bluuebunny/crossref_metadata_2025 huggingface dataset:
Influence of nerve growth factor on neurofilament gene expression in mature primary sensory neurons
Authors: Verge VM , Tetzlaff W , Bisby MA , Richardson PM
Published: March 2018

To analyze the possible influence of nerve growth factor (NGF) on neurofilament synthesis in primary sensory neurons, adjacent cryostat sections of lumbar dorsal root ganglia (DRG) from adult rats were processed for either NGF-receptor radioautography or in situ hybridization with a neurofilament cDNA probe. Labeling by both procedures was quantified with computer assistance for approximately 300 neurons in each of selected ganglia. For uninjured neurons, no correction was detected between NGF binding and neurofilament mRNA, even after infusion of NGF into the lumbar subarachnoid space for 1 week. One or 3 weeks after sciatic nerve transection, neurofilament labeling densities in large DRG neurons were sharply reduced and the normal bimodal pattern in frequency histograms had become unimodal. Intrathecal infusion of NGF counteracted this injury-induced reduction of neurofilament mRNA but only in neurons with high-affinity NGF receptors. To explain the effects of NGF on axotomized neurons and the normal diversity of neurofilament gene expression among neurons with NGF receptors, we postulate that NGF permits NGF-sensitive DRG neurons to respond differentially to a second factor stimulating neurofilament synthesis.
Bilateral alterations in local cerebral glucose utilization following intranigral application of the GABAergic agonist muscimol
Authors: Dermon CR , Pizarro P , Georgopoulos P , Savaki HE
Published: March 2018

Rates of cerebral glucose utilization were measured by means of the autoradiographic 2-deoxy-D-[1-14C] glucose technique in 70 anatomically discrete central nervous structures in conscious awake rats following unilateral intranigral application of the GABAergic agonist muscimol. Intranigral injection of 1.3 microliters 1 microM muscimol (0.15 ng) induced increases in glucose consumption locally in the substantia nigra reticulata (by 87%), distally in the contralateral reticulata, red nucleus, nucleus accumbens, and prefrontal cortex, and bilaterally in the pyriform cortex, as compared to values in control animals. Intranigral injection of 1.3 microliters 1 mM muscimol (150 ng) effected a local metabolic activation in the substantia nigra reticulata (by 111% compared to the control group) and in compacta (by 18%), as well as a distal activation in the contralateral reticulata (by 39%) and contralateral compacta (by 29%). Beyond the structures affected by the lower dose, the higher dose of muscimol elicited widespread bilateral increases in glucose metabolism in the rat brain. Among the principal nigral reticulata efferent projections, the deep superior colliculi displayed ipsilateral metabolic activation (by 30%), whereas the parafascicular, mediodorsal, and ventromedial thalamic projecting areas, as well as the pedunculopontine nucleus, displayed bilateral activations compared to the control animals. The ventromedial and ventrolateral thalamic nuclei contralateral to the injected substantia nigra reticulata were 20% activated compared to the ipsilateral homologous structures and 30% activated compared to the control rats. The areas that send afferent projections to the reticulata (globus pallidus, entopeduncular and subthalamic nuclei) were mainly activated contralateral to the injected reticulata compared to values for control animals. In general, following intranigral muscimol (1 mM) injection, glucose metabolism was activated to a larger extent on the side contralateral to the injection than on the ipsilateral side. It is suggested that the present findings are due to a presynaptic nigral effect of muscimol on the GABAergic autoreceptors of the striatonigral terminals and to a consequent disinhibition of the reticulata GABAergic output.
Effects of patterned electrical activity on neurite outgrowth from mouse sensory neurons
Authors: Fields RD , Neale EA , Nelson PG
Published: March 2018

A noninvasive method of electric stimulation was used in cell culture preparations to determine the effects of patterned electrical activity on the morphology and motility of mammalian central nervous system growth cones. Neurites from dorsal root ganglion (DRG) neurons of fetal mice were allowed to grow under the barrier of an insert placed in culture dishes. The insert confined the cell bodies within separate experimental and control compartments, and provided a means of exciting action potentials in the growing neurites by extracellular current pulses delivered across the barrier. A phasic pattern of stimulation caused immediate retraction of the filopodia and lamellipodium. Further outgrowth was halted and in many cases retraction of the neurite ensued. No changes in morphology or growth cone motility were evoked by electric stimulation when action potentials were blocked with 1 microM tetrodotoxin (TTX). These effects depended on the rate, pattern, and duration of stimulation. Phasic stimulation was more effective than stimulation with the same number of impulses delivered at a constant frequency. An important new observation was that cultures exposed to phasic stimulation for several hours contained actively growing neurites with normal growth cones which were insensitive to the stimulus. This apparent accommodation in neurites exposed to chronic stimulation may involve processes that regulate calcium conductance or buffering. Cessation of neurite outgrowth by action potentials could represent one mechanism linking morphological and functional characteristics in the developing CNS of mammals, by stabilizing the outgrowth of neurites forming appropriate synaptic contacts and leading to the retraction of growth cones from collaterals that have not formed appropriate contacts at the time the neuron enters into a functionally active circuit.
Ultrastructural localization of tyrosine hydroxylase in the rat ventral tegmental area: relationship between immunolabeling density and neuronal associations
Authors: Bayer VE , Pickel VM
Published: March 2018

Dopaminergic neurons of the A 10 cell group in the rat ventral tegmental area (VTA) exhibit electrical and dye coupling. Also, the activity of these neurons at least partially reflects their content of tyrosine hydroxylase (TH), the rate-limiting enzyme in catecholamine biosynthesis. We examined the ultrastructural localization of TH to determine the morphological features of dopaminergic neurons in the VTA and the relationships between their TH immunoreactivity content and afferent input. Antiserum against the trypsin-treated form of TH was localized using peroxidase-antiperoxidase (PAP) and immunoautoradiographic methods. Immunoreactivity was detected in perikarya, dendrites, and terminals. The perikarya contained the usual organelles, as well as cilia, lamellar bodies, and subsurface cisterns. Qualitative evaluation of peroxidase reaction product and quantitative analysis of the number of silver grains/unit area revealed varying amounts of TH immunoreactivity in nuclei and cytoplasm. Lightly or intensely labeled nuclei were not necessarily associated with corresponding cytoplasmic labeling density. However, cytoplasmic labeling directly corresponded to the relative frequencies of neuronal appositions and synaptic input. Those neurons with less dense cytoplasmic PAP product received fewer synaptic contacts and were less frequently in apposition to other TH-labeled soma and dendrites than neurons displaying relatively more dense cytoplasmic PAP product. Analysis of single sections revealed that 67% (n = 71) of all TH- labeled somata and 15% (n = 2431) of all TH-labeled dendrites were in apposition to other TH-labeled soma or dendrites. TH-labeled terminals were rarely detected and contained relatively low levels of immunoreactivity. The majority of labeled terminals (n = 29/46) formed synapses with labeled soma and dendrites. Unlabeled terminals (n = 2424) in contact with TH-labeled dendrites appeared to form predominantly symmetric synapses. Ten percent (n = 248) of the unlabeled terminals dually synapsed onto adjacent immunoreactive dendrites, perikarya, or dendrite and perikaryon. We conclude that in the rat VTA, (1) detected TH immunoreactivity in cytoplasm, but not nucleus, corresponds to the level of feedback principally from nondopaminergic afferents; (2) dendrodendritic as well as axodendritic synapses between TH-immunoreactive neurons may mediate dopaminergic autoinhibition; and (3) gap junction-like appositions between neurons and convergent inputs from unlabeled terminals onto TH-immunoreactive profiles provide an anatomical substrate whereby cellular activities might be coordinated under certain conditions.
Effects of aging on nicotinic and muscarinic autoreceptor function in the rat brain: relationship to presynaptic cholinergic markers and binding sites
Authors: Araujo DM , Lapchak PA , Meaney MJ , Collier B , Quirion R
Published: March 2018

The main objective of the present work was to determine whether the regulation of ACh release by nicotinic and muscarinic autoreceptors is compromised in the aged rat brain. For this, the effects of the nicotinic agonist N-methylcarbamylcholine (MCC) and the muscarinic-M2 antagonist AF-DX 116 on ACh release from brain slices of young (3-month- old), adult (9-month-old), and aged (27-month-old) rats were tested. The ability of MCC to enhance spontaneous ACh release in hippocampal, cerebral cortical, and cerebellar slices was only modestly altered with age. In contrast, the sensitivity of muscarinic autoreceptors in the aged hippocampus and cerebral cortex, but not the striatum, to blockade by the muscarinic-M2 antagonist AF-DX 116 was severely attenuated. To assess whether the age-related changes in cholinergic autoreceptor function may be due to deficits in presynaptic cholinergic markers, we tested whether choline acetyltransferase (ChAT) activity, basal and evoked ACh release, and nicotinic and muscarinic binding sites are altered in the aged rats. ChAT activity in forebrain regions was decreased in the aged compared to the young and mature adult rats. Furthermore, the potassium-evoked, but not the spontaneous, release of ACh was markedly depressed in striatal, hippocampal, and cortical slices of aged rats. The densities of nicotinic and muscarinic-M2 binding sites, assessed using 3H-MCC and 3H-AF-DX 116 as selective ligands, respectively, were markedly reduced in homogenates of the striatum, hippocampus, cerebral cortex, and thalamus of aged rats. In contrast, muscarinic-M1 sites, selectively labeled with 3H-pirenzepine, were not affected. Therefore, it appears that age-related decrements in ChAT activity and in muscarinic-M2, but not nicotinic, binding sites in the rat brain are reflected in a decreased function of muscarinic-M2 autoreceptors. However, the positive correlation between loss of ChAT activity, decreased muscarinic-M2 binding sites, and impaired muscarinic autoreceptor function is clearly tissue dependent.
The role of directionally selective neurons in the perception of global motion
Authors: Pasternak T , Albano JE , Harvitt DM
Published: March 2018

Dynamic random dot targets consisting of many localized motion vectors have been used to study the pooling of local motion signals into a global motion percept (Williams and Sekuler, 1984). In such displays, the dots are displaced with a constant step size and the direction of motion for each dot is chosen at random from a specified distribution. When the distribution extends over 360 deg, the display consists only of local random motion of individual dots and no coherent motion is reported. However, when the distribution is less than 360 deg (biased), the stimulus appears to flow in a single direction. We examined the effects of reducing the number of directionally selective (DS) cortical neurons on this integration process. Normal cats and cats with severely reduced proportions of DS neurons were trained on 2 direction discrimination tasks. The discrimination of opposite directions was examined while varying either the range of directions of local motion, or the proportion of dots moving with biased distribution. When all dots in the display were directionally biased, cats with reduced numbers of DS neurons performed the task as well as normal cats and humans (threshold range: 280-320 deg). However, when the proportion of biased dots decreased, these animals had severe deficits. Thus, in the absence of noise, even a very small number of DS neurons can perform spatial pooling of local directional signals, and support normal discrimination of opposite directions. However, a full complement of directional detectors appears necessary when the motion signal is masked by noise. The discrimination of small differences in direction revealed far more severe deficits, even when all the dots in the display were directionally biased (no noise).(ABSTRACT TRUNCATED AT 250 WORDS)
Nerve growth factor infusion into the denervated adult rat hippocampal formation promotes its cholinergic reinnervation
Authors: Hagg T , Vahlsing HL , Manthorpe M , Varon S
Published: March 2018

The well-documented but little-understood failure of lengthy axonal regeneration after injury of the adult mammalian CNS may be caused by an insufficient availability of local growth-promoting factors. If so, identifying and supplying the missing factors may result in better central axonal regeneration. This hypothesis was tested in an adult rat CNS model in which peripheral nerve grafts were placed into a lesion cavity between the septum and hippocampal formation. Continuous infusion of nerve growth factor (NGF) into the dorsal hippocampal tissue dramatically enhanced and accelerated the regrowth and penetration of cholinergic axons into the hippocampal formation. Thus, NGF can overcome the apparent resistance of the hippocampal CNS tissue to cholinergic reinnervation.
Cyclic AMP-induced slow inward current: its synaptic manifestation in Aplysia neurons
Authors: Kehoe J
Published: March 2018

Three presynaptic neurons, monosynaptically connected to the medial cells of the pleural ganglion of Aplysia californica and previously shown to elicit cAMP-mediated diminutions in K conductance in those cells (Kehoe, 1985a, b), were shown to elicit still another slow synaptic current that resembles the cAMP-induced cationic current described in the preceding paper (Kehoe, 1990). The synaptic current elicited by these so-called “blocking” neurons was compared, in hyperpolarized medial cells, with the current induced by an intracellular injection of cAMP. It was found that (1) both currents show an outward rectification, (2) both currents are enhanced and prolonged by phosphodiesterase inhibitors (as well as by intracellular acidification of the postsynaptic neuron and by bath-applied caffeine), and (3) both currents react in the same way to changes in (Ca)0, showing a net enhancement when (Ca)0 is reduced and, conversely, a marked diminution when extracellular (Ca)0 is increased. The increase in amplitude of the slow synaptic current in low-Ca solutions and its decrease in high-Ca seawater are contrary to the changes that would be expected from the known effects of Ca on transmitter release at chemical synapses, revealing the overriding importance of the postsynaptic block by Ca. The data presented here strongly suggest that both the slow inward current and the diminutions in K conductance induced by the firing of the 3 blocking neurons are mediated by cAMP. Like the 2 cAMP-mediated diminutions in K conductance (Kehoe, 1985a, b), the cAMP-activated slow inward current, because of its atypical voltage dependence, both depolarizes the medial cell and causes an increase in its input resistance at resting potential. Consequently, the synaptically activated increase in cAMP prolongs the excitability of the medial cells for up to tens of seconds after the end of presynaptic firing.
Cyclic AMP-dependent phosphorylation of a neuronal acetylcholine receptor alpha-type subunit
Authors: Vijayaraghavan S , Schmid HA , Halvorsen SW , Berg DK
Published: March 2018

Chick ciliary ganglion neurons have nicotinic acetylcholine receptors (AChRs) that mediate synaptic transmission through the ganglion. A cAMP- dependent process has previously been shown to enhance the ACh response of the neurons 2- to 3-fold without requiring the synthesis of new receptors. We show here that the receptors can be phosphorylated in situ by a cAMP-dependent process. The phosphorylation occurs predominantly on components of 50 and 58 kDa. Both derive from putative ligand-binding alpha 3 subunits, with the smaller phosphorylated species probably representing a degradation product of the larger. The increase in receptor phosphorylation caused by incubating the neurons with a cAMP analog parallels the increase observed in the ACh response, with respect to both time course and relative extent. The phosphorylation of ciliary ganglion AChRs differs from that reported for electric organ AChRs, which occurs primarily on the non-ligand- binding gamma and delta subunits and increases the rate of agonist- induced receptor desensitization.
Ion channels in axon and Schwann cell membranes at paranodes of mammalian myelinated fibers studied with patch clamp
Authors: Wilson GF , Chiu SY
Published: March 2018

While recent studies have established the presence of voltage-gated ion channels on Schwann cells in culture and on freshly isolated fibers from mature mammals, an important issue not yet explored is whether Schwann cell channels are regionally specialized. In the nodal region, the intimate association between the Schwann cell and its axon suggests that this is a likely site for functional specialization. Here, we examine whether there is a localized expression of channels in the Schwann cell paranodal regions, in a manner similar to that already shown for the nodal axon. Cell-attached and outside-out patch-clamp recordings were made from paranodal regions of rat myelinated sciatic nerve fibers where the myelin on both sides of the node was retracted by enzymatic treatment. Even though no myelin was visible on the surface of the retracted paranode, significant portions of this surface were found to stain positively with a marker (anti-galactocerebroside) for Schwann cell membranes, suggesting that part of the axon still was covered by glial membranes. Using Lucifer yellow in the recording pipettes, we observed that the dye diffused into either axons or Schwann cells when the membrane under the tip was ruptured. Using this as a criterion to identify membranes obtained from retracted paranodes, we found delayed and inwardly rectifying potassium channels on both axon- and Schwann-derived patches. However, sodium channels were detected only in axon patches. This is the first report that voltage- gated glial channels are present in immediate vicinity to axons of the PNS. This finding, coupled with earlier reports that functional channels are absent in soma of mature myelinating Schwann cells, suggests that ion channels in these cells are regionally specialized for functional interaction with axons.
Excitation of locus coeruleus neurons by vasoactive intestinal peptide: role of a cAMP and protein kinase A
Authors: Wang YY , Aghajanian GK
Published: March 2018

In accord with previous studies, it was found that vasoactive intestinal peptide (VIP), a powerful activator of adenylate cyclase, and cAMP-active agents (i.e., 8-Br-cAMP, forskolin, and Ro20-1724) increased the firing rate of noradrenergic neurons in the locus coeruleus (LC) by inducing an inward current. The response to VIP was usually more rapid and larger in a subpopulation of LC neurons with subthreshold rhythmic oscillations in membrane potential (oscillatory cells) as compared to nonoscillatory cells. In either case, the inward currents elicited by VIP and cAMP-active agents were found to be nonadditive, suggesting the action of VIP, at least in part, is via the same mechanism as that of cAMP-active agents. Intracellular application of a specific protein (or related peptide) inhibitor of cAMP-dependent protein kinase markedly attenuated the activation induced by either cAMP-active agents or VIP, suggesting that cAMP-dependent protein kinase (protein kinase A), presumably through protein phosphorylation, plays a role in the action of VIP. Taken together, the results provide evidence that cAMP and protein kinase A are involved in mediating the electrophysiological actions of VIP on LC neurons.
The cold stability of microtubules increases during axonal maturation
Authors: Watson DF , Hoffman PN , Griffin JW
Published: March 2018

The development of cold-stable microtubules (MTs) was studied in maturing rat sciatic nerves. From 4 to 10 weeks of age, there was a large increase in the proportion of tubulin associated with stable MTs. A greater fraction of axonal tubulin than nonaxonal tubulin was associated with stable MTs. The labeled tubulin remaining behind the peak of slow axonal transport was more highly associated with stable MTs than tubulin in the peak itself. Immunoassay confirmed that the sciatic nerve contains a pool of stable MTs not identical to the peak of tubulin transport. The developmental increase in MT stability is not associated with any increase in the acetylation of tubulin or with alterations in the major MT-associated proteins. One aspect of maturation of the axonal cytoskeleton may involve deposition of tubulin into stable MTs that are either stationary or moving slowly with regard to the peak of transported tubulin.
Early unilateral deprivation modifies olfactory bulb function
Authors: Guthrie KM , Wilson DA , Leon M
Published: March 2018

Unilateral olfactory deprivation during postnatal development produces significant structural and neurochemical modifications of the olfactory bulb. In the present report, we describe the functional consequences of such deprivation. Rat pups had a single naris occluded on postnatal day 2 (PN2) to deprive them of early olfactory stimulation. On PN20-22, the occluded naris was reopened, the previously open naris was sealed, and responses of the deprived olfactory bulb to odors were assessed using both single-unit recording from mitral/tufted cells and quantitative 14C-2-deoxyglucose (2-DG) autoradiography. While the response properties of individual odor-stimulated mitral/tufted cells were not altered by early deprivation, spontaneous activity was depressed, and there was a significantly higher incidence of odor-responsive mitral/tufted cells in deprived compared to nondeprived bulbs. In addition, odor-stimulated deprived bulbs demonstrated greater uptake of 2-DG than did non-deprived bulbs. Together, these data indicate that the olfactory system demonstrates an increased responsiveness to sensory cues following early deprivation.
The recovery of forelimb-placing behavior in rats with neonatal unilateral cortical damage involves the remaining hemisphere
Authors: Barth TM , Stanfield BB
Published: March 2018

Following unilateral lesions of the somatic sensorimotor cortex (SMC) in neonatal, but not adult, rats, an aberrant ipsilateral corticospinal projection originates from the undamaged hemisphere (Hicks and D'Amato, 1970; Leong and Lund, 1973; Castro, 1975). We have evaluated the contribution of the hemisphere contralateral to a unilateral lesion of the SMC in the recovery of tactile forelimb-placing behavior. Neither adult-lesioned or neonatally lesioned animals show evidence for placing deficits with either forelimb when tested 30 or 42 d after the lesion. However, in adult-lesioned animals, a subsequent lesion of the undamaged SMC on postlesion day 42 produces placing deficits only with the forelimb contralateral to the second lesion, while such a second lesion in the neonatally lesioned rats results in placing deficits with both forelimbs. Anatomical observations in the animals used for behavioral analyses confirm previous reports of a substantial ipsilateral corticospinal projection in rats with unilateral SMC damage as neonates and demonstrate that many of these aberrant fibers recross the midline within the spinal cord to arborize extensively within the ipsilateral spinal gray. These findings indicate that, following unilateral SMC lesions in neonates, the contralateral hemisphere mediates some aspects of the recovery of forelimb placing. The aberrant ipsilateral corticospinal projection may provide the anatomical substrate through which the cortex effects this recovery.
Developmental expression of the 43K and 58K postsynaptic membrane proteins and nicotinic acetylcholine receptors in Torpedo electrocytes
Authors: LaRochelle WJ , Witzemann V , Fiedler W , Froehner SC
Published: March 2018

The expression of the postsynaptic 43-kDa and 58-kDa proteins and actin during development of the Torpedo marmorata electric organ was compared to that of nicotinic acetylcholine receptors (AChRs). Western blot analysis demonstrates that AChRs and proteins of 43 kDa (43K protein) and 58 kDa (58K protein) are all present prior to synaptogenesis. Subsequently, levels of all 3 synaptic proteins increase dramatically during differentiation and innervation of electrocytes. In contrast, actin is present in relatively high concentrations at early times and decreases thereafter. The equimolar ratio of AChRs and the 43K protein found in the adult electric organ is established early in development. Furthermore, the AChR and 43K protein share a common postsynaptic localization in electrocytes following synapse formation. Aggregates of the AChR that form at the ventral pole of the oval-shaped electrocytes prior to innervation, however, show no detectable immunofluorescence staining with anti-43K monoclonal antibodies. Therefore, in some cases, aggregation of AChRs occurs without the 43K protein.
Survival effect of ciliary neurotrophic factor (CNTF) on chick embryonic motoneurons in culture: comparison with other neurotrophic factors and cytokines
Authors: Arakawa Y , Sendtner M , Thoenen H
Published: March 2018

In previous studies, it has been demonstrated that ciliary neurotrophic factor (CNTF) has a potent survival effect on various populations of neurons in culture, in particular, neurons isolated from chick ciliary, dorsal root sensory, and sympathetic ganglia (Barbin et al., 1984). After recent investigations demonstrated that CNTF prevents the degeneration of motoneurons in newborn rats after axonal lesion (Sendtner et al., 1990), the question arose as to whether CNTF also has a survival effect on embryonic chick motoneurons at the developmental stage where physiological cell death occurs. To study this, it was essential to develop an isolation and culture procedure for the survival of chick E6 spinal motoneurons in which non-neuronal cells were eliminated and the motoneurons were highly enriched. In these cultures, virtually all of the initially plated motoneurons survived for at least 3 d in the presence of muscle extract, which was chosen as a positive control. Retrograde labeling of the motoneurons prior to their isolation showed that there is more than an 80% enrichment for motoneurons by the method used. The retrogradely labeled neurons also fulfilled the morphological criteria (diameter of neurons, appearance of processes) to identify motoneurons independent of retrograde labeling. Under these conditions, CNTF at a concentration of 1.5 ng/ml (EC50, 0.023 ng/ml) supported maximally 64% of the initially plated spinal motoneurons after 3 d and 53% after 6 d (the longest time period investigated). Other neurotrophic factors, such as NGF, brain-derived neurotrophic factor (BDNF), and neurotrophin-3, had no survival effect at all, even at concentrations up to 10 micrograms/ml for NGF and BDNF.(ABSTRACT TRUNCATED AT 250 WORDS)
Motor nerve regulates muscle extracellular matrix proteoglycan expression
Authors: Fadic R , Brandan E , Inestrosa NC
Published: March 2018

Denervation of rat leg muscles caused a 2-3-fold increase in 35S- sulfate and 3H-glucosamine incorporation into proteoglycans of the muscle extracellular matrix. The size of the proteoglycans and the glycosaminoglycan chain length and degree of sulfation were unchanged. Because the rate of degradation of proteoglycans was also unchanged by denervation, we infer that denervation increases proteoglycan synthesis. Muscle reinnervation restored the original rate of synthesis of proteoglycans. Paralysis of innervated muscle caused increased incorporation of sulfate comparable to that seen in denervation. Thus motor nerve activity appears to regulate the level of proteoglycans in the muscle extracellular matrix.
Changes in instrumentally and classically conditioned limb-flexion responses following inferior olivary lesions and olivocerebellar tractotomy in the cat
Authors: Voneida TJ , Christie D , Bogdanski R , Chopko B
Published: March 2018

Lesions were placed in various parts of the inferior olivary nucleus and olivocerebellar tract in an attempt to define further the role of the inferior olive in the performance of a conditioned limb-flexion response (LFR) in cats. Thirty-two cats were trained to make an LFR using either classical or instrumental conditioning. The conditioned stimulus (CS) was a tone, and the unconditioned stimulus (US), a shock to the forelimb. Following training, lesions were placed in various parts of the inferior olivary nucleus in 20 animals (radio frequency lesions, 17; electrolytic lesions, 3). Midline section of the olivocerebellar tract was carried out in 12 animals. The degree of conditioned-response (CR) loss resulting from a given lesion was closely related to the precise locus of the lesion. Rostromedial olivary lesions, which included the spino- and cortico-olivary forelimb projection zones and the olivocerebellar projection area, resulted in varying degrees of CR loss (from partial to near total), deregulation of response latency, and a significant reduction of response amplitude. The CR deficit and degree of post-operative CR recovery were directly related to the extent of damage to this part of the rostromedial olive. Lesions restricted to the caudal olive or to caudal levels of the olivo- cerebellar tract resulted in no postoperative CR deficits. Animals with caudal lesions, however, showed more severe general motor deficits postoperatively than did those with rostromedial lesions and loss of the CR. Prolonged training of animals with the most complete CR deficits resulted in some relearning, but response patterns were typified by long-latency, low-amplitude CRs and a highly unstable response pattern.
Nerve growth factor infusion in the primate brain reduces lesion- induced cholinergic neuronal degeneration
Authors: Tuszynski MH , U HS , Amaral DG , Gage FH
Published: March 2018

NGF is a protein that promotes survival, differentiation, and process extension of selected neuronal populations during development and, in some cases, in the mature organism. Previous lesion and aging studies in the rat have shown that intracerebroventricular NGF infusions can prevent degenerative changes in basal forebrain cholinergic neurons. We sought to determine whether salutory effects of NGF occur in the primate brain. Cholinergic fibers of the septohippocampal projection in the primate were surgically transected, followed by infusion of either a vehicle or an NGF solution into the ventricular system for a 4-week period. Quantification of cholinergic neurons in the medial septal nucleus at the end of the infusion period demonstrated that only 45 +/- 5% of cholinergic neurons could be identified after fornix lesions in vehicle-infused animals, whereas 80 +/- 6% of neurons were visible in NGF-treated animals. Thus, NGF substantially reduced lesion-induced cholinergic neuronal degeneration in the adult primate brain. This finding may be relevant to the hypothesis that NGF has potential use as a cholinergic “neurotrophic-factor therapy,” given that loss of basal forebrain cholinergic neurons is common in Alzheimer's disease.
Development of the retinotectal projection in zebrafish embryos under TTX-induced neural-impulse blockade
Authors: Stuermer CA , Rohrer B , Munz H
Published: March 2018

The influence of neural activity on the morphology of retinal-axon- terminal arbors and the precision of the developing retinotectal projection in zebrafish embryos was explored. Terminal-arbor morphology and their distribution in the tectum was determined with anatomical fiber-tracing methods using the fluorescent dyes dil and diO. To allow development under activity-deprived conditions, TTX was injected into the eyes of 30-38-hr-old zebrafish embryos at concentrations that effectively blocked neural activity both in retinal ganglion cells and throughout the CNS. Much like axons with normal neural-activity patterns, activity-deprived axons from dorsal and ventral and from temporal and nasal regions in the retina terminated over retinotopically appropriate and nonoverlapping regions of the tectum. Even after ablation of 1 hemiretina at the time of axonal outgrowth, activity-deprived axons from the remaining hemiretina grew directed toward and arborized selectively within their retinotopically appropriate tectal half in the same way as would nondeprived axons. Besides being retinotopic, the area over which small populations of activity-deprived axons from neighboring ganglion cells arborize is as small as that of active axons. The size of terminal arbors of retinal ganglion cell axons was unaffected by blockade of neural activity. The mean terminal-arbor size was 27 x 18 microns for the TTX-injected and 31 x 22 microns for the control embryos. The tectal coverage of TTX- blocked and control axons was equally small, with values of 1.4% and 1.6%, respectively. These data show that a precisely organized retinotopic map in developing zebrafish forms independent of neural- impulse activity.
Specific binding of substance P aminoterminal heptapeptide [SP(1-7)] to mouse brain and spinal cord membranes
Authors: Igwe OJ , Kim DC , Seybold VS , Larson AA
Published: March 2018

Aminoterminal fragments of substance P (SP) have been previously shown to produce effects distinct, and often opposite, from those produced by the C-terminal of SP. The present investigation was initiated to determine whether N-terminal fragments interact at binding sites distinct from the neurokinin-1 (NK-1) receptor where the C-terminal sequence of SP binds with high affinity, and distinct from mu-opiate receptors, where we have previously shown the N-terminal sequence of SP to interact. A tritium-labeled aminoterminal heptapeptide of SP, 3H- SP(1-7), was synthesized, purified, and used to characterize the binding of a variety of fragments of SP and opioids in the mouse brain and spinal cord membranes. Using the reduction of SP-induced caudally directed biting and scratching behaviors as an index of biological activity, 3H-SP(1-7) was shown to be equipotent to unlabeled SP(1-7). 3H-SP(1-7) was found to bind reversibly to a saturable population of sites. Scatchard analyses of concentration-dependent saturation of binding in the brain indicated a single population of noninteracting sites with a high affinity (Kd = 2.5 nM) and a low capacity (Bmax = 29.2 fmol/mg protein). Kinetic analyses indicated an apparent dissociation equilibrium constant of 2.1 nM. Two populations of binding sites were observed in the spinal cord, one with a very high affinity (Kd = 0.03 nM) and low capacity (Bmax = 0.87 fmol/mg protein), and the other with lower affinity (Kd = 5.4 nM) and intermediate capacity (Bmax = 19.6 fmol/mg protein). Specific agonists for NK-1, NK-2, and NK-3 and delta opioid receptors, carboxyterminal fragments of SP, and a variety of other peptides did not compete at the 3H-SP(1-7) binding sites, but structurally related N-terminal peptides and (D-Ala2, NMe-Phe4, Gly-ol)- enkephalin (DAMGO) were active in displacing the ligand. The binding site for 3H-SP(1-7) appeared to be a membrane-bound complex whose specific binding was dependent on the integrity of both proteins and phospholipids. These studies are the first to characterize the binding sites for the SP N-terminal partial sequence of SP that can be generated by metabolism in vivo. The expanding body of evidence for distinct biological activities of N-terminal metabolites of SP, together with the current characterization of N-terminal binding, strongly support the existence of an N-terminal-directed SP receptor. The characteristics of SP(1-7) binding sites are consistent with those expected for an SP N-terminal receptor.
Discrimination learning alters the distribution of protein kinase C in the hippocampus of rats
Authors: Olds JL , Golski S , McPhie DL , Olton D , Mishkin M , Alkon DL
Published: March 2018

Protein kinase C (PKC), an enzyme that plays an essential role in eukaryotic cell regulation (Nishizuka, 1988; Huang et al., 1989), is critical to memory storage processes both in the marine snail Hermissenda crassicornis and in the rabbit (Alkon et al., 1988; Bank et al., 1988; Olds et al., 1989). Specifically, activation of PKC mimics neurobiological correlates of classical conditioning in both Hermissenda and the rabbit, and the distribution of the enzyme within the rabbit hippocampus changes after Pavlovian conditioning. Here, we report that the amount of PKC, as assayed by specific binding of 3H- phorbol-12,13-dibutyrate (3H-PDBU), decreased significantly within the hippocampal CA3 cell region in rats trained to solve a water maze task either by cognitive mapping or by visual discrimination strategies, but not in control rats. Furthermore, hippocampal lesions interfered with acquisition of both of these tasks. We interpret these findings to support the conclusion that distributional changes of PKC within the mammalian hippocampus play a crucial role in memory storage processes.
The visuotopic component of the multisensory map in the deep laminae of the cat superior colliculus
Authors: Meredith MA , Stein BE
Published: March 2018

A well-defined map of visual space is located in the deep laminae of the cat superior colliculus. The horizontal meridian is oriented rostral-caudal, while the vertical meridian is oriented perpendicular to it in the rostral third of the structure. This map represents the entire contralateral visual field and extends approximately 40 degrees into ipsilateral visual space. Although the deep-laminae visuotopy is similar to that found in the superficial laminae of the same structure, the topographic register among these maps is most secure rostrally but becomes increasingly poorer at more caudal and lateral locations. The combination of 2 features distinguish the deep-layer visual representation from that found in the superficial laminae and in geniculocortical systems: (1) the constituent visual receptive fields are very large (mean diameter, 66.9 degrees), and (2) the majority (greater than 70%) of the neurons composing it receive nonvisual inputs. Because the visual receptive fields of visual-multisensory neurons are significantly larger than those of neighboring neurons that respond only to visual stimuli, far more visual-multisensory neurons are activated by any given visual stimulus. These data, when coupled with those from previous studies, suggest that, from a functional perspective, deep-laminae visual neurons form one component of an integrated multisensory map, and that their topographic organization is essential for the normal dynamics of multisensory integration.
Mouse nerve growth factor prevents degeneration of axotomized basal forebrain cholinergic neurons in the monkey
Authors: Koliatsos VE , Nauta HJ , Clatterbuck RE , Holtzman DM , Mobley WC , Price DL
Published: March 2018

NGF, a trophic polypeptide, is necessary for the normal development and survival of certain populations of neurons in the CNS and PNS. In the CNS, cholinergic neurons of the basal forebrain magnocellular complex (BFMC) are prominent targets of NGF. During rat development, NGF increases the activity of ChAT in these neurons. In adult rats with experimental injury of axons in the fimbria-fornix, NGF prevents degenerative changes in axotomized cholinergic BFMC neurons in the medial septal nucleus (MSN). Because the amino acid sequences of NGF and its receptor (NGF-R) are highly conserved across species, we hypothesized that mouse NGF would also prevent degeneration of cholinergic BFMC neurons in nonhuman primates. Therefore, the present study was designed to test whether fimbria-fornix lesions result in retrograde degenerative changes in basal forebrain cholinergic neurons in macaques, whether these changes are prevented by mouse NGF, and whether the protective effect of NGF is selective for cholinergic neurons of the basal forebrain. Following unilateral complete transection of the fornix, animals were allowed to survive for 2 weeks, during which time half of the subjects received intraventricular NGF in vehicle and the other half received vehicle alone. In animals receiving vehicle alone, there was a 55% reduction in the number of ChAT- immunoreactive cell bodies within the MSN ipsilateral to the lesion; loss of immunoreactive somata was more severe in caudal planes of the MSN. Remaining immunoreactive neurons appeared smaller than those in control, unoperated animals. In Nissl stains, there was no apparent loss of basophilic profiles in the MSN, but cells showed reduced size and intensity of basophilia. Treatment with NGF almost completely prevented reductions in the number and size of cholinergic neurons and had a significant general effect in preventing atrophy in basophilic magnocellular neurons of the MSN, though some basophilic neurons in the MSN did not appear to respond to NGF. Adjacent 7-microns-thick sections stained with ChAT and NGF-R immunocytochemistry revealed that these markers are strictly colocalized in individual neurons in the MSN in controls and in both groups of experimental animals. Thus, mouse NGF profoundly influences the process of axotomy-induced retrograde degeneration in cholinergic BFMC neurons in primates. The in vivo effectiveness of mouse NGF on primate BFMC neurons suggests that mouse or human recombinant NGF may be useful in ameliorating the ACh- dependent, age-associated memory impairments that occur in nonhuman primates.(ABSTRACT TRUNCATED AT 400 WORDS)
Competitive interactions between neurons making axosomatic contacts in the leech
Authors: Gu XN , Muller KJ
Published: March 2018

Axons of lateral nociceptive (N) neurons in leech segmental ganglia wrap certain somata in adjacent ganglia but no somata in their own ganglion. In adults, the N neurons, which accurately regenerate axosomatic wrappings, can be induced to sprout in their own ganglion and wrap target homologues if the ganglion is isolated by cutting the nerve cord. Manipulations that denervate the new targets without injuring the lateral N cell, including focal lesions and protease injections into other N cells, also cause sprouting within 2-4 months. In contrast, cutting the lateral N cell's axons causes little or no sprouting within the ganglion without denervation. Therefore, denervation rather than injury accounts for sprouting within the ganglion. It is concluded that lateral N cells can wrap somata in their own ganglion that are homologues of their usual targets, but they are prevented from doing so by axonal wrappings from N cells in adjacent ganglia.
Immunocytochemical localization of the erythroid glucose transporter: abundance in tissues with barrier functions
Authors: Harik SI , Kalaria RN , Andersson L , Lundahl P , Perry G
Published: March 2018

We investigated the cellular localization and tissue distribution of the glucose transporter protein in the nervous system of the monkey and rat, and in other tissues of the rat, by immunocytochemical methods with monoclonal and polyclonal antibodies to the glucose transporter of human erythrocytes. We found intense immunostaining, indicating a high density of the glucose transporter, in all intraparenchymal blood vessels of the brain and spinal cord, in pial vessels, and in endoneurial capillaries of peripheral nerves, nerve roots, and dorsal root ganglia. Larger blood vessels at the base of the brain and in major fissures did not stain. The only intraparenchymal brain microvessels that did not immunostain were in circumventricular organs. There was no specific immunostaining of neurons or glia, except for tanycytes in the floor of the third ventricle, which immunostained intensely. Vessels of the choroid plexus did not stain, but the choroid epithelium, especially its basal membranes, stained. The only non- neural organ where immunostaining was evident in its microvessels was the testis. In addition to the endothelium of neural and testicular tissues, there was immunostaining in certain epithelial tissues, such as the perineurium of peripheral nerves and nerve roots, the epithelium of the ascending loop of Henle in the kidney, and the epidermis of the skin. Based on these findings, we hypothesize that a high density of the erythroid-type glucose transporter is inherent to many endothelial and epithelial cells that are joined by occluding junctions. However, other epithelial tissues with known occluding intercellular junctions that lack the erythroid-type of glucose transporter may have other types of glucose transporter proteins.
Appetitive feeding behavior of Aplysia: behavioral and neural analysis of directed head turning
Authors: Teyke T , Weiss KR , Kupfermann I
Published: March 2018

The appetitive phase of feeding behavior in Aplysia consists of a behavioral sequence in which the quiescent animal starts to locomote and then assumes a characteristic feeding posture. In this position, head-turning responses can be elicited by a localized food stimulus (seaweed) delivered to the lips or tentacles. In response to brief (open loop) stimulation with seaweed, the animal turns toward the stimulus but greatly overshoots the target. However, the angular velocity and the final turning angle are a function of the eccentricity of the stimulus, progressively increasing with greater eccentricities. In a food-aroused animal, a brief tactile stimulus evokes turning and biting responses similar to those triggered by seaweed, which provides both tactile and chemical stimulation. Upon repeated tactile stimulation, however, the response magnitude decrements rapidly, whereas the magnitude remains high when turning responses are repeatedly elicited by food stimuli. A purely chemical stimulus sometimes can elicit a turning response, but chemical stimuli alone are much less efficacious than tactile stimuli alone. When the stimulus is maintained in a stationary position (closed loop), the animal turns until its mouth is oriented over the food. A turning response to a lateral stimulus can be reduced by an immediately following medial stimulus. To explain the above findings, we propose a form of response substitution, in which the response to the first, lateral stimulus is substituted by a weaker response to a more medial stimulus. No turning response is evoked when the animal is stimulated while performing spontaneous or evoked bites, though biting per se does not interrupt ongoing turning movements. In animals with lesions of the cerebral- buccal connectives, a food stimulus on the mouth is also followed by a reduction of the capacity of stimuli to elicit turning responses. In these lesioned animals, the food stimulus appears to elicit a bite command, though the biting behavior itself does not occur. Thus, it appears that the bite-related gating of stimuli is of cerebral origin, rather than due to the generation of the buccal motor program. The force necessary to power the turning movements was calculated from the trajectories of the movements. The results indicate that a power phase during the first half of the duration of the total movement is sufficient to generate a turn. The power phase can be followed by a brief gliding phase, and finally the movement appears to be actively terminated.(ABSTRACT TRUNCATED AT 400 WORDS)