bluuebunny/crossref_metadata_2025 huggingface dataset:
Adaptive plasticity in the primate spinal stretch reflex: evidence for a two-phase process
Authors: Wolpaw JR , O'Keefe JA
Published: March 2018

Monkeys can slowly increase or decrease the amplitude of the purely spinal, largely monosynaptic portion of the response to sudden muscle stretch, the spinal stretch reflex (SSR), when confronted by a task requiring such change (Wolpaw, J.R., V.A. Kieffer, R.F. Seegal, D.J. Braitman, and M.G. Sanders (1983) Brain Res. 267: 196–200; Wolpaw, J.R., D.J. Braitman, and R.F. Seegal (1983) J. Neurophysiol. 50: 1296– 1311). Change occurs without alteration in initial muscle length or in background activity of agonist, antagonist, or synergist muscles. This study uses composite curves to describe in detail the development of SSR amplitude change. It reveals important, previously unexpected features of this development. SSR increase or decrease appears to occur in two distinct phases. Phase I, a nearly immediate 8% change, occurs within the first 6 hr. Phase II, a 2%/day change, continues for at least 2 months. Although phase II is much slower than phase I, its final magnitude is far greater. Phase I indicates a nearly immediate change in suprasegmental influence of the segmental arc of the SSR. Because stretch onset time is unpredictable and the SSR occurs before any other possible response, this change in descending activity must be tonic; it must be present continually, day after day, for the 5 to 7 hr/day the animal spends at the task. Phase I produces a rapid and significant increase in reward probability. Thus, it may be readily interpreted as an example of operant conditioning, provoked by the reward contingency.(ABSTRACT TRUNCATED AT 250 WORDS)
An organizing principle for a class of voluntary movements
Authors: Hogan N
Published: March 2018

This paper presents a mathematical model which predicts both the major qualitative features and, within experimental error, the quantitative details of a class of perturbed and unperturbed large-amplitude, voluntary movements performed at intermediate speed by primates. A feature of the mathematical model is that a concise description of the behavioral organization of the movement has been formulated which is separate and distinct from the description of the dynamics of movement execution. Based on observations of voluntary movements in primates, the organization has been described as though the goal were to make the smoothest movement possible under the circumstances, i.e., to minimize the accelerative transients. This has been formalized by using dynamic optimization theory to determine the movement which minimizes the rate of change of acceleration (jerk) of the limb. Based on observations of muscle mechanics, the concept of a “virtual position” determined by the active states of the muscles is rigorously defined as one of the mechanical consequences of the neural commands to the muscles. This provides insight into the mechanics of perturbed and unperturbed movements and is a useful aid in the separation of the descriptions of movement organization and movement execution.
Regional changes in brain glucose metabolism reflect cognitive impairments in aged rats
Authors: Gage FH , Kelly PA , Bjorklund A
Published: March 2018

Aged rats (22 to 24 months) and young control rats (3 months) were tested in a battery of behavioral tests which included tests of learning, place navigation, sensorimotor integration, motor coordination, activity, and exploration. Following testing all animals were analyzed in an unanesthetized state for their local glucose utilization. Significant differences in glucose utilization were found between the aged and young groups on some behaviors and in some brain regions. There was considerable variability in the aged group in both their behavioral performance and their glucose utilization scores; thus, attempts were made to determine whether the variability in the degree of impairment within any particular behavioral test was correlated to the regional glucose utilization scores in any of the 45 brain regions analyzed. In two of the behavioral tests employed (i.e., one for learning and one for place navigation), the decline in performance correlated significantly with the decrement in regional glucose utilization. Moreover, the performance in these two tests showed significant correlation with glucose use in only five regions (dentate gyrus, medial septum-diagonal band area, hippocampal CA1, hippocampal CA3, and prefrontal cortex). These results show that the learning impairments in the aged rats are related to the extent of decrease in glucose utilization in restricted areas of the limbic system. In addition, the results show that the individual rats within an aged rat population develop cognitive impairments to a variable degree and that the aged rats with the most pronounced learning impairments are the ones exhibiting the most severe functional decrements, in terms of glucose utilization, in the septohippocampal system and the prefrontal cortex. This suggests that aging rats may be interesting not only for the study of the normal aging process, but also as a model of dementia.
Naloxone increases electrophysiological measures of selective information processing in humans
Authors: Arnsten AF , Neville HJ , Hillyard SA , Janowsky DS , Segal DS
Published: March 2018

The effects of the opiate antagonist naloxone on electrophysiological measures of human selective attention were examined utilizing a paradigm which dissociates selective information processing from any concurrent processes of general arousal that may be present. Subjects were injected with naloxone (2 mg, i.v.) or placebo prior to performing a three-channel selective listening task. The measure of selective attention was the difference between the auditory event-related potential (AERP) to a sequence of tones when they were attended and to the same sequence of tones when they were ignored. Typically, the AERP to attended channel tones is more negative, and this increased negativity is designated the attention effect. In this study, naloxone produced a significant augmentation of the AERP attention effect at frontal electrode sites, primarily by decreasing the negativity of AERPs to inattended tones. Naloxone had no effect on the AERPs from the undistracted and divided attention tasks or on the sensitivity of the AERP to a physical parameter of stimulus presentation, interstimulus interval. The effects of naloxone on selective attention appear to be independent of any alterations in arousal, as the drug had no effect on autonomic measures, reaction times, or auditory sensitivity, and the attention changes could be dissociated from any naloxone-induced alterations of mood. These data indicate that naloxone can have the specific effect of increasing AERP measures of selective information processing, thus suggesting a role for endogenous opioid peptides in the regulation of auditory selective attention in humans.
Microcircuitry of bipolar cells in cat retina
Authors: McGuire BA , Stevens JK , Sterling P
Published: March 2018

We have studied 15 bipolar neurons from a small patch (14 X 120 micron) of adult cat retina located within the area centralis. From electron micrographs of 189 serial ultrathin sections, the axon of each bipolar cell was substantially reconstructed with its synaptic inputs and outputs by means of a computer-controlled reconstruction system. Based on differences in stratification, cytology, and synaptic connections, we identified eight different cell types among the group of 15 neurons: one type of rod bipolar and seven types of cone bipolar neurons. These types correspond to those identified by the Golgi method and by intracellular recording. Those bipolar cell types for which we reconstructed three or four examples were extremely regular in form, size, and cytology, and also in the quantitative details of their synaptic connections. They appeared quite as specific in these respects as invertebrate “identified” neurons. The synaptic patterns observed for each type of bipolar neuron were complex but may be summarized as follows: the rod bipolar axon ended in sublamina b of the inner plexiform layer and provided major input to the AII amacrine cell. The axons of three types of cone bipolar cells also terminated in sublamina b and provided contacts to dendrites of on-beta and other ganglion cells. All three types, but especially the Cb1, received gap junction contacts from the AII amacrine cell. Axons of four types of cone bipolar cells terminated in sublamina a of the inner plexiform layer and contacted dendrites of off-beta and other ganglion cells. One of these cone bipolar cell types, CBa1, made reciprocal chemical contacts with the lobular appendage of the AII amacrine cell. These results show that the pattern of cone bipolar cell input to beta (X) and probably alpha (Y) ganglion cells is substantially more complex than had been suspected. At least two types of cone bipolar contribute to each type of ganglion cell where only a single type had been anticipated. In addition, many of the cone bipolar cell pathways in the inner plexiform layer are available to the rod system, since at least four types of cone bipolar receive electrical or chemical inputs from the AII amacrine cell. This may help to explain why, in a retina where rods far outnumber the cones, there should be so many types of cone bipolar cells.
Perturbation of the direction of neurite growth by pulsed and focal electric fields
Authors: Patel NB , Poo MM
Published: March 2018

We have studied the orientation of neurite growth in the culture of embryonic Xenopus neurons in response to three types of extracellular electric fields: spatially uniform pulsed fields, focally applied steady (DC) fields, and focally applied pulsed fields. Under uniform pulsed fields, neurites showed a preferential orientation toward the cathode pole of the field in a manner similar to that previously found for DC fields. The extent of neurite orientation depended upon the duration, amplitude, and frequency of the pulse but appeared to be similar to that produced by a uniform DC field of an equivalent time- averaged field intensity. For square pulses of 5 msec duration, the minimal amplitude and frequency required to produce a detectable orientation of neurite growth over a period of 24 hr were 2.5 V/cm and 10 Hz, which correspond to a time-averaged field intensity of 125 mV/cm. Steady or pulsed focal fields were applied by passing a current through a micropipette placed near the growth cone of the neurite. Fields of negative polarity (current sink) were found to attract the growth cone, whereas fields of positive polarity (current source) were found to deflect the growth cone away from the pipette. The threshold DC current density needed at the growth cone to perturb its direction of growth within 15 min was 0.2 to 2 pA/micron2 (or 3 to 30 mV/cm); and for focal pulsed currents (pulse duration 5 msec), a typical combination of minimal pulse amplitude and frequency was 4 pA/micron2 and 10 Hz. This threshold focal current is similar to that which occurs at the synaptic cleft during active synaptic activity.
Horizontal cells of the mouse retina contain glutamic acid decarboxylase-like immunoreactivity during early developmental stages
Authors: Schnitzer J , Rusoff AC
Published: March 2018

We have used an antiserum to L-glutamic acid decarboxylase ((GAD), a synthesizing enzyme for gamma-aminobutyric acid (GABA)) to localize putative GABAergic neurons in the developing C57BL/6J mouse retina. At early developmental stages (embryonic day 17 to postnatal day 3), strong GAD-like immunoreactivity is detectable in cell bodies located within the neuroblastic layer. These cells have relatively large cell bodies and extend several sturdy processes which are oriented radially at these early stages. We have identified these cells as horizontal cells. In addition, cell bodies adjacent to the inner plexiform layer and both diffuse and punctate structures within the inner plexiform layer proper have weak GAD-like immunoreactivity at this time. By postnatal day 6, GAD-positive horizontal cell processes begin to form a horizontal network in the newly formed outer plexiform layer. Immunolabeling of amacrine cell bodies and of punctate structures in the inner plexiform layer becomes much stronger at this time, reaching a maximum staining intensity during the second postnatal week. After postnatal day 12, GAD-like immunoreactivity of the horizontal cells begins to decline; in 4-week-old mice the horizontal cells are no longer detectably labeled by this GAD antiserum. At the same time, the GAD-like-immunoreactive material in the inner plexiform layer becomes stratified, forming distinct layers. Amacrine cells and the inner plexiform layer remain GAD positive into adulthood.
A role for bombesin in sensory processing in the spinal cord
Authors: O'Donohue TL , Massari VJ , Pazoles CJ , Chronwall BM , Shults CW , Quirion R , Chase TN , Moody TW
Published: March 2018

Bombesin (BN)-containing neuronal processes were demonstrated in laminae I and II of the dorsal horn of the cat, rat, and mouse spinal cord by immunocytochemistry and radioimmunoassay. Dorsal rhizotomy in the cat resulted in a marked decrease in BN immunoreactivity in the dorsal horn indicating that BN is contained in primary sensory afferents. BN-binding sites were also localized in superficial laminae of the dorsal horn. The presence of both BN and BN-binding sites in the dorsal horn suggested that BN may be involved in sensory processing in the spinal cord. Consistent with this hypothesis, it was demonstrated that an injection of BN into the spinal cord caused a biting and scratching response indicative of sensory stimulation. The effect was similar to that observed after injection of substance P into the cord with the exception that the BN effect lasted about 100 times longer than that induced by substance P. Taken together, these data indicate that BN may be a neurotransmitter of primary sensory afferents to the spinal cord.
Patterns of synaptic input to layer 4 of cat striate cortex
Authors: McGuire BA , Hornung JP , Gilbert CD , Wiesel TN
Published: March 2018

Although cells in layer 4 of cat striate cortex represent the first stage in the cortical processing of visual information, they have considerably more complicated receptive field properties than the afferents to the layer from the lateral geniculate nucleus. In considering how these properties are generated, we have focused on the intrinsic cortical circuitry, and particularly on the projection to layer 4 from layer 6. Layer 6 pyramidal cells were injected with horseradish peroxidase and examined at the light and electron microscopic level. The labeled axon terminals were found to form asymmetric synapses and to show a strong preference for contacting dendritic shafts. Serial reconstruction of dendrites postsynaptic to labeled layer 6 cell axon terminals showed that a large proportion of the postsynaptic dendrites belonged to smooth and sparsely spiny stellate cells, suggesting a selective innervation of these cell types. In contrast, the geniculate projection to layer 4 made synapses primarily with dendritic spines and, as a result, the large majority of terminals ended on spiny cells. Since smooth and sparsely spiny stellate cells are thought to mediate inhibition within the cortex, we suggest that one effect of the layer 6 to layer 4 projection could be to contribute to inhibitory features of the receptive fields of layer 4 cells.
Effects of inferior temporal lesions on discrimination of stimuli differing in orientation
Authors: Holmes EJ , Gross CG
Published: March 2018

Monkeys with inferior temporal (IT) cortex lesions were compared with normal and operated control monkeys on a series of two-choice visual discrimination problems. In some problems, the discriminanda were different patterns or objects whereas, in other problems, the discriminanda were identical patterns or objects presented in different orientations. The animals with IT lesions were significantly impaired in learning to discriminate the different patterns and objects; however, they were not impaired in learning to discriminate stimuli which differed only in orientation by 60 degrees or more. These results help to specify further the role of the IT cortex in visual associative learning by demonstrating that there are some types of visual discriminations which are not sensitive to IT lesions.
Blockade of long-term potentiation in rat hippocampal CA1 region by inhibitors of protein synthesis
Authors: Stanton PK , Sarvey JM
Published: March 2018

Long-term potentiation (LTP) in the hippocampus has attracted attention as a model of neuronal plasticity in the central nervous system. Although accumulating evidence associates protein synthesis with LTP, there is no direct proof that protein synthesis is actually required for the production of LTP. Therefore, we have examined the ability of some inhibitors of protein synthesis to modify LTP in the CA1 region of the rat hippocampal slice. Incubation for 30 min in the presence of emetine, cycloheximide, or puromycin decreased the frequency of occurrence of LTP in field CA1 elicited by repetitive stimulation of the Schaffer collaterals. This blockade was dose dependent and correlated with the ability of individual inhibitors to inhibit incorporation of [3H]valine into proteins. LTP blockade was irreversible for the irreversible inhibitor emetine and was reversible for the reversible inhibitor cycloheximide. Blockade of LTP required a substantial preincubation period to be effective. Even at the highest concentration of emetine used to block LTP, no effect on any intracellularly recorded membrane properties was observed. In contrast, the protein synthesis inhibitor anisomycin was unable to block LTP. Puromycin aminonucleoside, a structural analogue of puromycin which is inactive in inhibiting protein synthesis, was ineffective in blocking LTP. These experiments demonstrate that a variety of protein synthesis inhibitors are able to block the production of LTP in field CA1, suggesting the necessity for a set of newly synthesized or rapidly turned over proteins for hippocampal LTP.
The absence of calcium blocks impulse-evoked release of acetylcholine but not de novo formation of functional neuromuscular synaptic contacts in culture
Authors: Henderson LP , Smith MA , Spitzer NC
Published: March 2018

We have examined the role of calcium-dependent, impulse-evoked release of acetylcholine (ACh) in the formation of functional neuromuscular contacts. Dissociated cell cultures prepared from Xenopus laevis embryos were maintained either in standard medium containing calcium or in calcium-free medium. Both the number of neuron-myocyte contacts and the number of terminations of neurites on myocytes were reduced in Ca- free medium. Intracellular recordings from neuron-myocyte pairs during perfusion with a standard saline revealed that functional synaptic contacts were formed in Ca-free medium, although with a reduced frequency (approximately 30% of controls). Postsynaptic potentials elicited by neuronal action potentials were smaller than those observed after growth in standard medium. The frequency of small, spontaneously occurring potentials was reduced by a factor of 10. Ca-free saline prevented the impulse-evoked release of transmitter from neurons in Ca- free and control cultures. Labeling with alpha-bungarotoxin and iontophoretic application of ACh revealed no ACh receptor clusters in the membrane of myocytes grown in Ca-free medium. Our results suggest that evoked, vesicular release is not required for the initial formation of neuromuscular contacts, although it may be involved in further maturation of synapses. Roles for spontaneous quantal or non- quantal release have not been excluded.
Neurophysin in the hypothalamo-neurohypophysial system. I. Production and characterization of monoclonal antibodies
Authors: Ben-Barak Y , Russell JT , Whitnall MH , Ozato K , Gainer H
Published: March 2018

Seven mouse monoclonal antibodies (IgGs) were produced against rat neurophysins (NPs). Three were specifically directed against vasopressin-associated NP (NP-AVP), and four were specific for oxytocin- associated NP (NP-OT). These specificities were observed in liquid phase assays, immunoblot, and immunoprecipitation experiments. Homozygous Brattleboro rat tissues and extracts, which do not contain vasopressin or NP-AVP, did not react with the anti-NP-AVP antibodies but reacted with high affinity to the anti-NP-OT antibodies. In immunoprecipitation assays the antibodies brought down the appropriate NPs as well as their precursor molecules synthesized in vivo with no detectable cross-reactivity. In solid phase assays where the antigens were presented in a different manner, there was a significant cross- reactivity of the anti-NP-AVP antibodies with NP-OT. The extent of this cross-reactivity in solid phase correlated with the cross-reactivities of the antibodies observed in immunocytochemical studies. These solid phase (and immunocytochemical) data demonstrated that liquid phase specificities and absorption controls of antibodies are inadequate to assess their immunocytochemical (solid phase) specificities. Posterior pituitary extracts from the mouse and frog, as well as purified NPs from the rat, cow, and human were studied for their cross-reactivities to two of the antibodies, PS 36 and PS 45. In liquid phase assays the anti-rat NP-OT antibody, PS 36, reacted only with rat and mouse NPs and did not cross-react with NPs from any of the other species. In contrast, the anti-rat NP-AVP antibody, PS 45, was cross-reactive across species lines including an NP-like antigen extracted from frog posterior pituitaries. Immunoblot staining with these antibodies showed heterogeneity of NP-AVP and NP-OT in the rat posterior pituitary. Analysis of the epitopes for PS 36 and PS 45 indicated the antigenic determinants were located near amino acid positions 80 to 81 in NP-OT and 75 to 86 in NP-AVP, respectively.
Neurophysin in the hypothalamo-neurohypophysial system. II. Immunocytochemical studies of the ontogeny of oxytocinergic and vasopressinergic neurons
Authors: Whitnall MH , Key S , Ben-Barak Y , Ozato K , Gainer H
Published: March 2018

Two anti-neurophysin monoclonal antibodies (MABs), PS 36 and PS 41, described in the preceding paper (Ben-Barak, Y, J.T. Russell, M.H. Whitnall, K. Ozato, and H. Gainer (1985) J. Neurosci. 5:000–000), allowed us to specifically stain for oxytocin-associated neurophysin (NP-OT) or vasopressin-associated neurophysin (NP-AVP) in the hypothalamus of developing rats. Staining with these MABs specific for NP-OT or NP-AVP showed that both types of neurophysin appeared in cells in the developing hypothalamus as early as embryonic day (E16) and continued to increase in immunoreactivity throughout fetal life. The literature indicated that oxytocin appears in the system between E20 and E22, much later than vasopressin (E16 to E17), which we confirmed in immunocytochemical experiments using affinity-purified antisera to these hormones. Since the MABs recognize the specific prohormones as well as the specific mature neurophysins (Ben-Barak, Y., J. T. Russell, M.H. Whitnall, K. Ozato, and H. Gainer (1985) J. Neurosci. 5: 81–97), we conclude that there is a developmental delay between the synthesis of the oxytocin prohormone (pro-oxyphysin) and its processing to form oxytocin and NP-OT. The delay in prohormone processing in the oxytocin cells was correlated with a delay in immunocytochemically detectable neurites as compared to the vasopressin cells. This reduced level of axonal and dendritic immunoreactivity was still obvious in the oxytocin cells at 9 days after birth. In contrast, the clustering of cells to form adult-like hypothalamic nuclei appeared to follow similar time courses for the two types of cells. Adult-like distributions of cells staining for NP-OT and NP-AVP were already apparent in the supraoptic and paraventricular nuclei by E17.
Changes in the electrical properties of olfactory epithelial cells in the tiger salamander after olfactory nerve transection
Authors: Masukawa LM , Hedlund B , Shepherd GM
Published: March 2018

Transection of olfactory nerves causes degeneration of receptor neurons in the olfactory epithelium, followed by generation of new receptor neurons. We have carried out intracellular recordings to document changes in epithelial cell populations during receptor neuron degeneration and regrowth at 1, 2, and 4 weeks following olfactory nerve transection in the salamander. Receptor neurons were greatly reduced in numbers at 1 week, and gradually returned to the normal percentage of intracellular penetrations by 4 weeks. They had a resting membrane potential between -30 and -50 mV and high input resistance, 100 to 600 megohms, characteristically seen in normal epithelium. However, at 1 week, the receptor neurons were able to generate only a single spike in response to injected current, and did not re-acquire their ability to respond repetitively until 4 weeks. Cells with the properties of immature receptor neurons (resting membrane potential between -30 and -50 mV and high input resistance, 100 to 600 megohms, but unable to generate spikes) increased significantly in number in the post-transection period. This correlates with the burst of mitotic activity giving rise to new receptor neurons after nerve transection. Supporting cells changed their properties in the aftermath of transection. One type (A) showed a decrease in resting membrane potential and a small increase in input resistance. A second type (B) showed a very large increase in input resistance. These results imply that the degenerating receptor neurons transmit a signal that leads to changes in the functional properties of the glial-like supporting cells. These may involve changes in the membrane properties or in electrical coupling between cells.
Quantitative in vivo receptor binding. I. Theory and application to the muscarinic cholinergic receptor
Authors: Frey KA , Ehrenkaufer RL , Beaucage S , Agranoff BW
Published: March 2018

A novel approach to in vivo receptor binding experiments is presented which allows direct quantitation of binding site densities. The method is based on an equilibrium model of tracer uptake and is designed to produce a static distribution proportional to receptor density and to minimize possible confounding influences of regional blood flow, blood- brain barrier permeability, and nonspecific binding. This technique was applied to the measurement of regional muscarinic cholinergic receptor densities in rat brain using [3H]scopolamine. Specific in vivo binding of scopolamine demonstrated saturability, a pharmacologic profile, and regional densities which are consistent with interaction of the tracer with the muscarinic receptor. Estimates of receptor density obtained with the in vivo method and in vitro measurements in homogenates were highly correlated. Furthermore, reduction in striatal muscarinic receptors following ibotenic acid lesions resulted in a significant decrease in tracer uptake in vivo, indicating that the correlation between scopolamine distribution and receptor density may be used to demonstrate pathologic conditions. We propose that the general method presented here is directly applicable to investigation of high affinity binding sites for a variety of radioligands.
Efferent synaptic connections of grafted dopaminergic neurons reinnervating the host neostriatum: a tyrosine hydroxylase immunocytochemical study
Authors: Freund TF , Bolam JP , Bjorklund A , Stenevi U , Dunnett SB , Powell JF , Smith AD
Published: March 2018

In adult rats with a unilateral 6-hydroxydopamine-induced destruction of the nigrostriatal dopamine (DA) pathway, grafts of embryonic substantia nigra can establish a new dopaminergic terminal fiber plexus in the previously denervated neostriatum and compensate for some of the behavioral deficits induced by the nigrostriatal lesion. In the present study the synaptic connections of the ingrowing DA fibers from the graft were analyzed ultrastructurally, using immunocytochemical localization of tyrosine hydroxylase (TH), in animals whose lesion- induced motor asymmetry had been completely compensated for by the nigral grafts. In two of the animals, horseradish peroxidase-wheatgerm agglutinin conjugate was injected into the graft in order to trace possible reciprocal afferent connections to the graft from the host striatum. TH-immunoreactive axons from the graft were seen to make abundant symmetric synapses with neuronal elements in the host neostriatum. Between 85 and 90% of these synapses were on dendritic shafts and spines, and the rest were on neuronal perikarya. Two principal targets were identified: dendrites of spiny neurons, the majority of which are likely to be striatal projection neurons; and the cell bodies of giant neurons, most (or perhaps all) of which are known to be cholinergic interneurons. The synapses made on dendritic spines, which constituted about 40% of all TH-positive synapses formed by the TH-positive neurons in the graft, resembled those seen in normal animals, both in that they made contacts with spine necks and in that they invariably were associated with an asymmetric TH-negative synapse contacting the spine head. The innervation of the giant cell perikarya, which constituted about 6% of all TH-positive synapses found, was strikingly abnormal in that the graft-derived TH-positive fibers formed dense pericellular “baskets” selectively around the giant cell bodies. Such arrangements were never seen in the normal striatum, nor did they occur in the intact contralateral striatum in the grafted animals. It is proposed that this apparent dopaminergic hyperinnervation from the graft could provide a powerful inhibition of the cholinergic interneurons in the reinnervated host striatum, and that such an inhibitory mechanism could assist in the graft-induced functional recovery by potentiating the functional effects of DA synapses terminating on the spiny efferent neurons. This dual innervation may thus help to explain why restoration of only a small proportion of the striatal DA innervation by the graft is sufficient to induce complete compensation of, e.g., motor asymmetry in the lesioned rats.(ABSTRACT TRUNCATED AT 400 WORDS)
Characterization of nitrobenzylthioinosine binding to nucleoside transport sites selective for adenosine in rat brain
Authors: Geiger JD , LaBella FS , Nagy JI
Published: March 2018

Nucleoside transport sites in rat brain membrane preparations were labeled with [3H]nitrobenzylthioinosine ([3H] NBI), a potent inhibitor of nucleoside transport systems. The membranes contained a single class of very high affinity binding sites with KD and Bmax values of 0.06 nM and 147 fmol/mg of protein, respectively. The displacement of [3H]NBI binding by various nucleosides, adenosine receptor agonists and antagonists, and known nucleoside transport inhibitors was examined. The Ki values (micromolar concentration) of [3H]NBI displacement by the nucleosides tested were: adenosine, 3.0; inosine, 160; thymidine, 240; uridine, 390; guanosine, 460; and cytidine, 1000. These nucleosides displayed parallel displacement curves indicating their interaction with a common site labeled by [3H]NBI. The nucleobases, hypoxanthine and adenine, exhibited Ki values of 220 and 3640 microM, respectively. Adenosine receptor agonists exhibited moderate affinities for the [3H]NBI site, whereas the adenosine receptor antagonists, caffeine, theophylline, and enprofylline, were ineffective displacers. The Ki values for cyclohexyladenosine, (+)- and (-)-phenylisopropyladenosine, 2-chloroadenosine, and adenosine 5′-ethylcarboxamide were 0.8, 0.9, 2.6, 12, and 54 microM, respectively. These affinities and the rank order of potencies indicate that [3H]NBI does not label any known class of adenosine receptors (i.e., A1, A2, and P). The Ki values of other nucleoside transport inhibitors were: nitrobenzylthioguanosine, 0.05 nM; dipyridamole, 16 nM; papaverine, 3 microM; and 2′-deoxyadenosine, 22 microM. These results indicate that [3H]NBI binds to a nucleoside transporter in brain which specifically recognizes adenosine as its preferred endogenous substrate. This ligand may aid in the identification of CNS neural systems that selectively accumulate adenosine and thereby control “adenosinergic” function.
Opioid pathways in an avian retina. I. The content, biosynthesis, and release of Met5-enkephalin
Authors: Su YY , Watt CB , Lam DM
Published: March 2018

By means of an enzyme-linked immunosorbent assay, the concentration of enkephalin-immunoreactive substances was estimated to be about 25 nM in the chicken retina. The biosynthesis of 3H-Met5-enkephalin in this retina was studied by a pulse-chase incubation technique. Isolated retinas were incubated with 0.2 ml of oxygenated Ringer's solution containing 40 microCi of [3H]methionine and trasylol, a peptidase inhibitor, for 30 min at room temperature. The tissue was then rinsed three times in large volumes of Ringer's solution and incubated in the same solution containing unlabeled methionine (100 micrograms/ml) and trasylol for at least another hour. The products synthesized were extracted in acetic acid and assayed by high performance liquid chromatography (HPLC) and immunoassay. A peak of radioactivity that comigrated with Met5-enkephalin on HPLC and cross-reacted with antibodies against enkephalins was detected. The level of 3H-Met5- enkephalin radioactivity increased approximately 10-fold as the chase- incubation period increased from 0 to 120 min, suggesting that, as in other tissues, Met5-enkephalin may be synthesized as part of a larger precursor. The newly synthesized Met5-enkephalin could be released by depolarization of the retina with high extracellular K+ concentration. Furthermore, this K+-stimulated release was greatly suppressed by 5 mM Co2+ in the medium, suggesting that this release is Ca2+-dependent and may be synaptically mediated.
Cooperative firing activity in simultaneously recorded populations of neurons: detection and measurement
Authors: Gerstein GL , Perkel DH , Dayhoff JE
Published: March 2018

Recent advances in techniques for chronic recording from multiple extracellular microelectrodes allow simultaneous observation of firings of substantial populations of neurons. We describe a new conceptual representation of cooperative behavior within the observed neuronal population. This representation leads to a new technique for detecting and studying functional neuronal assemblies that are characterized by temporally related firing patterns. The representation may be applied to both dynamic and long-term aspects of cooperativity. The basic idea is to map activity of neurons into motions of particles in a multidimensional Euclidean space. Each neuron is represented by a point particle located in this space. In the simplest version of the mapping, each nerve impulse results in an increment in a  associated with that particle; between firings the charges decay. The force exerted by any such particle on any other is, by analogy with some physical forces, proportional to the product of their charges and may depend on the Euclidean distance separating them. The force on a particle directly affects its velocity rather than its acceleration, as with actual particles in a viscous medium. These forces result in aggregation of those particles that correspond to neurons tending to fire together; separate clusters represent independent cooperative groups. Modification of the charges and forces permits inclusion of inhibitory interactions. Identification, measurement, and display of the resulting clusters can be performed with any of a number of algorithms. We illustrate the application of this approach to populations of computer-simulated neurons having both direct and indirect excitatory coupling.
The mapping of visual space onto foveal striate cortex in the macaque monkey
Authors: Dow BM , Vautin RG , Bauer R
Published: March 2018

Visuotopic maps of foveal striate cortex have been obtained by means of single cell recordings from four hemispheres in two awake, behaving macaque monkeys. The numbers of successful separate striate penetration sites in the four hemispheres were 42, 58, 81, and 61, for a total of 242. The resolution of the maps is 10 min of visual angle, nearly an order of magnitude finer than previous maps. No striate receptive field center was found more than 5 min into the ipsilateral visual field. The four maps were sufficiently compatible with one another that they could be combined into one. There are only minor magnification differences between the right and left hemispheres and between the upper and lower quadrants. There is a vertical/horizontal magnification anisotropy of about 1.5:1 in central foveal cortex (0 to 20 min). The composite map can be approximated by the complex logarithmic equation, w = 7.7 * ln (x + iy + 0.33), where w is expressed in millimeters and x and y are expressed in degrees.
Differences in the developmental patterns of three microtubule- associated proteins in the rat cerebellum
Authors: Bernhardt R , Huber G , Matus A
Published: March 2018

The developmental distribution patterns of microtubule-associated proteins (MAPs) 1, 2, and 3 were studied using three monoclonal antibodies. Immunochemical staining at the light and electron microscopic levels demonstrated the specific localization of each MAP in different cellular and subcellular compartments. MAP2, which is specifically associated with dendritic microtubules in the adult brain, is strictly associated with growing dendrites from the onset of their formation. MAP3, a recently described MAP of Mr = 180,000, which in the adult brain is associated with neurofilament-rich axons and glial processes, is associated with axons from the beginning of outgrowth. Although MAP3 is not detectable in granule cells and their parallel fiber axons in the mature cerebellum, it does appear transitorily in these axons during development. During neuronal differentiation, MAP1 is found first in axons and only later in dendrites where the highest concentrations are eventually to be found. These results indicate that the combined appearance of MAP1 and MAP2 (dendrites) or MAP1 and MAP3 (axons) correlates with the appearance of morphologically distinct microtubules and provide further evidence that specific MAPs are molecular determinants of dendritic and axonal formation.
Antibody against nerve growth factor-inducible large external (NILE) glycoprotein labels nerve fiber tracts in the developing rat nervous system
Authors: Stallcup WB , Beasley LL , Levine JM
Published: March 2018

The NILE (nerve growth factor-inducible large external) glycoprotein is a 230,000-dalton molecule found on the surface of PC12 cells. Immunologically cross-reactive glycoproteins in the molecular weight range of 215,000 to 230,000 have been found on many types of neurons in culture. Using immunohistochemical methods, we have shown that NILE- related glycoproteins are present in neuronal fiber tracts of the developing rat brain. Antibody against the NILE glycoprotein specifically labels processes that appear identical to those recognized by antibodies against the neurofilament triplet of proteins. These processes are clearly distinct from the radial glial fibers recognized by antibody against the intermediate filament protein vimentin. NILE glycoprotein is not distributed uniformly over the entire neuronal surface but is concentrated on neurites and is much less abundant on cell bodies. NILE-positive fiber tracts are first seen in the spinal cord and rhombencephalon on embryonic day 11 and over the next 2 days appear in the mesencephalon and diencephalon. Staining in the telencephalon is not seen until embryonic day 15. The appearance of NILE immunoreactivity in these various regions closely parallels the appearance of neurofilament polypeptides, suggesting that NILE-related glycoproteins are present during the early phases of fiber tract formation. This idea is supported by the finding that the NILE glycoprotein can be found postnatally in parts of the nervous-system such as the cerebellar cortex and olfactory bulb which undergo major histogenesis during the postnatal period. In the cerebellum the appearance of NILE immunoreactivity in the two major fiber zones, the molecular layer and the white matter, parallels the development of the fiber structure of these layers. These findings support tissue culture studies which suggest a role for the NILE glycoprotein in mediating nerve fiber fasciculation.
Structure of axon terminals and active zones at synapses on lizard twitch and tonic muscle fibers
Authors: Walrond JP , Reese TS
Published: March 2018

The freeze-fracture technique was used to study differences in membrane structure which could explain differences in the number of quanta released from axon terminals on twitch and tonic muscle fibers in Anolis intercostal muscles. The protoplasmic leaflets of axon terminals facing lizard twitch muscle fibers have intramembrane particle specializations characterized by two parallel linear particle arrays each composed of two particle rows which lie perpendicular to the axis of shallow ridges in the axolemma. During K+ depolarization, vesicles open between the arrays, confirming that these structures are the active zones for synaptic vesicle opening. Active zones at axon terminals on tonic fibers are defined by one linear particle array composed of two parallel particle rows oriented along the axis of a shallow presynaptic ridge; vesicles open beside these arrays. Thus, there are more particles near active zone vesicles in terminals on twitch fibers. Even though terminals on twitch and tonic muscle fibers seem to have similar numbers of synaptic vesicles associated with their active zones, a presynaptic action potential is reported to release at least 10 times more quanta from terminals on twitch fibers. We postulate that the differences in quantal output are related to the observed differences in the number of active zone particles flanking synaptic vesicles at the active zone. Indeed, the correlation between the distribution of these particles and the level of transmitter release provides additional support for the idea that they are the calcium channels which couple transmitter release to the action potential.
The sharpening of frequency tuning curves requires patterned activity during development in the mouse, Mus musculus
Authors: Sanes DH , Constantine-Paton M
Published: March 2018

Neural activity has been implicated as having both a trophic function and a role in synaptic specificity. Sensory deprivation studies in a large number of developing systems have resulted in the pathological morphology of neurons and abnormal response properties. If the relative timing of discharge among afferent terminals is a cue employed by the developing system to refine the array of synaptic connections, then altering the discharge patterns should hinder this process. In the present experiments, we investigate the role played by the temporal pattern of neural activity during the ontogeny of frequency tuning in the mouse central auditory system. Postnatal animals were exposed to acoustic stimuli, repetitive clicks, that continuously entrained a large proportion of primary afferents from the onset of hearing until an age at which tuning curves should have been adult-like. The amount of fatigue to repetitive clicks was characterized at the level of the eighth nerve and inferior colliculus in normal animals. Frequency tuning curves obtained from the inferior colliculus were used as an assay for the specificity of neural connections. Click-reared animals had significantly broader tuning curves than did normally reared mice, particularly for units with best frequencies in the 10- to 15-kHz range. Furthermore, it was found that this change could not be attributed to the selective loss of the sustained component of the response. The affected range is interpreted in terms of the frequency spectrum of the click and the fact that lower frequency regions of the inferior colliculus were found to habituate rapidly. The click-rearing environment did not appear to affect unit spontaneous activity or response latency, nor did it alter the tonotopic map in the inferior colliculus. We argue against the possibility of cochlear damage based on threshold and high frequency cutoff measurements. Mice were reared in a second acoustic environment, repetitive pulses of two added frequencies, as a control for the effects of the click stimulus. This rearing paradigm did not lead to a broadening of tuning curves. It did, however, alter the properties of bimodal tuning curves. For units with bimodal tuning curves having best frequencies in the range of the rearing frequencies, it was found that the second excitatory area had a lower than normal threshold. In addition, the frequency range separating the peaks of the two excitatory regions was statistically smaller. These results are discussed with reference to the specific frequencies used in the rearing paradigm.
The neurotoxicity of excitatory amino acids is produced by passive chloride influx
Authors: Rothman SM
Published: March 2018

In the 15 years since the neurotoxic properties of glutamate and related amino acids were first described, there has been no thoroughly convincing explanation of the pathophysiology of excitatory amino acid- induced neuronal death. These substances depolarize central neurons, increase the frequency of neuronal discharge, and augment synaptic activity, leading to the suggestion that one or more of these properties may in some way be responsible for toxicity. More recently, an excessive calcium influx triggered by amino acids has been implicated in this process. As isolation of the different factors potentially involved in amino acid neurotoxicity is virtually impossible in vivo, dispersed hippocampal cultures were used to define the pathophysiology of this process in vitro. The toxicity of glutamate, N-methyl-D-aspartate, and kainate was unaffected when calcium was deleted and tetrodotoxin added to the balanced salt solution bathing the cultures. In parallel experiments, the calcium ionophore A23187 was not toxic in the presence of calcium. These experiments failed to confirm a role for neuronal activity or calcium influx in this process. However, when depolarization was blocked by deleting sodium from the control salt solution, neither glutamate, N- methyl-D-aspartate, nor kainate produced obvious changes. Alternately, when passive chloride influx was prevented by largely deleting chloride from the bath, the cells were also unchanged by the amino acids. Further experiments showed that depolarization produced by high external potassium concentrations or veratridine was also toxic, but only in the presence of external chloride. These experiments suggest that the pathophysiology of amino acid neurotoxicity may be rather straightforward.