bluuebunny/crossref_metadata_2025 huggingface dataset:
Stimulus-selective properties of inferior temporal neurons in the macaque
Authors: Desimone R , Albright TD , Gross CG , Bruce C
Published: March 2018

Previous studies have reported that some neurons in the inferior temporal (IT) cortex respond selectively to highly specific complex objects. In the present study, we conducted the first systematic survey of the responses of IT neurons to both simple stimuli, such as edges and bars, and highly complex stimuli, such as models of flowers, snakes, hands, and faces. If a neuron responded to any of these stimuli, we attempted to isolate the critical stimulus features underlying the response. We found that many of the responsive neurons responded well to virtually every stimulus tested. The remaining, stimulus-selective cells were often selective along the dimensions of shape, color, or texture of a stimulus, and this selectivity was maintained throughout a large receptive field. Although most IT neurons do not appear to be “detectors” for complex objects, we did find a separate population of cells that responded selectively to faces. The responses of these cells were dependent on the configuration of specific face features, and their selectivity was maintained over changes in stimulus size and position. A particularly high incidence of such cells was found deep in the superior temporal sulcus. These results indicate that there may be specialized mechanisms for the analysis of faces in IT cortex.
The receptor potential and adaptation in the cockroach tactile spine
Authors: French AS
Published: March 2018

The receptor potential in the cockroach tactile spine was measured during mechanotransduction by recording from the afferent axon about 0.5 mm from the sensory ending. The receptor potential was a linear function of spine position, but its amplitude and phase varied with the mean position of the spine. This can be related to the mechanical linkage from the socket of the spine to the sensory ending. The frequency response for mechanotransduction was flat over a frequency range of 0.1 to 100 Hz, after accounting for the cable properties of the axon, and there was no evidence of adaptation. The length constant and membrane time constant of the axon were estimated to be 130 microns and 1 msec, respectively. The threshold amplitude of movement required to produce action potentials was also measured as a function of frequency. It gave a power law relationship which was exactly the inverse of the frequency response of the receptor during strong stimulation and rapid firing. This suggests that adaptation of the sensory discharge in this receptor is produced by the action potential encoding mechanism.
Glucocorticoids stimulate adrenergic differentiation in cultures of migrating and premigratory neural crest
Authors: Smith J , Fauquet M
Published: March 2018

Glucocorticoid hormones stimulate catecholamine (CA) anabolism in a variety of adrenergic derivatives of the neural crest. We describe work performed to investigate the action of these steroids on the catecholaminergic differentiation of neural crest cells themselves. Crest was taken from the trunk level of 2-day quail embryos, before migration had begun, and was cultured in vitro. Adrenergic differentiation, characterized by the ability of the cultures to synthesize and store CA, was minimal and was not improved when glucocorticoids were added to the medium. In contrast, extensive adrenergic differentiation occurred when neural crest cells, removed from the embryo 24 hr later, toward the end of their migratory phase, were cultured with the sclerotomal component of the somite (their immediate embryonic microenvironment). This process was considerably stimulated by corticosteroids; the rate of conversion of [3H]tyrosine to intracellular CA (norepinephrine, epinephrine, and dopamine) was 2 to 3 times higher in cultures exposed for 7 days to 10(-6) to 10(-7) M hydrocortisone, corticosterone, or dexamethasone, and the diameter of the dense-core vesicles seen in cell bodies and processes after permanganate fixation was strikingly increased. The effect was specific for the adrenergic phenotype in that acetylcholine synthesis by the cultures was consistently unaffected by hormone treatment. We infer that glucocorticoids do not trigger adrenergic differentiation, but that they selectively enhance catecholaminergic properties in crest cells that have already been exposed to an appropriate signal of another kind. This conclusion is strengthened by the observation that glucocorticoids stimulated the development of CA-producing cells from premigratory crest grown in the presence of somites and notochord, postulated sources of factors initiating adrenergic differentiation in the embryo. Although the intervention of glucocorticoids in vivo at very early embryonic stages remains to be established, our results indicate that neural crest derivatives would be potentially responsive to these hormones as soon as the sympathetic ganglia form.
Growth-related order of the retinal fiber layer in goldfish
Authors: Easter SS , Bratton B , Scherer SS
Published: March 2018

The retinal fiber layer and the juxtaretinal portion of the optic nerve of goldfish have been studied with light and electron microscopy in order to determine whether the age-related order of fibers in the nerve originates in the retina. In the retina, no patent spaces (channels) were noted. The fibers ran in fascicles and consisted of two classes: nonmyelinated fibers, which ran superficially (close to the vitreal surface), and “myelinated” fibers, which ran more deeply and were loosely wrapped by processes presumed to be glial. The myelinated fibers were larger and presumably older. The nonmyelinated fibers are believed to be the young ones, from the peripheral, more recently generated, ganglion cells, for the following reasons. (1) Their size and cytoskeletal elements were typical of young axons. (2) They were the only axons in peripheral retina. (3) They were continuous with the nonmyelinated fibers in the nerve, previously shown to be the young ones. (4) When retinal axons were cut peripherally, the degenerating axons were in the superficial part of the fiber layer. (5) Growth cones, presumably from the newest ganglion cells, were always observed at the most superficial position in the fiber layer, in direct contact with the basal lamina of the inner limiting membrane superficially and nonmyelinated fibers deeply. The nonmyelinated fibers always clustered together in the retinal fiber layer and occupied the most central portion in the cross-section of the optic nerve head. Thus, the age- related organization of fibers in the nerve is established in the retina. These results are discussed in the context of growth, with the aim of evaluating the relative importance of four factors that might influence the intraretinal course of the growth cone. Its interactions with other fibers and with the basal lamina of the inner limiting membrane seem to be more important than interactions with the glial end feet or guidance into open, preformed channels.
Development of the topographical projection of motor neurons to a rat muscle accompanies loss of polyneuronal innervation
Authors: Bennett MR , Lavidis NA
Published: March 2018

The rat lateral gastrocnemius muscle receives a topographical projection from lumbar segmental nerves L4 and L5. A study has been made of the development of this projection during the period when polyneuronal innervation is eliminated. The tetanic contraction due to stimulation of each nerve was compared with that due to stimulation of both nerves simultaneously. This percentage of contraction declined from about 90% to 70% for L4 from birth to 2 postnatal weeks; it declined from about 90% to 30% for L5 over the same period. The innervation of about 60% of the cells by both L4 and L5 is therefore eliminated during 2 postnatal weeks. Tetanic and twitch contraction due to stimulation of ventral rootlets of segmental level L4 and L5 was compared to stimulation of the whole muscle directly. There was a general reduction in the size of the motor units from both L4 and L5. A selective reduction in the number of L5 motor units was observed during the first 5 postnatal days. The distribution of L4 and L5 terminals on the dorsal surface of the muscle was determined by intracellular impalement of muscle cells and was determined by recording endplate potentials (EPPs) due to stimulation of L4 and L5. Polyneuronal innervation of the lateral gastrocnemius is eliminated by about 2 postnatal weeks. The percentage of muscle cells innervated by L4 or L5 in each of six equal-size muscle sectors was ascertained during this period. This percentage of innervation of muscle cells by L5 declined in all sectors between 3 days and 2 weeks postnatal.(ABSTRACT TRUNCATED AT 250 WORDS)
Sexual behavior and aggression in male mice: involvement of the vomeronasal system
Authors: Clancy AN , Coquelin A , Macrides F , Gorski RA , Noble EP
Published: March 2018

Recent observations have implicated the vomeronasal (accessory olfactory) system in the chemosensory control of rodent social behaviors. The purpose of this study was to observe the effects of peripheral vomeronasal organ extirpation on sexual behavior, aggression, and urine marking in male mice. Relative to sham-operated control animals, mice lacking vomeronasal organs displayed significantly reduced levels of copulatory behavior and intermale aggression. Urine marking rates were not reduced. The peripheral removal of the vomeronasal organ resulted in complete bilateral deafferentation of the accessory olfactory bulbs but spared the peripheral input to the main olfactory bulbs as evidenced by the lack of anterograde vomeronasal nerve transport but normal anterograde olfactory nerve transport of intranasally applied horseradish peroxidase. Neither body weights, paired testes weights, nor seminal vesicle weights of mice with vomeronasal system lesions differed significantly from those of control animals. Thus, an intact vomeronasal organ is important for the normal display of sexual behavior and aggression in male mice, and the reductions in these androgen-dependent behaviors following peripheral deafferentation of the vomeronasal system cannot be attributed to a chronic reduction of gonadal hormone secretion.
Characterization of L-glutamic acid transport by glioma cells in culture: evidence for sodium-independent, chloride-dependent high affinity influx
Authors: Waniewski RA , Martin DL
Published: March 2018

The transport of radiolabeled L-glutamic acid by LRM55 glioma cells in culture was examined. Time course studies indicated that L-[3H]glutamic acid is rapidly accumulated, and then 3H is lost from the cell, presumably in the form of glutamate metabolites. Kinetic analysis of L- glutamate uptake provided evidence for two components of transport. A low affinity component was found to persist at 0 to 4 degrees C and was not saturable, influx being proportional to the substrate concentration. A high affinity component, resolved by subtraction of the influx at 0 to 4 degrees C, followed Michaelis-Menten kinetics having a Km of 123 microM and a Vmax of 2.99 nmol/min/mg of protein. The transport system was highly substrate-specific: At least 27-fold larger concentrations of the most potent analogues--cysteic acid, cysteine sulfinic acid, and L-aspartic acid--were required to compete effectively with glutamate. Second, the system was not severely affected by exposure to inhibitors of oxidative phosphorylation or gamma-glutamyltranspeptidase. Third, only 65% of the high affinity uptake was dependent upon the presence of sodium, the other 35% being dependent upon chloride. These observations were supported by the findings that uptake was only partially inhibited by ouabain and quite effectively reduced by several inhibitors of chloride transport. The results of this study provide information on the properties of low affinity glutamate transport, as well as the first description of sodium-independent, chloride-dependent high affinity glial transport. The high affinity component of influx is stimulated by elevated potassium and inhibited by several pharmacological agents. The sodium independence of a significant proportion of high affinity glutamate transport suggests that glutamate binding studies done in sodium-free medium with intact cells may be confounded by a considerable amount of intracellular uptake.
Transient and differential expression of aspects of the catecholaminergic phenotype during development of the fetal bowel of rats and mice
Authors: Gershon MD , Rothman TP , Joh TH , Teitelman GN
Published: March 2018

A population of proliferating cells in the fetal gut has previously been found to express transiently aspects of a catecholaminergic phenotype (TC cells) during development in both rats and mice. These cells appear to be noradrenergic in rats but dopaminergic in mice. In the current study, the ability of TC cells, identified by the immunocytochemical demonstration of tyrosine hydroxylase (TH), to take up and become radioautographically labeled by [3H]norepinephrine ([3H]NE) was assessed. When TC cells were most numerous in the bowel of rats, no cells were labeled by [3H]NE (days E12 and E13). In rats, but not mice, labeling of larger cell bodies by [3H]NE was found on days E14 and E15. However, no cells showed TH immunoreactivity on day E15, although a few cells were doubly labeled by [3H]NE and TH immunoreactivity on day E14. Therefore, in rats TC cells contain TH immunoreactivity but do not take up [3H]NE prior to day E14, and their disappearance is followed by the appearance of a second population of larger cells that lacks TH immunoreactivity but which does take up [3H]NE. The transient appearance of some cells that express both markers on day E14 suggests, but does not prove, that TC cells change their phenotype and are the precursors of the cells found later in development that lack TH but which take up [3H]NE. The cells that take up [3H]NE are rare or absent in newborn rat gut, indicating that they may also be transient. These results indicate that genes responsible for different aspects of the noradrenergic phenotype need not necessarily be coupled in their expression. Although uptake of [3H] NE into cell bodies was not found on day E13 or later in vivo in mouse gut, it does occur in mouse bowel explanted prior to day E13 and grown for 10 to 12 days in culture. These cultures also contained TH immunoreactive cells. Thus, the potential for development of cells able to take up [3H]NE exists in mice as well as in rats, and the conditions that lead to a loss of catecholaminergic traits in vivo do not exist in vitro.
Characterization and localization of adenosine receptors in rat spinal cord
Authors: Geiger JD , LaBella FS , Nagy JI
Published: March 2018

Adenosine A1 receptors were characterized in membranes from rat dorsal and ventral spinal cord using [3H] cyclohexyladenosine [( 3H]CHA) and compared with those in brain. For determination of anatomical loci of adenosine A1 receptors in the dorsal and ventral spinal cord, various lesions were employed, including kainic acid injections directly into the lumbar dorsal spinal cord, spinal cord hemitransections, dorsal rhizotomies, and neonatal capsaicin treatment. In control animals a single high affinity binding component was observed in dorsal and ventral spinal cord with KD values of 2.3 and 2.6 nM and Bmax values of 170 and 123 fmol/mg of protein, respectively. In comparison, [3H]CHA binding to whole brain membranes exhibited KD and Bmax values of 2.3 nM and 301 fmol/mg of protein, respectively. The IC50 values for CHA, (-)- phenylisopropyl adenosine, adenosine-5′-ethylcarboxamide, 2- chloroadenosine, (+)-phenylisopropyl adenosine, and theophylline to displace [3H]CHA were 3.6, 2.3, 15, 17, 21, and 30,500 nM for dorsal horn and 5.1, 2.7, 9.8, 24, 25, and 21,000 nM for ventral horn. The potencies of the various ligands are similar to those found for brain tissue. Injection of kainic acid directly into the dorsal spinal cord significantly reduced specific [3H]CHA binding by 33% in this tissue when compared to values from saline-injected control animals. This decrease was accompanied histologically by the depletion of intrinsic neuronal cell bodies and extensive gliosis at the injection site. Terminals of descending or primary afferent systems appear not to contain [3H]CHA-binding sites since lesions which interrupt these systems failed to alter the levels of [3H]CHA receptors in denervated spinal cord tissue.(ABSTRACT TRUNCATED AT 250 WORDS)
Pathfinding by neuronal growth cones in grasshopper embryos. III. Selective affinity of the G growth cone for the P cells within the A/P fascicle
Authors: Bastiani MJ , Raper JA , Goodman CS
Published: March 2018

The growth cone of the G neuron selectively fasciculates upon specific axon bundles in a stereotypic sequence as it navigates through the developing central nervous system of the grasshopper embryo. It turns and extends anteriorly in the contralateral neuropil of the second thoracic ganglion at a specific choice point where it fasciculates with the A/P axon bundle which contains the axons of the A1, A2, P1, and P2 neurons. We previously hypothesized (Raper, J. A., M. J. Bastiani, and C. S. Goodman (1983) J. Neurosci. 3: 20–41) that this fascicle, or subsets of axons within it, were specifically labeled and that the G neuron was determined to follow this labeled pathway. Here we report on an ultrastructural analysis of the interactions between the G growth cone and its filopodia with the cells of the A/P fascicle at the choice point. As G reaches its choice point, its filopodia are in more frequent contact with the A/P fascicle in comparison to the other longitudinal axon fascicles. Within the A/P fascicle, the tip of G's growth cone is found to be closely associated with the P and not the A axons. Furthermore, before the G growth cone climbs onto the A/P fascicle, its filopodia show a selective affinity for the P axons as compared to the A axons. Another specific interaction involves selective filopodial insertions; only filopodia from the P cells were found to insert into the G growth cone and induce coated pits and vesicles. These findings suggest that G is able to distinguish the A/P fascicle from other axon bundles and, moreover, is able to distinguish the P axons from the A axons. The companion paper (Raper, J. A., M. J. Bastiani, and C. S. Goodman (1984) J. Neurosci. 4: 2329–2345) presents experimental results based on specific axon ablations that further support this hypothesis.
Pathfinding by neuronal growth cones in grasshopper embryos. IV. The effects of ablating the A and P axons upon the behavior of the G growth cone
Authors: Raper JA , Bastiani MJ , Goodman CS
Published: March 2018

In the companion paper (Bastiani, M. J., J. A. Raper, and C. S. Goodman (1984) J. Neurosci. 4: 2311–2328), we show that as the G growth cone reaches its choice point and turns anteriorly on the A/P fascicle, its filopodia demonstrate selective affinity for the A/P fascicle as compared to the other approximately 25 longitudinal axon fascicles, and within the A/P fascicle itself, G's filopodia selectively contact the P axons as compared to the A axons. These results support the hypothesis that the A/P fascicle, and, moreover, subsets of axons within it (Ps versus As), are specifically labeled and that the G growth cone is determined to follow a particular labeled pathway. We tested the “labeled pathways” hypothesis by specifically ablating these axons and examining the subsequent behavior of the G growth cone in embryos grown in culture. Ablation of the A and P axons prevents G from growing more than a short distance anteriorly, although the G growth cone is within grasp of many other longitudinal axon fascicles. Ablation of only the P axons has a similar effect; the G growth cone behaves normally if only the A axons are ablated. Transmission electron micrograph semiserial section reconstructions of experimental embryos further indicate that G's growth cone behaves abnormally when the A and P axons, or only the P axons, are ablated. The G growth cone branches extensively in the lateral and ventral neuropil without it or its filopodia showing a high affinity for any other axon fascicle. These results indicate that the G growth cone is able to distinguish the A/P fascicle from the other longitudinal axon fascicles in the developing neuropil. Moreover, the results suggest that within the A/P fascicle the G growth cone is able to distinguish the P axons from the A axons.
Monosynaptic inhibition of phrenic motoneurons: a long descending projection from Botzinger neurons
Authors: Merrill EG , Fedorko L
Published: March 2018

Synaptic connections between medullary expiratory neurons and phrenic motoneurons were studied in anesthetized cats using spike-triggered averaging of synaptic noise in phrenic motoneurons. Monosynaptic inhibition of phrenic motoneurons originating from the rostral medullary expiratory neurons of the Botzinger complex was revealed. Neither mono- nor disynaptic inhibition from expiratory neurons of the nucleus retroambigualis was found. It was concluded that Botzinger complex expiratory neurons make long descending inhibitory connections with phrenic motoneurons: the expiratory neurons of the nucleus retroambigualis do not appear to make synaptic connections with phrenic motoneurons.
Alterations in neural cell adhesion molecules during development of different regions of the nervous system
Authors: Chuong CM , Edelman GM
Published: March 2018

Several cell adhesion molecules involved in neuron-neuron and neuron- glia interactions have been identified in our laboratory and have been shown to undergo cell surface modulation. In the case of the neural cell adhesion molecule (N-CAM), it has been found that during development the molecule is converted from a microheterogeneous embryonic (E) form containing 30 gm of sialic acid/100 gm of polypeptide to several distinct adult (A) forms containing one third as much of this sugar. In vitro analyses indicate that this change is accompanied by a 4-fold increase in the rate of N-CAM homophilic binding. In the present study of the mouse and the chick, alterations of N-CAMs occurring as a result of E----A conversion, prevalence modulation, and changes in antigenic state during the development of different neural regions were analyzed by the use of highly specific polyclonal and monoclonal antibodies combined with anatomical dissection and several new quantitative assays. We made the following observations. The relative concentration of N-CAM changed during development, with the highest concentration (2.8 times the adult level) occurring around the perinatal period. Each brain region followed a similar pattern of change but according to a different time schedule. While conversion from the E to the A forms of N-CAM occurred mainly during the first 3 postnatal weeks in mice, the relative conversion rates were distinctly different in various neural tissues. The extreme examples are dorsal root ganglia, which already displayed the A forms at birth, and the diencephalon and tectal region, which still retained some E forms in the adult. A cephalocaudal maturation gradient of E---- A conversion was observed in the spinal cord and dorsal root ganglia. Differences in the antigenic determinants of N-CAMs from different neural tissues were detected by two independent monoclonal antibodies. Finally, in some adult neural tissues, one of the three A forms was found to be dominant. These results establish that during development there are definite quantitative and qualitative differences among N- CAMs from various neural tissues. The data are consistent with the hypothesis that alterations in the relative amounts and forms of N-CAM play major roles in neural morphogenesis, possibly by altering the rates of adhesion among neurons and their processes.
Effect of dopamine system activation on substantia nigra pars reticulata output neurons: variable single-unit responses in normal rats and inhibition in 6-hydroxydopamine-lesioned rats
Authors: Waszczak BL , Lee EK , Tamminga CA , Walters JR
Published: March 2018

Previous single-unit recording studies have revealed that randomly selected pars reticulata neurons respond in a highly variable and complex fashion to intravenous administration of the dopamine agonist, apomorphine. The current studies were undertaken (1) to assess whether the variable pattern of responses of reticulata neurons to intravenous apomorphine correlates with their sites of projection and (2) to determine how reticulata responses to apomorphine might be altered by the presence of striatal dopaminergic supersensitivity. Extracellular, single-unit recording studies were conducted in anesthetized, paralyzed rats. Pars reticulata neurons were identified by antidromic activation from either the ventromedial nucleus of the thalamus or superior colliculus. Neurons of both subpopulations exhibited similar, highly variable changes in firing rate during the 10-min period immediately following intravenous injection of 320 micrograms/kg of apomorphine, a dose of the drug considered sufficient to stimulate striatal postsynaptic dopamine receptors. These responses, which were not qualitatively different from those previously observed among reticulata cells not distinguished on the basis of projection site, could be reversed by subsequent administration of dopamine antagonist drugs. In contrast to the variable responses in normal animals, the same dose of apomorphine caused a rapid and usually total inhibition of pars reticulata cell firing in rats which received 6-hydroxydopamine lesions of the nigrostriatal dopamine pathway 6 to 8 weeks prior to recording experiments. These inhibitions of firing could also be reversed by administration of dopamine antagonists.(ABSTRACT TRUNCATED AT 250 WORDS)
Reciprocal modulation of agonist and antagonist binding to inhibitory adenosine receptors by 5'-guanylylimidodiphosphate and monovalent cations
Authors: Green RD
Published: March 2018

Previous work from this laboratory showed that rat hippocampal membranes contain adenosine receptors that mediate GTP-dependent inhibition of adenylate cyclase activity (Yeung, S. -M. H., and R. D. Green (1983) J. Biol. Chem. 258: 2334–2339). Furthermore, we reported that guanine nucleotides decrease agonist and increase antagonist binding to these adenosine receptors. The present study examines the effects of monovalent cations and guanine nucleotides, alone and in combination, on the binding of agonist [( 3H]N6(L- phenylisopropyl)adenosine) and antagonist [( 3H]diethylphenylxanthine) radioligands to adenosine receptors in rat hippocampal membranes. Low concentrations of monovalent cations (less than or equal to 100 mM) did not affect agonist binding. 5′-Guanylylimidodiphosphate (Gpp(NH)p) alone increased the KD of the agonist without affecting the maximal number of sites labeled by the agonist (Bmax); in the presence of monovalent cations, Gpp(NH)p both increased the KD and decreased the number of sites labeled by the agonist. In contradistinction, Gpp(NH)p increased the maximal number of sites to which the antagonist bound without affecting its KD, while monovalent cations decreased the KD of the antagonist both in the absence and the presence of Gpp(NH)p. It is proposed that both agonist and antagonist-receptor complexes exist in three distinct affinity states and that the transitions between these states are modulated by guanine nucleotides and monovalent cations.(ABSTRACT TRUNCATED AT 250 WORDS)
Decrease of gap junction permeability induced by dopamine and cyclic adenosine 3':5'-monophosphate in horizontal cells of turtle retina
Authors: Piccolino M , Neyton J , Gerschenfeld HM
Published: March 2018

The axon terminals of the H1 horizontal cells of the turtle retina are electrically coupled by extensive gap junctions. Dopamine (10 nM to 10 microM) induces a narrowing of the receptive field profile of the H1 horizontal cell axon terminals, increases the coupling resistance between them, and decreases the diffusion of the dye Lucifer Yellow in the network formed by the coupled axon terminals. These actions of dopamine involve the activation of D1 receptors located on the membrane of the H1 horizontal cell axon terminals proper. Increases of the intracellular cyclic AMP concentration induced by either stimulating the adenylate cyclase activity with forskolin or inhibiting the phosphodiesterase activity with isobutylmethylxanthine, theophylline, aminophylline, or compound RO 20-1724 elicit effects similar to those of dopamine on the receptive field profile of the H1 horizontal cell axon terminals, on their coupling resistance, and on the diffusion of Lucifer Yellow in the axon terminal network. It is concluded that dopamine decreases the permeability of the gap junctions between the axon terminals of the H1 horizontal cells of the turtle retina and that this action probably involves cyclic AMP as a second messenger.
Stimulation of protein synthesis and glucose utilization in the hypoglossal nucleus induced by axotomy
Authors: Smith CB , Crane AM , Kadekaro M , Agranoff BW , Sokoloff L
Published: March 2018

The metabolic responses of rat hypoglossal nuclei to unilateral section of the 12th cranial nerve have been studied. Changes in the rates of protein synthesis and glucose utilization in the regenerating nucleus were determined with two quantitative autoradiographic techniques, the L-[1–14C]leucine method and the [14C] deoxyglucose method, respectively. The results show that both of these processes increase in the nucleus ipsilateral to the sectioned nerve and are unaffected in the contralateral nucleus as compared with sham-operated animals. The time courses of these metabolic changes have been compared with that of the return of functional innervation of the tongue. An increase in glucose utilization is first detected 24 hr postaxotomy. It is maximal between 1 and 3 days postaxotomy and constitutes an 84% increase over the rate in the contralateral control nucleus. The increase in protein synthesis is of smaller magnitude than that of glucose utilization. It is maximal at 48 hr after axotomy and constitutes a 25% increase over the rate in the contralateral nucleus. The increases in both of these metabolic processes persist even after functional recovery of the tongue at 21 days postaxotomy. Protein synthesis and glucose utilization return to normal levels between 24 and 35 days postaxotomy. Although the time courses of the changes in protein synthesis and glucose utilization are similar, the magnitude of the increase in glucose utilization is too large to be accounted for by the energy requirements of the relatively small increase in protein synthesis and probably reflects other processes as well, including altered function of the soma-dendritic membrane of regenerating neurons.
Differential emergence of cellular mechanisms mediating habituation and sensitization in the developing Aplysia nervous system
Authors: Rayport SG , Camardo JS
Published: March 2018

The development of the cellular substrates underlying habituation and sensitization, two simple forms of learning, was examined at a polysynaptic sensory-to-motor connection in the neural circuit mediating defensive mucus release in the marine mollusc, Aplysia californica. Animals were studied throughout juvenile life, stages 9 (40 days of development) to 12 (95 days), and into adulthood, stage 13 (120 days), starting just after metamorphosis when mucus release first becomes evident. Homosynaptic depression, which mediates habituation, was already present in its adult form in stage 9. Heterosynaptic facilitation, which mediates sensitization, appeared in stage 10 and reached maturity during stages 11 and 12. Thus, the development of synaptic plasticity in this circuit occurs in discrete phases in which the gradual emergence of heterosynaptic facilitation occurs only after homosynaptic depression is well established.
Receptor autoradiography in thoracic spinal cord: correlation of neurotransmitter binding sites with sympathoadrenal neurons
Authors: Seybold VS , Elde RP
Published: March 2018

Receptor autoradiography was combined with the retrograde labeling of sympathoadrenal neurons by fast blue to determine whether opiate, serotonin, catecholamine, or cholinergic binding sites could be spatially correlated with preganglionic neurons in the rat intermediolateral cell column (IML) that project to the adrenal gland. [3H]Dihydromorphine (DHM) was used for the visualization of mu opiate receptors, [3H]lysergic acid diethylamide (LSD) for serotonin receptors, [3H]para-aminoclonidine (pAC) for alpha 2-adrenergic receptors, and [3H]quinuclidinyl benzilate (QNB) for muscarinic cholinergic receptors. While qualitative assessment of autoradiograms indicated that alpha 2-adrenergic and muscarinic receptors were concentrated in the intermediate zone of the spinal cord, quantitation of grains in specific regions of the intermediate gray revealed that alpha 2-adrenergic and serotonergic receptors were more highly concentrated over sympathoadrenal preganglionic neurons than over other regions in IML or the adjacent intermediate gray matter. Information concerning the distribution of neurotransmitter-binding sites in other regions of thoracic spinal cord was also obtained. All ligands showed relatively dense binding sites in the superficial laminae of the dorsal horn, and all but [3H]DHM revealed similar densities of binding sites in the region adjacent to the central canal. Only [3H]QNB revealed a high density of binding sites in the ventral horn of the spinal cord.
Emergence of cyclic guanosine 3':5'-monophosphate-dependent protein kinase immunoreactivity in developing rhesus monkey cerebellum: correlative immunocytochemical and electron microscopic analysis
Authors: Levitt P , Rakic P , De Camilli P , Greengard P
Published: March 2018

The appearance of cyclic guanosine 3′:5′-monophosphate-dependent protein kinase (cGK), an enzyme that may be involved in the regulation of various aspects of neuronal function and that is highly concentrated in cerebellar Purkinje cells, was studied in the developing and adult monkey cerebellum by indirect immunofluorescent staining. The appearance and distribution of cGK immunoreactivity were then correlated with the stages of Purkinje cell differentiation and with the establishment of synaptic inputs to Purkinje cells as revealed by electron microscopy and by the presence of synapsin I, a specific nerve terminal marker. In the adult monkey, in analogy with previous observations in the adult rat, cGK immunoreactivity was detected throughout the cytoplasm of all Purkinje cells and was not seen in other neurons. During ontogenesis, cGK immunoreactivity appeared for the first time in Purkinje cells at the 97th embryonic day (E97). On this day it was detectable in Purkinje cells situated in the posterior lobe concurrently with the emergence of synapsin I immunoreactivity surrounding their somata. The cGK-positive cells had entered the phase of rapid dendritic growth and had begun establishing axosomatic synapses. By E102, Purkinje cells in the posterior lobe and in most of the anterior lobe were cGK positive. By E125, all Purkinje cells had received synaptic contacts and had become cGK positive. In addition to typical Purkinje cells situated in the cortex, we found another population of cGK-positive neurons present transiently in the prospective cerebellar white matter. These neurons, which were observed only during the second half of gestation, had morphological similarities to Purkinje cells. The emergence of cGK in these neurons also coincided with their dendritic proliferation and with the appearance of synapsin I immunoreactivity around their cell bodies. Subcortical cGK-positive cells were not observed in postnatal animals. Such neurons may be Purkinje cells which, failing to reach the cortical plate, subsequently degenerate. The close temporal correlation between appearance of cGK immunoreactivity, onset of synaptic inputs, and dendritic proliferation, both in typical Purkinje cells and in the Purkinje cell-like cells in subcortical areas, suggests that expression of high levels of cGK may be an important aspect of the neuronal differentiation of these cells.
Antibodies to synthetic peptides defined by cDNA cloning reveal a network of peptidergic neurons in Aplysia
Authors: Kreiner T , Rothbard JB , Schoolnik GK , Scheller RH
Published: March 2018

We previously isolated and characterized a cDNA clone specifically expressed in neurons R3 to R8 and R14 of the Aplysia abdominal ganglion (Nambu, J.R., R. Taussig, A.C. Mahon, and R.H. Scheller (1983) Cell 35: 47–56). The cDNA nucleotide sequence and the inferred protein amino acid sequence suggest that this gene encodes the precursor for neuroactive peptides used by these cells. Peptides corresponding to three regions of the precursor were synthesized, coupled to a protein carrier, and used to generate antibodies. These antibodies stain a set of cell bodies, R3 to R14, and their processes in the abdominal ganglion; no other cells in the nervous system or the periphery are immunoreactive. R3 to R14 send numerous fine immunoreactive processes into the vascularized sheath that surrounds the ganglion. Each of these cells also has a large axon which exits the ganglion via the branchial nerve and terminates on the heart. In addition, R14 is anatomically distinct from R3 to R13 in that it sends additional immunoreactive processes to the vasculature near the ganglion. Immunoreactive processes and varicosities were observed on the efferent vein of the gill, the abdominal ganglion artery, and the anterior aorta. These data are consistent with previous studies suggesting that one or more neuropeptides released from R3 to R14 function as modulators of cardiovascular physiology.
A neural code for auditory space in the cat's superior colliculus
Authors: Middlebrooks JC , Knudsen EI
Published: March 2018

We have examined the intermediate and deep layers of the cat's superior colliculus for evidence of a neural representation of auditory space. We measured the responses of single units to sounds presented in a free field. The results support the following generalizations. Most auditory units in the superior colliculus have sharply delimited receptive fields which form two discrete classes distinguished by their locations and sizes. The remaining units respond to sounds presented at any location. Each auditory unit responds maximally to sounds at a particular horizontal and vertical location within its receptive field, the unit's “best area.” The best areas and receptive field borders of a unit are resistant to changes in the intensity of stimulus. The locations of best areas shift systematically as a function of unit position to form a continuous map of auditory space. The horizontal dimension of space is mapped rostrocaudally, and the vertical dimension is mapped mediolaterally. This map corresponds in orientation with the map of visual space. These data permit us to infer the distribution of unit activity elicited by a sound at any given location. Regardless of its location, a sound activates a substantial portion of the superior colliculus. Indeed, sounds at some locations activate nearly all of the auditory units. However the activated portion of the colliculus contains a restricted region of units which are excited to near their maximum firing rates. The position of this focus of greatest activity varies systematically according to the location of the sound source, thus mapping the location of the sound in space.
The glutamate analogue alpha-aminoadipic acid is taken up by astrocytes before exerting its gliotoxic effect in vitro
Authors: Huck S , Grass F , Hortnagl H
Published: March 2018

DL- and L-alpha-aminoadipic acid (alpha-AA) are specific gliotoxins in vitro (Huck, S., F. Grass, and M. E. Hatten (1984) Neuroscience 12: 783– 796). By combining immunohistochemical and autoradiographic techniques, we now show that DL-[14C]-alpha-AA is accumulated almost selectively by astrocytes in cultures of the dissociated postnatal mouse cerebellum, presumptive neurons being free of the radiolabel. High pressure liquid chromatography analysis of cultures incubated with D- or L-alpha-AA and DL-[14C]-alpha-AA autoradiograms conducted in the presence of D- or L- alpha-AA reveal a stereospecificity of astroglial L-alpha-AA uptake. Both the uptake of alpha-AA by astrocytes and alpha-AA-induced gliotoxicity were sodium dependent. Since 2 microM tetrodotoxin did not prevent the morphological changes, we conclude that sodium plays its role in alpha-AA-induced gliotoxicity by mediating the transport of the substance. Thus, alpha-AA appears to be taken up by the astrocytes before exerting its cytotoxic effect.
Postnatal development of laminar innervation patterns by monoaminergic fibers in monkey (Macaca fascicularis) primary visual cortex
Authors: Foote SL , Morrison JH
Published: March 2018

Immunohistochemical methods are used to characterize the distribution of noradrenergic and serotonergic fibers in primary visual cortex of cynomolgus monkeys (Macaca fascicularis) at various postnatal ages. Previous studies in adult squirrel monkeys have shown that serotonergic fibers are generally restricted to the upper four cortical laminae and are especially dense in layer IV, whereas noradrenergic fibers are especially dense in layers V and VI, moderate in layers I, II, and III, and virtually absent in layer IV (Morrison, J. H., S. L. Foote, M. E. Molliver, F. E. Bloom, and H. G. W. Lidov (1982) Proc. Natl. Acad. Sci. U.S.A. 2401–2405; Morrison, J. H., S. L. Foote, D. O'Connor, and F. E. Bloom (1982) Brain Res. Bull. 9: 309–319). Since these monoamines, especially norepinephrine, have been hypothesized to play an essential role in the developmental plasticity of visual cortex organization (e.g., Kasamatsu, T., and J. D. Pettigrew (1976) Science 194: 206–209; Pettigrew, J. D., and T. Kasamatsu (1978) Nature 271: 761–763), the present study examined the postnatal development of these innervation patterns, especially just before and just after the reported “critical period” for visual plasticity. A dense serotonergic innervation of layer IV is present at birth along with sparse innervation of other laminae. The adult pattern of serotonergic innervation, which is similar to that in the squirrel monkey but even more specifically laminated, becomes evident by 6 weeks of age. In the adult pattern, the most dense innervation remains in layers IVb and IVc. A much lower density of noradrenergic than of serotonergic fibers is evident at all ages examined. As with serotonin, the lowest density of fibers is observed at birth. By about 2 months of age these noradrenergic fibers have become more dense, and their laminar distribution is similar to that of adult cynomolgus which is similar to adult squirrel monkey. These studies indicate that: (1) both types of innervation display a continuum of development, with no abrupt changes, (2) serotonergic innervation is more dense than noradrenergic innervation at every age examined, (3) these two transmitter systems exhibit very different laminar innervation patterns as early as birth, and (4) the greater laminar specialization of area 17 in cynomolgus versus squirrel monkeys is accompanied by corresponding enhanced laminar specialization of these monoaminergic afferents.
Posture control and trajectory formation during arm movement
Authors: Bizzi E , Accornero N , Chapple W , Hogan N
Published: March 2018

One hypothesis for the generation of spatially oriented arm movements by the central nervous system is that a desired joint position is determined by the ratio of the tensions of agonist and antagonist muscles. According to this hypothesis, the transition between equilibrium states should be solely a function of the contraction time of the motor units and the mechanical properties of the arm. We tested this hypothesis in intact and deafferented rhesus monkeys by holding the forearm and measuring the accelerative transient after release of the forearm and by directly measuring the time course of the increase in torque during the movement. Both methods indicated an average time of 400 msec for attaining peak torque in a movement with a duration of 700 msec. In addition, by displacing the arm from its normal trajectory during the movement, we observed that the arm returned neither to the initial nor to the final equilibrium positions, but to points intermediate between them. We conclude that the processes underlying trajectory formation must be more complex than a simple switch between one equilibrium position and another.
Modification of guanine nucleotide-regulatory components in brain membranes. I. Changes in guanosine 5'-triphosphate regulation of opiate receptor-binding sites
Authors: Lambert SM , Childers SR
Published: March 2018

Guanine nucleotides regulate binding of opiate agonists to membrane receptors by increasing agonist dissociation rates. The current study demonstrates that the ability of guanosine 5′-triphosphate (GTP) and its nonhydrolyzable analogue guanylyl-5′-imidodiphosphate (Gpp(NH)p) to inhibit opiate agonist binding to rat brain membranes can be altered by two methods: by preincubating with EDTA, and by preincubating at pH 4.5. EDTA pretreatment increased the potency of Gpp(NH)p in inhibiting [3H]morphine binding by 4-fold, with little apparent change in the maximum effect of Gpp(NH)p or on levels of binding itself. The effect of EDTA pretreatment was blocked by prior incubation of membranes with excess calcium or manganese but could not be reversed by any divalent cation if the EDTA incubation was longer than 10 min. EDTA pretreatment increased the effects of GTP on dissociation rates of agonists. Pretreatment of membranes at pH 4.5 increased the ability of guanine nucleotides to regulate agonist binding by increasing the maximum effect of Gpp(NH)p from 50% to 80% inhibition of [3H]morphine binding with minor increase in potency of Gpp(NH)p. The actions of EDTA and low pH pretreatments were additive when both were conducted on the same membranes. These results suggest that modification of brain membranes can alter the interaction of receptors with guanine nucleotide- regulatory components which may lead to changes in post-receptor membrane events.
Modification of guanine nucleotide-regulatory components in brain membranes. II. Relationship of guanosine 5'-triphosphate effects on opiate receptor binding and coupling receptors with adenylate cyclase
Authors: Childers SR , LaRiviere G
Published: March 2018

Guanine nucleotides couple receptors to stimulate or inhibit adenylate cyclase as well as regulate binding of neurotransmitters. To explore the relationship between these different functions of guanosine 5′- triphosphate (GTP), rat brain membranes were preincubated in 50 mM sodium acetate, pH 4.5, which increased GTP regulation of 3H-opiate agonist binding. Assay of adenylate cyclase in the low pH-pretreated membranes revealed no loss of basal activity but a dramatic loss in fluoride- and guanylyl-5′-imidodiphosphate-stimulated activity, thus suggesting a loss in stimulatory guanine nucleotide coupling function. Manganese stimulation, which presumably occurs on the catalytic subunit of adenylate cyclase directly, was not affected by low pH treatment. In striatum, dopamine-stimulated adenylate cyclase was eliminated, but inhibition of adenylate cyclase by D-Ala2-Met5-enkephalinamide (D-Ala enk) was increased by low pH treatment. The effect of low pH on sodium fluoride-stimulated and D-Ala enk-inhibited adenylate cyclase could be reversed by addition of either cis-vaccenic acid or phosphatidylcholine to treated membranes, but the effect on GTP regulation of binding was not reversed by lipid incorporation. These results suggest that fundamental differences exist between membrane components which couple receptors to adenylate cyclase and those that regulate neurotransmitter binding.