frames used to represent the target position during the memory period, we measured errors in pointing to remembered three-dimensional (3D) targets.Subjects pointed after a fixed delay to remembered targets distributed within a 22 mm radius volume. Conditions varied in terms of lighting (dim light or total darkness), delay duration (0.5, 5.0, and 8.0 sec), effector hand (left or right), and workspace location. Pointing errors were quantified by 3D constant and variable errors and by a novel measure of local distortion in the mapping from target to endpoint positions.The orientation of variable errors differed significantly between light and dark conditions. Increasing the memory delay in darkness evoked a reorientation of variable errors, whereas in the light, the viewer-centered variability changed only in magnitude. Local distortion measurements revealed an anisotropic contraction of endpoint positions toward an “average” response along an axis that points between the eyes and the effector arm. This local contraction was present in both lighting conditions. The magnitude of the contraction remained constant for the two memory delays in the light but increased significantly for the longer delays in darkness. These data argue for the separate storage of distance and direction information within short-term memory, in a reference frame tied to the eyes and the effector arm.
Localization of Myosin-Iβ near Both Ends of Tip Links in Frog Saccular Hair Cells
Authors: Garcı́a Jesús A. , Yee Ann G. , Gillespie Peter G. , Corey David P. 
Published: April 2018

Current evidence suggests that the adaptation motor of mechanoelectrical transduction in vertebrate hair cells is myosin-Iβ. Previously, confocal and electron microscopy of bullfrog saccular hair cells using an anti-myosin-Iβ antibody labeled the tips of stereocilia. We have now done quantitative immunoelectron microscopy to test whether myosin-Iβ is enriched at or near the side plaques of tip links, the proposed sites of adaptation, using hair bundles that were serially sectioned parallel to the macular surface. The highest particle density occurred at stereocilia bases, close to the cuticular plate. Also, stereocilia of differing lengths had approximately the same number of total particles, suggesting equal targeting of myosin-Iβ to all stereocilia. Finally, particles tended to clump in clusters of two to five particles in the distal two-thirds of stereocilia, suggesting a tendency for self-assembly of myosin-Iβ.As expected from fluorescence microscopy, particle density was high in the distal 1 μm of stereocilia. If myosin-Iβ is the adaptation motor, a difference should exist in particle density between regions containing the side plaque and those excluding it. Averaging of particle distributions revealed two regions with approximately twice the average density: at the upper ends of tip links in a 700-nm-long region centered ∼100 nm above the side plaque, and at the lower ends of tip links within the tip plaques. Controls demonstrated no such increase. The shortest stereocilia, which lack side plaques, showed no concentration rise on their sides. Thus, the specific localization of myosin-Iβ at both ends of tip links supports its role as the adaptation motor.
Developmental Regulation of Apoptosis in Dorsal Root Ganglion Neurons
Authors: Vogelbaum Michael A. , Tong Jianxin X. , Rich Keith M. 
Published: April 2018

The survival of dorsal root ganglion (DRG) neurons, bothin vivoandin vitro, is dependent on the availability of nerve growth factor (NGF) for a transient period early in development after which these neurons become independent of NGF for survival. The precise molecular mechanism by which developing DRG neurons gain independence from NGF has not been determined. We used anin vitromodel of DRG neuronal development to test hypotheses that independence from NGF in mature DRG neurons could be caused by developmental regulation of either elements of the NGF withdrawal signal transduction pathway or of proteins important for activation of the apoptosis output pathway.Interruption of phosphotidylinositol-3 kinase activation, by treatment with the specific inhibitor LY294002, resulted in apoptosis in immature but not mature DRG neurons in a manner similar to that observed with NGF withdrawal. Further downstream along the signal transduction pathway, c-JUN phosphorylation occurred in both immature and mature DRG neurons after NGF withdrawal or treatment with LY294002, despite the fact that the older neurons did not undergo apoptosis. In contrast, the ratio of expression of the proapoptotic genebaxto antiapoptotic genebcl-xLwas many times higher in immature than mature neurons, bothin vivoandin vitro.Taken together, these results strongly suggest that developmental regulation of NGF withdrawal-induced apoptosis in DRG occurs via control of the relative level of expression of members of thebcl-2gene family.
Selective Innervation of Neostriatal Interneurons by a Subclass of Neuron in the Globus Pallidus of the Rat
Authors: Bevan Mark D. , Booth Philip A. C. , Eaton Sean A. , Bolam J. Paul 
Published: April 2018

A subpopulation of neurons in the globus pallidus projects to the neostriatum, which is the major recipient of afferent information to the basal ganglia. Given the moderate nature of this projection, we hypothesized that the pallidostriatal projection might exert indirect but powerful control over principal neuron activity by targeting interneurons, which comprise only a small percentage of neostriatal neurons. This was tested by the juxtacellular labeling and recording of pallidal neurons in combination with immunolabeling of postsynaptic neurons.In addition to innervating the subthalamic nucleus and output nuclei, 6 of 23 labeled pallidal neurons projected to the neostriatum. Both the firing characteristics and the extent of the axonal arborization in the neostriatum were variable. However, light and electron microscopic analysis of five pallidostriatal neurons revealed that each neuron selectively innervated neostriatal interneurons. A large proportion of the boutons of an individual axon (19–66%) made contact with parvalbumin-immunoreactive interneurons. An individual parvalbumin-immunoreactive neuron (n= 27) was apposed on average by 6.7 boutons (SD = 6.1) from a single pallidal axon (n= 2). Individual pallidostriatal boutons typically possessed more than one symmetrical synaptic specialization. In addition, 3–32% of boutons of axons from four of five pallidal neurons contacted nitric oxide synthase-immunoreactive neurons. Descending collaterals of pallidostriatal neurons were also found to make synaptic contact with dopaminergic and GABAergic neurons of the substantia nigra. These data imply that during periods of cortical activation, individual pallidal neurons may influence the activity of GABAergic interneurons of the neostriatum (which are involved in feed-forward inhibition and synchronization of principle neuron activity) while simultaneously patterning neuronal activity in basal ganglia downstream of the neostriatum.
Maternal Deprivation Effect on the Infant’s Neural Stress Markers Is Reversed by Tactile Stimulation and Feeding But Not by Suppressing Corticosterone
Authors: van Oers Helga J.J. , de Kloet E. Ronald , Whelan Tara , Levine Seymour 
Published: April 2018

After 24 hr of maternal deprivation, significant elevations in ACTH and the naturally occurring glucocorticoid corticosterone (CORT) are observed during the stress-hyporesponsive period. The deprived pups also showed in the paraventricular nucleus (PVN) a marked increase of stress-inducedc-fosmRNA and a reduction of corticotropin-releasing hormone (CRH) and glucocorticoid receptor (GR) mRNA; in hippocampal CA1, a reduction of the mineralocorticoid receptor (MR) and GR was observed. Here, we examined whether these changes are reversed by (1) preventing the elevations of CORT characteristic for the 11-d-old deprived pups by administering the synthetic glucocorticoid dexamethasone (DEX); or (2) reinstating some aspects of maternal behavior. The pups were either (1) left undisturbed, (2) stroked, or (3) stroked and episodically fed by cheek cannulation. At postnatal day 12, peripheral and neural stress markers were measured. Nondeprived animals served as controls.Experiment 1 demonstrates that although CORT was kept low by DEX, the central effects on CORT receptors, CRH, andc-fosmRNA were still present, except for MR in hippocampal CA1. Experiment 2 shows that stroking alone prevented the stress-induced rise in ACTH andc-fosmRNA and in the reduction in CRH and MR mRNA. In pups that were fed and stroked, CORT and GR mRNA resembled nondeprived controls. In conclusion, the changes in peripheral endocrine responses and in the brain cannot be attributed to the effect of elevated CORT concentrations, which are characteristic of the maternally deprived neonate. However, reinstating some components of the dams’ nurturing behavior can reverse the effects evoked by maternal deprivation.
The Electrical Properties of Auditory Hair Cells in the Frog Amphibian Papilla
Authors: Smotherman Michael S. , Narins Peter M. 
Published: April 2018

The amphibian papilla (AP) is the principal auditory organ of the frog. Anatomical and neurophysiological evidence suggests that this hearing organ utilizes both mechanical and electrical (hair cell-based) frequency tuning mechanisms, yet relatively little is known about the electrophysiology of AP hair cells. Using the whole-cell patch-clamp technique, we have investigated the electrical properties and ionic currents of isolated hair cells along the rostrocaudal axis of the AP.Electrical resonances were observed in the voltage response of hair cells harvested from the rostral and medial, but not caudal, regions of the AP. Two ionic currents,ICaandIK(Ca), were observed in every hair cell; however, their amplitudes varied substantially along the epithelium. Only rostral hair cells exhibited an inactivating potassium current (IA), whereas an inwardly rectifying potassium current (IK1) was identified only in caudal AP hair cells.Electrically tuned hair cells exhibited resonant frequencies from 50 to 375 Hz, which correlated well with hair cell position and the tonotopic organization of the papilla. Variations in the kinetics of the outward current contribute substantially to the determination of resonant frequency.ICaandIK(Ca)amplitudes increased with resonant frequency, reducing the membrane time constant with increasing resonant frequency. We conclude that a tonotopically organized hair cell substrate exists to support electrical tuning in the rostromedial region of the frog amphibian papilla and that the cellular mechanisms for frequency determination are very similar to those reported for another electrically tuned auditory organ, the turtle basilar papilla.
Brain Mechanisms of Propofol-Induced Loss of Consciousness in Humans: a Positron Emission Tomographic Study
Authors: Fiset Pierre , Paus Tomás , Daloze Thierry , Plourde Gilles , Meuret Pascal , Bonhomme Vincent , Hajj-Ali Nadine , Backman Steven B. , Evans Alan C. 
Published: April 2018

In the present study, we used positron emission tomography to investigate changes in regional cerebral blood flow (rCBF) during a general anesthetic infusion set to produce a gradual transition from the awake state to unconsciousness. Five right-handed human volunteers participated in the study. They were given propofol with a computer-controlled infusion pump to achieve three stable levels of plasma concentrations corresponding to mild sedation, deep sedation, and unconsciousness, the latter defined as unresponsiveness to verbal commands. During awake baseline and each of the three levels of sedation, two scans were acquired after injection of an H215O bolus. Global as well as regional CBF were determined and correlated with propofol concentrations. In addition, blood flow changes in the thalamus were correlated with those of the entire scanned volume to determine areas of coordinated changes.In addition to a generalized decrease in global CBF, large regional decreases in CBF occurred bilaterally in the medial thalamus, the cuneus and precuneus, and the posterior cingulate, orbitofrontal, and right angular gyri. Furthermore, a significant covariation between the thalamic and midbrain blood flow changes was observed, suggesting a close functional relationship between the two structures.We suggest that, at the concentrations attained, propofol preferentially decreases rCBF in brain regions previously implicated in the regulation of arousal, performance of associative functions, and autonomic control. Our data support the hypothesis that anesthetics induce behavioral changes via a preferential, concentration-dependent effect on specific neuronal networks rather than through a nonspecific, generalized effect on the brain.
Spatial Attention Deficits in Patients with Acquired or Developmental Cerebellar Abnormality
Authors: Townsend Jeanne , Courchesne Eric , Covington James , Westerfield Marissa , Harris Naomi Singer , Lyden Patrick , Lowry Timothy P. , Press Gary A. 
Published: April 2018

Recent imaging and clinical studies have challenged the concept that the functional role of the cerebellum is exclusively in the motor domain. We present evidence of slowed covert orienting of visuospatial attention in patients with developmental cerebellar abnormality (patients with autism, a disorder in which at least 90% of all postmortem cases reported to date have Purkinje neuron loss), and in patients with cerebellar damage acquired from tumor or stroke. In spatial cuing tasks, normal control subjects across a wide age range were able to orient attention within 100 msec of an attention-directing cue. Patients with cerebellar damage showed little evidence of having oriented attention after 100 msec but did show the effects of attention orienting after 800–1200 msec. These effects were demonstrated in a task in which results were independent of the motor response. In this task, smaller cerebellar vermal lobules VI–VII (from magnetic resonance imaging) were associated with greater attention-orienting deficits.Although eye movements may also be disrupted in patients with cerebellar damage, abnormal gaze shifting cannot explain the timing and nature of the attention-orienting deficits reported here. These data may be consistent with evidence from animal models that suggest damage to the cerebellum disrupts both the spatial encoding of a location for an attentional shift and the subsequent gaze shift. These data are also consistent with a model of cerebellar function in which the cerebellum supports a broad spectrum of brain systems involved in both nonmotor and motor function.
Ultrastructural Localization of the α4-Subunit of the Neuronal Acetylcholine Nicotinic Receptor in the Rat Substantia Nigra
Authors: Arroyo-Jiménez Maria del Mar , Bourgeois Jean-Pierre , Marubio Lisa M. , Le Sourd Anne-Marie , Ottersen Ole Petter , Rinvik Eric , Fairén Alfonso , Changeux Jean-Pierre 
Published: April 2018

The distribution of the α4-subunit of the neuronal nicotinic acetylcholine receptor (nAChR) in the rat brain was examined at light and electron microscopy levels using immunohistochemical staining. In the present study we demonstrate the specificity, in both tissue homogenates and brain sections, of a polyclonal antibody raised against the rat nAChR α4-subunit. The characterization of this antibody involved: (1) Western blot analysis of rat brain homogenates and membrane extracts from cells previously transfected with diverse combinations of neuronal nAChR subunits, and (2) immunohistochemistry using transfected cells and rat brain tissue.At the light microscope level, the α4-subunit-like-immunoreactivity (LI) was widely distributed in the rat brain and matched the distribution of the α4-subunit transcripts observed previously byin situhybridization. Strong immunohistochemical labeling was detected in the mesencephalic dopaminergic nuclei. The nAChRs in this region are thought to be responsible for the modulation of dopaminergic transmission. The neurotransmitter identity of α4-immunolabeled neurons in the substantia nigra pars compacta (SNpc) and the ventral tegmental area was thus assessed by investigating the possible colocalization of the nAChR α4-subunit with tyrosine hydroxylase using confocal microscopy. The double labeling experiments unambiguously indicated that the α4-subunit-LI is present in dopaminergic neurons.At the electron microscope level, the neurons in the SNpc exhibited α4-subunit-LI in association with a minority of postsynaptic densities, suggesting that the α4-subunit may be a component of functional nAChRs mediating synaptic transmission between midbrain cholinergic neurons and mesencephalic dopaminergic neurons.