bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of acidic amino acid antagonists upon the spectral properties of carp horizontal cells: circuitry of the outer retina
Authors: Mangel SC , Ariel M , Dowling JE
Published: March 2018

The acidic amino acid receptor antagonists, alpha-methylglutamate and alpha-aminoadipate, were applied to the carp retina to study their effects upon the spectral properties of horizontal cells and to elucidate the synaptic connections between horizontal cells and cones. Application of these antagonists strongly hyperpolarized the L-type cone horizontal cells and reduced the responses of these horizontal cells to red light more than to blue light. Application of Co2+ ions to the retina, a procedure which decreases transmitter release, also hyperpolarized the L-type cone horizontal cells but reduced the response of these horizontal cells to red and blue lights equally. These results suggest that red- or long wavelength-sensitive cones release a different transmitter onto L-type cone horizontal cells than do short wavelength-sensitive cones. Application of the acidic amino acid antagonists also revealed details of the feedback pathway from L- type cone horizontal cells to cones. Previous studies have shown that feedback varies directly with stimulus size and that the effects of feedback on the responses of cones are observed as a transient waveform at response onset (a large, hyperpolarizing potential that is quickly followed by a smaller plateau potential). Application of the acidic amino acid antagonists at a dose which partially hyperpolarized the horizontal cells selectively enhanced the response of the cells to blue lights, when full field, and not spot, stimuli were used. The antagonists also eliminated the transient at response onset. These findings are consistent with the presence of a feedback pathway from L- type cone horizontal cells to short wavelength cones but not to long (red-sensitive) cones.
Solubilization of peripheral benzodiazepine-binding sites from rat kidney
Authors: Gavish M , Fares F
Published: March 2018

The ability of a variety of detergents to solubilize peripheral benzodiazepine-binding sites from rat kidney was tested. Of all the detergents tested, only digitonin was found to be suitable for solubilization. This detergent solubilized 21% of the binding activity; 47% was inactivated, and 32% remained in the pellet. Specific binding of [3H]Ro 5–4864 to membrane-bound and solubilized peripheral benzodiazepine-binding sites was saturable, yielding a linear Scatchard plot (r = 0.96). KD values obtained for the membrane-bound and solubilized peripheral benzodiazepine binding sites were 3.9 +/- 0.4 nM and 5.4 +/- 0.4 nM, respectively. Respective Bmax values were 4.6 +/- 0.5 and 1.9 +/- 0.2 pmol/mg of protein. The KD value for the solubilized material obtained from kinetic experiments was 5.3 +/- 0.6 nM. The potency of PK 11195, Ro 5–4864, diazepam, flurazepam, chlordiazepoxide, Ro 15–1788, methyl-beta-carboline-3-carboxylate, and clonazepam to displace bound [3H]Ro 5–4864 from peripheral binding sites was similar in the membrane-bound and the soluble states. Most of the binding activity of the solubilized binding sites was destroyed by heating at 60 degrees C for 30 min or by treatment with 2 M guanidinium chloride or 4 M urea. More than 95% of the binding activity of the solubilized binding sites was retained after 18 hr at 4 degrees C, and more than 60% was retained after 4 days at the same temperature. These results indicate that the binding characteristics of peripheral benzodiazepine-binding sites extant in the membrane-bound state are retained after solubilization.
Stereospecific opiate-binding sites occur in coated vesicles
Authors: Bennett DB , Spain JW , Laskowski MB , Roth BL , Coscia CJ
Published: March 2018

We prepared clathrin-coated vesicles from bovine forebrain utilizing sucrose or deuterium oxide-Ficoll density gradient centrifugation followed by permeation chromatography. Homogeneity was monitored by electron microscopy (EM) and sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). EM revealed that the predominant (up to 98% of the total) organelles were coated vesicles and empty hexagonal baskets. Diameters of the coated vesicles ranged from 37 to 120 nm with a mean of 65.2 +/- 2.2. Upon SDS-PAGE of the coated vesicle fraction, the most prominent band appeared at 180,000 daltons. There were also three additional bands at 100,000, 50,000 and 35,000 daltons, giving the overall pattern characteristic of coated vesicles. Both 0.5 nM tritiated naltrexone and etorphine displayed specific binding to coated vesicles. Naltrexone binding in coated vesicles from gradient fractions was increased 2.5-fold over the original 100,000 X g pellet. An additional 4-fold enrichment in specific binding was observed after permeation chromatography which was concomitant with an increase in the volume density of coated vesicles in electron micrographs. Naltrexone binding was stereospecific and etorphine binding was inhibited by 100 mM NaCl (40%). Both naltrexone and etorphine binding were inhibited by 50 microM guanyl-5′-yl imidodiphosphate (40 to 50%). In summary, purified bovine brain-coated vesicles contained high affinity stereospecific opiate alkaloid-binding sites with characteristic opioid binding properties.
The role of the polymorphonuclear leukocyte in hyperalgesia
Authors: Levine JD , Gooding J , Donatoni P , Borden L , Goetzl EJ
Published: March 2018

The results of recent studies of the mechanism of leukotriene B4- induced hyperalgesia suggest a dependence on polymorphonuclear leukocytes (PMNLs). In this study, we addressed the contribution of PMNLs to hyperalgesia evoked by the peptide chemotactic factors N- formyl-methionyl-leucyl-phenylalanine (fMLP) and the anaphylatoxin fragment of the fifth component of the complement pathway (C5a). Local injection of glycogen, which attracts but does not activate PMNLs, produced a marked shift to the left (toward lower concentrations) in the concentration dependence curve of fMLP-induced hyperalgesia. In addition, PMNL repletion by transfusion with syngeneic PMNLs reestablished fMLP-induced hyperalgesia in PMNL-depleted rats. Finally, supernatants from rat and human PMNLs, that had been stimulated with fMLP in vitro, produced hyperalgesia in PMNL-depleted rats. Preliminary characterization of the hyperalgesia-inducing activity released by stimulated PMNLs indicated that it is lipid in nature. The nonsteroidal anti-inflammatory indomethacin did not attenuate C5a and fMLP-induced hyperalgesia. Thus, the hyperalgesia produced by fMLP and C5a is similar to that produced by leukotriene B4 in that it is dependent on PMNLs and independent of the cyclo-oxygenation of arachidonic acid. Taken together, these data suggest that structurally diverse PMNL- chemotactic factors produce hyperalgesia by a novel mechanism, involving PMNL-derived factors.
Age-related fiber order in the optic tract of the ferret
Authors: Walsh C , Guillery RW
Published: March 2018

In the ferret's optic tract, the position of retinofugal fibers has been related to their relative age by preferentially labeling the oldest fibers. It has been found that fiber order perpendicular to the pial surface represents the sequence of axon arrivals in the optic tract, the fibers furthest from the pia being the oldest. Immature ferrets, less than 34 days post-conception (E34), were given intravitreal injections of lectin-bound horseradish peroxidase or of 3H- amino acids. After survival times of 24 hr or less, the contralateral optic tract was uniformly labeled, whereas with longer survival times unlabeled zones were seen next to the pial border. These unlabeled zones were largest after injections into the youngest animals but were never seen when injections were made after E34, no matter what the survival time. The unlabeled zones were seen in the tracts of animals having unlabeled regions in the periphery of the retina. The unlabeled retinal ganglion cells are interpreted as ganglion cells formed after the injection was made, and unlabeled axons next to the pia in the tract are interpreted as the axons of these youngest cells. Some irregularities in the layered arrangement of the tract are described, and the fiber order in the tract is contrasted with that in the optic nerve behind the eye. It is shown that tract order is partially independent of order in the intraorbital part of the optic nerve. Between the retina and the optic tract, a sorting of fibers occurs not only in terms of the pattern of decussation, but also in terms of fiber age.
Light-evoked contraction of the photosensitive iris of the frog
Authors: Kargacin GJ , Detwiler PB
Published: March 2018

Smooth muscle cells of the frog iris sphincter contain rhodopsin and contract in response to light. The mechanism of light-evoked contraction was studied with particular attention paid to the role of calcium. The contractile proteins of the sphincter smooth muscle cell can be activated by an increase in intracellular calcium. Light-evoked contraction, however, is not accompanied by a measurable change in membrane potential and occurs in the absence of extracellular Na+ and/or Ca2+, as well as in the presence of isotonic KCI. Maximum light- evoked tension is reduced by exposure to Ca2+-free solutions containing EGTA and high K+ and is restored by incubation in solutions containing Ca2+. The restored response, which persists after return to Ca2+-free solution, depends on the concentration of Ca2+ in the incubating solution and on the duration of the incubation. The results support the conclusion that light produces contraction of the iris sphincter by causing the release of Ca2+ from an intracellular storage site.
Changes in the structure of synapses associated with learning
Authors: Horn G , Bradley P , McCabe BJ
Published: March 2018

Two experiments were conducted to investigate the effects of training on a region of the chick brain known to be critically involved in imprinting, the intermediate and medial extent of the hyperstriatum ventrale (IMHV). In the first experiment, three groups of chicks were used: (i) dark-reared (n = 9), (ii) trained for 20 min (n = 17), and (iii) trained for 140 min (n = 7). Chicks were trained by exposing them when they were approximately 21 hr old to a flashing red light. Chicks were killed when they were approximately 30 hr old and blocks of tissue were removed from the right and left IMHV. Stereological techniques were used to measure from electron micrographs the numerical density of dendritic spine and shaft synapses and the length of the postsynaptic density of these synaptic junctions. There was a significant effect of training only in the left IMHV and on only one measure, the overall mean length of the postsynaptic density of spine synapses, SPL. This measure was significantly greater by 17.2% in chicks trained for 140 min than in dark-reared controls. There was no significant effect of training for 20 min. In the second experiment one group of chicks (n = 15) was exposed to a rotating red box for a total of 3 hr. Another group of chicks was dark-reared (n = 15). The chicks were killed when they were approximately 46 hr old. Samples from the hyperstriatum accessorium and IMHV of the right and left sides were analyzed. Training was associated with a significant change, an increase, only of SPL in the left IMHV.(ABSTRACT TRUNCATED AT 250 WORDS)
Corticotropin-releasing factor receptors are widely distributed within the rat central nervous system: an autoradiographic study
Authors: De Souza EB , Insel TR , Perrin MH , Rivier J , Vale WW , Kuhar MJ
Published: March 2018

Corticotropin-releasing factor (CRF) receptor-binding sites have been localized and quantified in the rat central nervous system (CNS) by autoradiography with an iodine-125-labeled analogue of ovine CRF substituted with norleucine and tyrosine at amino acid residues 21 and 32, respectively. High affinity and pharmacologically specific receptor- binding sites for CRF were found in discrete areas within the rat CNS. CRF receptors were highly concentrated in laminae 1 and 4 throughout the neocortex, the external plexiform layer of the olfactory bulb, the external layer of the median eminence, several cranial nerve nuclei in the brainstem including the facial, oculomotor, trochlear, vestibulocochlear, and trigeminal nuclei, the deep cerebellar nuclei, and the cerebellar cortex. Moderate concentrations of CRF receptors were present in the olfactory tubercle, caudate-putamen, claustrum, nucleus accumbens, nucleus of the diagonal band, basolateral nucleus of the amygdala, paraventricular nucleus of the hypothalamus, mammillary peduncle, inferior and superior olives, medullary reticular formation, inferior colliculus, and brainstem nuclei including tegmental, parabrachial, hypoglossal, pontine, cuneate, and gracilis nuclei, and in spinal cord. Lower densities of CRF binding were found in the bed nucleus of the stria terminalis, central and medial amygdaloid nuclei, and regions of the thalamus, hypothalamus, hippocampus, and brainstem. The distribution of CRF-binding sites generally correlates with the immunocytochemical distribution of CRF pathways and with the pharmacological sites of action of CRF. These data strongly support a physiological role for endogenous CRF in regulating and integrating functions in the CNS.
Analysis of microspike movements on the neuronal growth cone
Authors: Bray D , Chapman K
Published: March 2018

Growth cones of chick sensory ganglion neurons in tissue culture were photographed at 60-sec intervals as they advanced over the substratum. Numbers of microspikes (or “filopodia”) were recorded together with the time and position of their appearance, their rate of elongation, their lateral movements, their lifespan, and the position and manner of their disappearance. All microspikes go through cycles of extension, lateral movement, and shortening. These are irregular and unpredictable but show systematic differences depending on where on the growth cone they occur. At the leading edge of the growth cone microspike extension occurs at highest frequency and microspike shortening occurs at the lowest frequency; when the latter occurs in this region it often involves the advance of the margin of the cell in the form of a lamellipodium. Microspike loss occurs most often at the base of the growth cone, usually by the retraction of the microspike into the cell. Calculations of the gain and loss of microspikes at different regions of the growth cone show that they undergo a net retrograde flow, the rate of which is correlated with the forward advance of the growth cone. Individual microspikes can also move backward from the growth cone onto the axon (or “neurite”), an event that occurs most often on adhesive substrata. Our observations support a direct role of microspike movement in the advance of the growth cone. The primary force for axonal elongation appears to be the contraction of microspikes pulling the leading margin of the growth cone forward. At more proximal and peripheral regions of the growth cone, microspikes undergo a retrograde sweeping motion, followed by retraction into the cell, which may also contribute to the forward movement of the growth cone. We interpret these movements as arising from a flow of actin filaments and associated proteins which are incorporated into microspikes and lamellipodia at the leading edge of the growth cone, passing backward, and being deposited into the actin-rich membrane- associated cortex of the axonal cylinder.
The circadian pacemaker in the Aplysia eye sends axons throughout the central nervous system
Authors: Olson LM , Jacklet JW
Published: March 2018

Each eye of Aplysia contains a population of electrically coupled pacemaker neurons whose synchronous activity can be recorded from the optic nerve as a compound action potential (CAP). The CAP frequency continues to show a circadian rhythm even when the eye is isolated from the animal and maintained in constant conditions, and thus it contains an autonomous circadian pacemaker, which may reside in the pacemaker neurons. The pacemaker neurons, along with retinal photoreceptors, send axons out of the optic nerve, which connects to the cerebral ganglion of the central nervous system (CNS). Pacemaker neurons, but not photoreceptors, may contain an aminergic transmitter, possibly dopamine (DA). We describe the central projections of optic nerve fibers using horseradish peroxidase filling of the cut optic nerve, and transport of radiolabeled macromolecules after selective exposure of the eye to [3H] leucine, which labels both pacemaker neurons and photoreceptors. We were able to determine the projections of pacemaker axons by exposing the eye to [3H]-3,4-dihydroxyphenylalanine [( 3H] DOPA and [3H]DA, which is preferentially taken up and transported by the pacemaker neurons. Pacemaker axons project bilaterally to the cerebral, pedal, and pleural ganglia and may extend as far as the abdominal ganglion. We corroborate this anatomical evidence by recording an orthodromic CAP in the optic nerve that had originated in the eye and subsequently recording the CAP in the CNS connectives and nerves that contained [3H]DOPA-labeled fibers. These results suggest that circadian pacemaker information from the eye is widely distributed throughout the CNS, including neural structures known from studies by others to mediate circadian-regulated behaviors, such as locomotion. Thus, Aplysia can now be used as a model system to examine the influence of the central projections of an identified circadian pacemaker on behavior, such as locomotion, at the level of identified central neurons.
Vertical organization of gamma-aminobutyric acid-accumulating intrinsic neuronal systems in monkey cerebral cortex
Authors: DeFelipe J , Jones EG
Published: March 2018

Light and electron microscopic methods were used to examine the neurons in the monkey cerebral cortex labeled autoradiographically following the uptake and transport of [3H]-gamma-aminobutyric acid (GABA). Nonpyramidal cell somata in the sensory-motor areas and primary visual area (area 17) were labeled close to the injection site and at distances of 1 to 1.5 mm beyond the injection site, indicating labeling by retrograde axoplasmic transport. This labeling occurred preferentially in the vertical dimension of the cortex. Prior injections of colchicine, an inhibitor of axoplasmic transport, abolished all labeling of somata except those within the injection site. In each area, injections of superficial layers (I to III) produced labeling of clusters of cell somata in layer V, and injections of the deep layers (V and VI) produced labeling of clusters of cell somata in layers II and III. In area 17, injections of the superficial layers produced dense retrograde cell labeling in three bands: in layers IVC, VA, and VI. Vertically oriented chains of silver grains linked the injection sites with the resulting labeled cell clusters. In all areas, the labeling of cells in the horizontal dimension, i.e., on each side of an injection, was insignificant. Electron microscopic examination of labeled neurons confirms that the neurons labeled at a distance from an injection site are nonpyramidal neurons, many with somata so small that they would be mistaken for neuroglial cells light microscopically. They receive few axosomatic synapses, most of which have symmetric membrane thickenings. The vertical chains of silver grains overlie neuronal processes identifiable as both dendrites and myelinated axons, but unmyelinated axons may also be included. The clusters of [3H]GABA-labeled cells are joined to one another and to adjacent unlabeled cells by many junctional complexes, including puncta adherentia and multi-lamellar cisternal complexes. We conclude that groups of GABA-transporting neurons are likely to use GABA as a transmitter and form an inhibitory, bidirectional system of connections that join together cells in superficial and deep layers of functional cortical columns; intrinsic, horizontal GABAergic connections are either far less significant in the organization of the cerebral cortex or are not labeled by this method.(ABSTRACT TRUNCATED AT 400 WORDS)
Pharmacological properties of gamma-aminobutyric acid-, glutamate-, and aspartate-induced depolarizations in cultured astrocytes
Authors: Kettenmann H , Schachner M
Published: March 2018

Differentiated glial fibrillary acidic protein-positive astrocytes in homogeneous cultures of early postnatal rat cerebral hemispheres respond by membrane depolarization to gamma-aminobutyric acid (GABA), glutamate, and aspartate with a threshold concentration of approximately 10(-5) M. The GABA-induced depolarization is antagonized by two blockers of the neuronal GABAA receptor, picrotoxin and bicuculline, but is not affected by the uptake blockers beta-alanine or nipecotic acid. An agonist of the GABAA receptor, muscimol, produces a dose-response curve similar to that of GABA, whereas the agonist of the GABAB receptor, baclofen, did not alter the membrane potential. When repetitive pulses of GABA are given to one cell, its responsiveness depends on the time interval between pulses. Within 30 sec after termination of the first pulse the cell remains unresponsive to the second pulse. With increased time intervals between the pulses, reactivity toward GABA recovers. Five minutes after the first pulse the cell regains 75% of its initial depolarization peak. Aspartate results in a depolarization similar in size and time course to that induced by glutamate. The glutamate agonists, quisqualate and ibotenate, and kainate are less potent than glutamate. N-Methyl-D-aspartate has no effect on the membrane potential of astrocytes. The pharmacological features of the glutamate response are therefore similar to those of the receptor mediating neuronal glutamate transport.
Identification of major cell classes in the developing mammalian nervous system
Authors: Hockfield S , McKay RD
Published: March 2018

A major difficulty in studying early developmental processes and testing hypotheses of possible cellular mechanisms of development has been the inability to reproducibly identify specific cell types. We have generated monoclonal antibodies that distinguish among major cell types present during mammalian neurogenesis. These antibodies have been used to analyze the development of cellular organization in the early nervous system. Monoclonal antibody Rat-401 identifies a transient radial glial cell in the embryonic rat central nervous system (CNS) that is temporally and spatially suited to guide neuronal migration. Rat-401 also identifies a peripheral non-neuronal cell that may establish axon routes from the CNS to the periphery. Monoclonal antibody Rat-202 recognizes an antigen present in early axons, their growth cones, and filopodia, and has allowed us to follow early axons and observe the structures they contact. Two other antibodies that recognize axons demonstrate antigenically distinct phases in axon development. In addition, we report a marker for another cell class present in the developing nervous system, the endothelial cells that give rise to the CNS vasculature.
Is reactive gliosis a property of a distinct subpopulation of astrocytes?
Authors: Miller RH , Abney ER , David S , Ffrench-Constant C , Lindsay R , Patel R , Stone J , Raff MC
Published: March 2018

We have shown previously that the A2B5 monoclonal antibody distinguishes two types of glial fibrillary acidic protein-containing astrocytes in semithin frozen sections of adult rat optic nerve: A2B5- (type-1) astrocytes are found mainly at the periphery of the nerve, where they form the glial limiting membrane, while A2B5+ (type-2) astrocytes are found mainly in the interior of the nerve and constitute more than 65% of the astrocytes in the adult optic nerve. In the present study we show that although most astrocytes in semithin frozen sections of adult rat corpus callosum and optic nerve are A2B5+, the great majority of reactive astrocytes in similar sections of corpus callosum examined 20 weeks after a stab lesion, and in optic nerve examined 20 weeks after adult transection, are A2B5-. Although both A2B5+ and A2B5- astrocytes are stimulated to synthesize DNA in the first week after transection, adult optic nerves examined 20 weeks after transection contain only half as many astrocytes as do normal optic nerves: While A2B5+ astrocytes are reduced almost 10-fold, A2B5- astrocytes are increased by about 25%. We consider the simplest interpretation of these findings to be that type-1 astrocytes are largely responsible for forming glial scars in adult white matter following either a stab lesion or Wallerian degeneration and that in transected optic nerves, most type-2 astrocytes eventually die, possibly because they depend on axons for their long-term survival.
Immunoreactive dynorphin B in sacral primary afferent fibers of the cat
Authors: Basbaum AI , Cruz L , Weber E
Published: March 2018

Immunocytochemical analysis of the distribution of dynorphin B terminals in the sacral spinal cord of the cat revealed a pattern of staining very similar to that produced with antisera directed against the primary afferent derived, putative neurotransmitter, vasoactive intestinal polypeptide. Labeled axons and terminals were concentrated in lamina I and V and there was dense fiber staining in the tract of Lissauer. Of particular interest was the presence of immunoreactive axons in attached dorsal rootlets. To specifically focus on the possibility that some of the sacral primary afferent fibers are dynorphin-immunoreactive, we first tried to increase perikaryal labeling in the sacral dorsal root ganglia by topical treatment with colchicine. This did not produce immunoreactive labeling of cell bodies in the ganglia. Unilateral multiple dorsal rhizotomy (L5 to coccygeal 1), however, significantly decreased the staining of dynorphin- immunoreactive axons and terminals in the tract of Lissauer and in the dorsal horn of sacral segments ipsilateral to the deafferentation. No changes were detected in the lumbar cord. Finally, radioimmunoassay of caudal lumbar and sacral dorsal root ganglia was performed. Measurable immunoreactivity was found in all ganglia assayed, but, consistent with the histochemical analysis, sacral ganglia contained the highest concentration of immunoreactive dynorphin B. These data indicate that a significant component of the sacral spinal cord dynorphin terminal immunoreactivity derives from primary afferent fibers.(ABSTRACT TRUNCATED AT 250 WORDS)
Endocrine regulation of the form and function of axonal arbors during insect metamorphosis
Authors: Levine RB , Truman JW , Linn D , Bate CM
Published: March 2018

By discrete manipulation of the endocrine cues that control insect metamorphosis, it has been possible to examine the mechanisms governing the growth of neural processes during development. During the transition from larva to pupa in the hawkmoth, Manduca sexta, identified sensory neurons reorganize their central projections to evoke a new behavior--the gintrap reflex. Topical application of a juvenile hormone analog to the peripheral cell bodies of these sensory neurons during a critical period of development caused them to retain their larval commitment rather than undergo pupal development with the rest of the animal. The sensory neurons retained the larval arborization pattern within the pupal CNS and were unable to evoke the gin-trap reflex. Thus, the hormonal environment of the cell body is critical for controlling growth and synapse formation by distant axonal processes.
The somatosensory thalamus of the raccoon: properties of single neurons responsive to light mechanical stimulation of the forepaw
Authors: Warren S , Kelahan AM , Pubols BH
Published: March 2018

These studies were undertaken to characterize the discharge properties of single neurons of the raccoon thalamic ventrobasal complex (VB) that respond to light mechanical stimulation of the glabrous surfaces of the forepaw. Microelectrodes were used to record the extracellular activity of 146 cells in anesthetized raccoons, and all neurons were histologically verified as falling within or along the boundaries of VB. Sixty-one neurons were tested for activation by electrical stimulaton of primarily somatosensory cortex. Of these, 88% were antidromically activated, 5% were synaptically activated, and the remaining 7% were unresponsive. Out of the total sample of 146 neurons, 136 had peripheral receptive fields (RFs) that were restricted to glabrous skin and revealed properties of modality and place-specificity predictable through knowledge of properties of primary mechanoreceptive afferents. Rapidly adapting (RA) neurons accounted for 77% of this modality-place-specific sample, while 19% were slowly adapting (SA), and 4% revealed properties indicative of input from Pacinian afferents (Pc). Absolute displacement thresholds were comparable for RA and SA neurons (range = 6–415 micron). Palmar RF areas (range = 3.3–328 mm2) were significantly larger than digital RF areas (range = 0.5–98.2 mm2). As defined by exponents (b) of power functions relating instantaneous discharge frequency to displacement ramp velocity, SA neurons formed a single, homogeneous group (range of values of b = 0.633–0.720). However, RA neurons fell into three distinct groups: those showing relatively steep functions (b = 0.559–0.938), those showing relatively flat functions (b = 0.146–0.334), and those showing discontinuous, or step, functions. A small number of neurons (7% of total sample) revealed “complex” properties, not predictable from knowledge of properties of primary afferents. These included five neurons whose RFs encompassed both glabrous and hairy skin, and several linear orientation, or “tactile edge,” detectors. The present results, in conjunction with those of earlier studies of the raccoon dorsal column- medial lemniscal system, lead to the conclusion that different types of information transformation are emphasized at different levels of the system. Intramodality convergences (increases in RF area) occur primarily within the cuneothalamic relay, while changes in the coding of quantitative information are primarily a function of VB neurons. The appearance of linear orientation detectors--a type of tactile “feature detector”--indicates that the synthesis of information regarding complex spatial properties of stimuli has its beginnings within the somatosensory thalamus.
Contextual control of trigeminal sensorimotor function
Authors: Berridge KC , Fentress JC
Published: March 2018

Simple actions, such as rhythmic tongue protrusions, forelimb facial strokes, and forelimb flails, are emitted by rats both during taste- elicited ingestion/aversion and during postprandial grooming. This study combined peripheral trigeminal deafferentation with a computer- assisted video analysis of action form to examine the use of cutaneous feedback from the face in action production. Changes in action form after deafferentation were found to be context-dependent: Deformations characterized rhythmic tongue protrusions when emitted in ingestive but not in grooming contexts. The opposite was true for alterations in forelimb action. Further, postprandial grooming as a whole was found to comprise distinct sequentially defined phases. Actions occurring in one highly stereotyped sequence phase were protected from deafferentation effects, although the same actions occurring outside of this phase were not. The results suggest that behavioral context (e.g., grooming versus ingestive set, sequence phase) can shift the integration of sensory guided and endogenous mechanisms that pattern simple actions.
Vestibular signals carried by pathways subserving plasticity of the vestibulo-ocular reflex in monkeys
Authors: Lisberger SG , Pavelko TA
Published: March 2018

The vestibulo-ocular reflex (VOR) is subject to long-term adaptive changes that minimize retinal image slip and keep eye movement equal to and opposite head movement. As a step toward identifying the site of neural changes, we have used a transient vestibular stimulus to study the dynamic response properties of the vestibular signals carried by the modifiable pathways. In normal monkeys, “rapid changes in head velocity” (30 degrees/sec in 50 msec) evoke a VOR that has a slight overshoot and reaches a steady-state gain (eye velocity divided by head velocity) of 1.0. Adaptation to magnifying spectacles causes changes in both the steady-state gain and the degree of overshoot in the eye velocity of the VOR. When the steady-state gain is decreased, the transient overshoot increases, so that peak eye velocity is twice steady-state. When the steady-state gain is increased, the overshoot decreases, so that peak eye velocity is nearly equal to steady-state. The discharge of vestibular primary afferents suggests an explanation for the inverse relationship between the transient overshoot and the steady-state gain of the VOR. In normal monkeys, 73 afferents showed a range of transient responses during rapid changes in head velocity. The afferents with the most regular spontaneous discharge had little overshoot in firing rate. Afferents with less regular discharge had large overshoots in firing; the peak change in firing was 2–6 X the steady-state change. We suggest that the large overshoot in eye velocity when VOR gain is low represents the contribution of vestibular signals from afferents with large transient responses.(ABSTRACT TRUNCATED AT 250 WORDS)
Changes in excitability induced by herpes simplex viruses in rat dorsal root ganglion neurons
Authors: Mayer ML , James MH , Russell RJ , Kelly JS , Pasternak CA
Published: March 2018

The physiological properties of rat sensory neurons infected with herpes simplex type 1 viruses and maintained in cell culture were studied using intracellular recording techniques. Two syncytial (cell fusing) and two nonsyncytial strains of virus were examined; individual strains of virus had different effects on neuronal excitability. The nonsyncytial viruses caused a loss of tetrodotoxin-sensitive low- threshold action potentials and blocked hyperpolarization-activated inward rectification, but did not alter the resting membrane potential, depolarization-activated outward rectification, or render the cells leaky. These effects develop progressively over the period 5–15 hr postinfection. One syncytial strain of virus induced spontaneous electrical activity that appeared to be the result of discrete electrical coupling between sensory neuron processes; as a result, action potential discharge is synchronized in coupled neurons. A second syncytial strain of virus rendered neurons inexcitable; however, in these experiments the input resistance fell to low values, possibly as a result of extensive coupling between sensory neurons. Viral replication in sensory neurons was demonstrable with indirect immunofluorescence using an antibody to herpes simplex viruses and correlated with the onset of virally induced changes in excitability. Virally triggered changes in excitability were blocked by the specific herpes virus antimetabolite acyclovir, suggesting that viral adsorption and penetration are by themselves insufficient to evoke changes in excitability. These results suggest that herpes viruses have selective effects on the excitable mechanisms in sensory neurons that are not simply the result of a general loss of membrane conductances or the disruption of transmembrane ion gradients.
Premotor cortex neurons in macaques: activity before distal and proximal forelimb movements
Authors: Kurata K , Tanji J
Published: March 2018

Single unit activity was examined in the premotor cortex of three awake, behaving macaque monkeys. Premotor cortex (PM) neurons were found to be active in association with a movement involving specifically the distal forelimb. Other PM neurons were active in relation to more proximal forelimb movements. The spatial distribution of neurons related to distal movements differed from that of neurons related to proximal forelimb movements, the former being focused at a postarcuate region near the genu of the arcuate sulcus and the latter being shifted more posteromedially. The distal movement was triggered by one of the three sensory signals: visual, auditory, and vibrotactile. Of 190 PM neurons related to the distal forelimb movements, 123 (65%) showed similar premovement activity changes irrespective of the modality of the triggering signal. However, a number of neurons (35%) responded preferentially to one or two of the three signals. The modality-specific activity before movements distinguishes PM from the caudally adjacent primary motor cortex.
Functional metabolic mapping during forelimb movement in rat. I. Stimulation of motor cortex
Authors: Collins RC , Santori EM , Der T , Toga AW , Lothman EW
Published: March 2018

The quantitative 14C-deoxyglucose (DG) autoradiographic technique has been used to study changes in cerebral metabolism during forelimb movements induced by graded stimulation of motor cortex. Experiments were directed at studying basic physiologic and anatomic aspects of the metabolic changes. Single shocks caused movement without metabolic change, whereas low-frequency trains caused seizures. Repetitive high- frequency train stimuli of short duration (500 Hz for 20 msec) caused jerk movements coupled with DG uptake in pathways. With stimulation of the forelimb motor zone at frequencies of 15–30/min there was prominent activation of cortical columns and strips in ipsilateral SI, SII, and MII, and contralateral MI and SI. Higher frequencies (120/min) were required to cause significant changes in DG in subcortical circuits. The most prominent changes occurred within a longitudinal corridor in dorsal thalamus and a ventral corridor in second-order sites in basal ganglia. Metabolic activation also occurred in contralateral cerebellum, the cuneate nucleus, and dorsal horn of the cervical spinal cord. Changes in these latter two sites were largely eliminated by removing feedback sensory activity. Stimulation of the forelimb sensory zone activated different sites in caudatoputamen and thalamus but similar zones in midbrain and cerebellum. The magnitude of the metabolic response in distant sites depended on the frequency of cortical stimulation. Different frequency-response relationships in different sites seemed to reflect the nature of the cortical input as well as differential effects of anesthesia. The pattern of the metabolic response was studied by comparing sites of activation with sites of the anatomic projections from motor and sensory cortical zones. 3H- and 14C-labeled amino acids were used to map the site and relative strength of pathways. Results revealed good correlation between the site of anatomic projection and the site of DG uptake but no consistent relationship between the relative strength of a projection and the magnitude of metabolic change within its field. Changes in glucose utilization with metabolic mapping experiments depend on the nature, strength, and frequency of stimulation; the site and nature of anatomic projection; the effects of anesthesia; and the strength of sensory feedback associated with the induced behavior.
Phorbol esters mimic some cholinergic actions in hippocampal pyramidal neurons
Authors: Malenka RC , Madison DV , Andrade R , Nicoll RA
Published: March 2018

Muscarinic receptor stimulation in the hippocampus has been associated with inositol phospholipid breakdown. In other systems this leads to the formation of inositol trisphosphate and diacylglycerol, which promotes the activation of protein kinase C. Phorbol esters, which directly activate protein kinase C, exhibit high and specific binding in the hippocampus. This, along with the advantages of the hippocampal slice preparation, including direct pharmacological access to a cell population (CA1 pyramidal cells) having clearly defined muscarinic responses, makes this an ideal preparation to examine whether protein kinase C serves as the intracellular signal for muscarinic receptor occupation. Like muscarinic agonists, phorbol esters abolish the slow calcium-activated potassium afterhyperpolarizing potential (AHP) and its underlying current without reducing calcium action potentials. Those phorbol analogs that do not activate kinase C have no effect, suggesting that activation of this enzyme is required to reduce the AHP. The accommodation of spike discharge normally seen during a long depolarizing stimulus is also markedly reduced by phorbol esters as well as by muscarinic receptor activation. However, unlike muscarinic agonists, phorbol esters have no effect on the muscarine-sensitive, voltage-dependent, potassium current termed IM, nor do they consistently cause an increase in input resistance. Moreover, unlike ACh, they do not appear to have a presynaptic inhibitory action on the fast EPSP elicited by orthodromic stimulation. The slow cholinergic EPSP was blocked by phorbol esters, but this could be accounted for by a postsynaptic action. Thus, if inositol phospholipid turnover is involved in mediating muscarinic responses in the hippocampus, the activation of protein kinase C can account for only part of the electrophysiological response.
Differences in transmitter release and number of nerve terminals per motoneuron between two frog muscles
Authors: Yao YM , Weakly JN
Published: March 2018

Recent studies suggest that the number of nerve terminals maintained per motoneuron and perhaps other motoneuron properties (Grinnell and Herrera, 1980a; Grinnell and Trussell, 1983) influence transmitter release. We have examined, in detail, the structure and function of motoneurons innervating two different twitch muscles, the sartorius and the ext. long. dig. IV (e.l.d.) in the adult frog using histochemical and electrophysiological techniques. These studies were undertaken with a view towards learning whether differences in the number of nerve terminals per motoneuron were correlated with differences in transmitter release between motoneurons innervating these two muscles. Moreover, these studies provide detailed, quantitative data that are a necessary prerequisite for carrying out additional studies to examine the possible influence of muscle on transmitter release properties. In low Ca2+-high Mg2+ Ringer's solution, mean quantal content (m) and miniature end-plate potential (MEPP) frequency were larger at sartorius than at e.l.d. end-plates. The mean length of nerve terminals was also found to be greater in sartorius than in e.l.d. muscles. When release was normalized for the difference in terminal length, m remained larger in the sartorius, whereas MEPP frequency in the two muscles was similar. Cell bodies of individual sartorius motoneurons were greater in cross-sectional area and maintained approximately 5.6-fold greater aggregate length of nerve terminals per motoneuron than did e.l.d. motoneurons. This greater aggregate length of nerve terminal contact with their respective target muscles is primarily a result of a greater number of nerve terminals supported by sartorius than by e.l.d. motoneurons.(ABSTRACT TRUNCATED AT 250 WORDS)
Receptive fields of motor neurons underlying local tactile reflexes in the locust
Authors: Siegler MV , Burrows M
Published: March 2018

The receptive fields of motor neurons to a hind leg were mapped by recording intracellularly from their cell bodies or from the muscle fibers they innervate while stimulating mechanoreceptors on the surface of that leg. Each motor neuron is affected by a specific array of receptors that make up its receptive field. Boundaries along the anteroposterior or dorsoventral axes of the leg divide the receptive fields into excitatory and inhibitory regions. Proximodistal boundaries may correspond to the articulations between parts of the leg. Motor neurons that innervate antagonistic muscles have complementary receptive fields, so that the region that is excitatory for one is inhibitory for the other. The receptive fields of the motor neurons overlap. Tactile stimulation therefore leads to a specific local reflex that involves the coordinated movement of the segments of a leg. Five local reflexes are described, each of which moves the leg away from the site of stimulation. Afferents from the external mechanoreceptors do not synapse directly on the motor neurons, but instead on spiking local interneurons, some of which then synapse directly on motor neurons. These local interneurons have smaller receptive fields delineated by the same boundaries, so that the receptive fields of the motor neurons can be constructed from appropriate combinations of them. It is suggested that receptive fields are organized as “functional maps” that are appropriate for particular behavioral responses rather than solely to preserve or refine spatial information.
The brain-specific gene 1B236 is expressed postnatally in the developing rat brain
Authors: Lenoir D , Battenberg E , Kiel M , Bloom FE , Milner RJ
Published: March 2018

The rat brain-specific polypeptide 1B236 was previously characterized by molecular cloning and nucleotide sequence determination of its mRNA. It has been shown to exist in rat brain in discrete neuronal circuits, primarily as a 100,000 Da glycoprotein. We now have determined the time course of expression of 1B236 mRNA and protein in rat brain during fetal and postnatal development, detecting 1B236 mRNA by RNA blotting and assaying 1B236 protein by electroblotting and radioimmunoassay with antibodies against synthetic peptides. By both indices, expression of the 1B236 gene products is found to be a relatively late event in neuronal development. 1B236 mRNA is first detectable in extracts of whole rat brain at Postnatal Day 5 (PD 5) and increases to a maximum concentration at PD 25. In extracts of dissected brain regions, 1B236 mRNA is first detectable at PD 5 in hindbrain and cerebellum, at PD 9 in midbrain/diencephalon, but not until PD 13 in telencephalon. The appearance of 1B236 protein follows a very similar time course to that of its mRNA in both whole brain and dissected brain regions, suggesting that the expression of the protein during development is regulated largely by transcription of its mRNA. The pattern of 1B236 expression was confirmed by immunocytochemical localization of 1B236 protein: Immunoreactive material can be detected first in spinal cord at PD 3-PD 5 and then appears in progressively more rostral brain regions in increasingly older animals. Several brain regions, however, that do not contain 1B236 immunoreactivity in the adult, such as optic nerve and somatic efferent cranial nerve nuclei, show transient expression of 1B236 during postnatal development.(ABSTRACT TRUNCATED AT 250 WORDS)
Localization of muscarinic receptors on cultured myenteric neurons: a combined autoradiographic and immunocytochemical approach
Authors: Buckley NJ , Burnstock G
Published: March 2018

In order to localize the distribution of muscarinic receptors over the surface of cultured myenteric neurons, an autoradiographic procedure for detecting muscarinic receptors (using [3H]propylbenzilylcholine mustard; [3H]PrBCM) has been combined with an immunofluorescence procedure visualizing neuronal morphology (using an antibody raised against rat brain synaptosomes; anti-CTX). Using this technique, muscarinic receptors were localized over discrete areas of the neuronal cell surface. Receptors were seen to be widely distributed over the somata and neurites of 10–20% of cultured myenteric neurons. The greatest concentration of receptors occurred over the cell somata and proximal neurites. Receptors appeared evenly distributed over labeled cell somata, where their density was estimated to be between 30 and 100 receptors/micron2. Distal regions of neurites were labeled intermittently with some varicosities and intervaricosities being labeled while others were unlabeled. Growth cones and nerve endings of labeled neurites were consistently labeled. The ability to localize muscarinic receptors on a subpopulation of immunocytochemically identified neurons enhances our understanding of muscarinic neurotransmission in myenteric neurons and provides an experimental system for the investigation of regulatory influences on neuronal neurotransmitter receptor expression and distribution.