bluuebunny/crossref_metadata_2025 huggingface dataset:
Intrinsic organization of the cat's medial geniculate body identified by projections to binaural response-specific bands in the primary auditory cortex
Authors: Middlebrooks JC , Zook JM
Published: March 2018

The area of the cat's primary auditory cortex (AI) within which high frequency sounds are represented can be subdivided using functional criteria. Within each subdivision, or “binaural interaction band,” all recorded neurons display similar responses to binaural stimulation. The current study distinguishes the thalamic sources of input to these subdivisions of AI and characterizes the topography within the thalamic projection to each class of bands. The borders of binaural bands in AI were mapped using microelectrode recording with diotic tonal stimulation, then injections of one to three retrograde tracers were introduced into identified bands. Within the ventral division (V) of the medial geniculate body (the major thalamic source of input to AI), the neuronal populations that projected to different classes of binaural bands were strictly segregated from each other. This segregation of class-specific thalamic sources constitutes a laminar organization within an axis of V that is orthogonal to the previously described tonotopic organization. Excitatory/excitatory (EE) binaural neurons in AI were found to be segregated from excitatory/inhibitory (EI) neurons in alternating “bands.” We consistently identified: (1) a ventral pair of rostrocaudally continuous EI and EE bands, (2) a middle area within which the pattern of binaural subdivisions was more variable and within which bands often were discontinuous rostrocaudally, and (3) a dorsal zone (DZ) within which the responses of neurons differed in binaural properties and in frequency specificity from the response patterns that were characteristic of neurons elsewhere in AI. Each EI band apparently derived input that converged from three thickened laminae of cells in V that were oriented approximately horizontally. The most ventral of these laminae encompassed the ovoidal part of V (Vo), suggesting that EI bands are the only recipients in AI of a projection from Vo. All of the EE bands and DZ derived their input from a single continuous structure which included the dorsal two-thirds of the rostral pole of V and a horizontal lamina interposed between the two dorsalmost EI-projecting laminae. Restricted portions of the complex EE-projecting structure in V projected preferentially to particular EE subdivisions of AI. The V- to-AI thalamocortical topography exhibited a high degree of convergence and divergence within the projections to each cortical binaural band and within the projections to each class of bands. These observations indicate that the high frequency representation in AI and its principal thalamic source of input, the ventral division of the medial geniculate body, may be thought of as assemblies of spatially discrete, functionally distinguishable subunits. The significance of this intrinsic organization is discussed in regard to the requirements for analysis of sound stimuli.
Strychnine blocks binaural inhibition in lateral superior olivary neurons
Authors: Moore MJ , Caspary DM
Published: March 2018

The present study seeks to identify neurotransmitters mediating binaural inhibition in lateral superior olivary nucleus neurons. Neurons in this auditory structure receive inputs from both ears and are thought to code for localization of sound in space. Iontophoretic application of glycine during monaural stimulation was found to mimic the inhibition observed with binaural stimulation. Binaural inhibition was blocked by application of the glycine receptor antagonist, strychnine, as were the effects of iontophoretic application of glycine. The post-strychnine recovery time course for return of synaptically mediated binaural inhibition and recovery of the effects of iontophoretic glycine application were identical. Although the superior olivary complex (SOC) neurons displaying binaural inhibition could in some cases be inhibited by GABA, the binaural inhibition rarely was blocked by iontophoretic application of the GABA receptor antagonist, bicuculline. These findings suggest that glycine may be a neurotransmitter mediating binaural inhibition in certain SOC neurons and that the projection to the lateral superior olivary nucleus from the medial nucleus of the trapezoid body may be glycinergic.
The ultrastructural localization of alpha-bungarotoxin binding sites in relation to synapses on chick ciliary ganglion neurons
Authors: Jacob MH , Berg DK
Published: March 2018

The distribution of alpha-bungarotoxin binding sites on chick ciliary ganglion neurons was examined at the ultrastructural level by incubating ganglia with horseradish peroxidase-conjugated toxin and examining the peroxidase-stained and thin-sectioned ganglia with the electron microscope. Both in embryonic and in adult ganglia heavy labeling was restricted to the surface membrane of short processes emerging from the ciliary and choroid cell somata in the region of preganglionic innervation. Less dense labeling occasionally was present on the smooth surface membrane of the soma in the same region. In contrast, the pre- and postsynaptic membranes of most synapses were clearly not labeled even in the immediate vicinity of heavily labeled processes. The labeling represented specific binding of the toxin conjugate since it could be prevented by d-tubocurarine and hexamethonium or by unconjugated toxin. The conjugated toxin was not excluded from the synaptic cleft on the basis of size because a substantially larger protein conjugate, a horseradish peroxidase- labeled monoclonal antibody, was able to enter the cleft and heavily label synaptic membranes as well as soma membranes. Even neurons in adult ganglia had very little synaptic labeling after exposure to the conjugated toxin. These results strongly suggest that the high affinity alpha-bungarotoxin binding sites on chick ciliary ganglion neurons are different from the synaptic ACh receptors which would be expected to be concentrated in the postsynaptic membrane. Clustering of the alpha- bungarotoxin binding sites in the vicinity of synapses, however, may reflect a related synaptic function.
Regional distribution of calcium- and cyclic adenosine 3':5'- monophosphate-regulated protein phosphorylation systems in mammalian brain. II. Soluble systems
Authors: Walaas SI , Nairn AC , Greengard P
Published: March 2018

The regional distribution of phosphoproteins whose phosphorylation is regulated either by cyclic AMP or by calcium in combination with calmodulin or phospholipid has been investigated in soluble preparations from rat CNS. About 40 distinct phosphoproteins were observed. These cytosolic phosphoproteins exhibited widely different patterns of regional distribution. Based upon distribution patterns, we have divided these phosphoproteins into three categories: category A, phosphoproteins found in all parts of the CNS in approximately equal amounts; category B, phosphoproteins which are widely distributed within the CNS, but which show large regional variations; and category C, phosphoproteins which show a highly restricted regional distribution. We have tentatively interpreted the results on cytosolic phosphoproteins in the following way: some are present in all or nearly all brain cells, others are present only in certain classes of brain cells, and still others have an even more limited distribution, being present in only a single type of brain cell. The regional distribution of soluble protein kinase activity was also studied. Calcium/phospholipid-dependent protein kinase and calcium/calmodulin- dependent protein kinase had marked regional distributions. Cyclic AMP- dependent protein kinase was more evenly distributed throughout the CNS. This investigation thus demonstrates striking differences in the regional distribution of cytosolic protein phosphorylation systems in mammalian brain. These regional differences may reflect highly specific functional roles for certain of these protein phosphorylation systems. Similar conclusions concerning particulate protein phosphorylation systems are described in the preceding paper.
Background and stimulus-induced patterns of high metabolic activity in the visual cortex (area 17) of the squirrel and macaque monkey
Authors: Humphrey AL , Hendrickson AE
Published: March 2018

We have used 2-deoxy-D-[14C]glucose (2-DG) autoradiography and cytochrome oxidase histochemistry to examine background and stimulus- induced patterns of metabolic activity in monkey striate cortex. In squirrel monkeys (Saimiri sciureus) that binocularly or monocularly viewed diffuse white light or binocularly viewed bars of many orientations and spatial frequencies, 2-DG consumption was not uniform across the cortex but consisted of regularly spaced radial zones of high uptake. The zones extended through all laminae except IVc beta and, when viewed tangentially, formed separate patches 500 microns apart. The cytochrome oxidase stain in these animals also revealed patches of high metabolism which coincided with the 2-DG patches. Squirrel monkeys binocularly viewing vertical stripes showed parallel bands of increased 2-DG uptake in the cortex, while the cytochrome label in these animals remained patchy. When monkeys were kept in the dark during 2-DG exposure, 2-DG-labeled patches were not seen but cytochrome oxidase-positive patches remained. In macaque (Macaca nemestrina) monkeys, binocular stimulation with many orientations and spatial frequencies produced radial zones of high 2-DG uptake in layers I to IVa and VI. When viewed tangentially, these zones formed a dots-in- rows pattern with a spacing of 350 X 500 microns; cytochrome oxidase staining produced an identical pattern. Macaca differed from Saimiri in that monocular stimulation labeled alternate rows. These results indicate that there are radial zones of high background metabolism across squirrel and macaque monkey striate cortex. In Saimiri these zones do not appear to be related to an eye dominance system, while in Macaca they do. The presence of these zones of high metabolism may complicate the interpretation of 2-DG autoradiographs that result from specific visual stimuli.
Monoclonal antibodies demonstrate the organization of axons in the leech
Authors: Hockfield S , McKay R
Published: March 2018

Monoclonal antibodies have been generated that bind to subsets of neurons within the leech central nervous system (Zipser, B., and R. McKay (1981) Nature 289: 549–554). In this report we describe the binding patterns of monoclonal antibodies to subsets of axons in the leech using HRP-immunohistochemistry. Each antibody has a characteristic staining pattern in the connective, the large bundle of axons that runs the length of the nerve cord connecting each ganglion to its rostral and caudal neighbors. These staining patterns are consistent along the rostrocaudal axis of each animal, between animals of the same species, and, in many cases, between animals of different species. These results show that axonal position, like neuron cell body position, is a consistent feature of the organization of the leech central nervous system. Two antibodies bind to all of the axons in particular fascicles that are delimited by glial cell processes; another binds to single axons in fascicles that contain other, unstained axons. The grouping of antibody-identified axons into fascicles does not correlate in a simple way with the grouping of neuron cell bodies identified with the same antibody. The presence of one of these antigens on the surface of axons suggests a possible role in axon fasciculation. This report shows that molecular heterogeneity is a property of axons as well as of neuron cell bodies and demonstrates the organization of specific antibody-identified groups of axons within the connective.
Hormonal control of a developing neuromuscular system. I. Complete Demasculinization of the male rat spinal nucleus of the bulbocavernosus using the anti-androgen flutamide
Authors: Breedlove SM , Arnold AP
Published: March 2018

Prenatal treatment of male rats with the anti-androgen, flutamide (FL), demasculinizes the sexually dimorphic spinal nucleus of the bulbocavernosus (SNB) by reducing the number of SNB neurons, the size of the somas and nuclei of SNB neurons, and the size of their target muscles in adulthood. However, FL does not affect mounting or the traditional, postural measure of intromission, indicating that the SNB system does not play a major role in the mediation of these particular behaviors. Postnatal testosterone propionate (TP) treatment of male rats castrated on the day of birth results in more male copulatory behaviors in adulthood and masculinizes all measures of the SNB system. The postnatal masculinization by TP is more pronounced in males treated prenatally with FL, for morphological but not behavioral measures. The combined treatment of prenatal FL and day 1 castration without TP therapy results in a male with a completely demasculinized SNB system. Specifically, such males have SNB neurons that are as scarce and as small as those of females and, like females, they lack the target muscles of the SNB. These results support the hypothesis that perinatal androgens normally direct the sexually dimorphic development of the SNB and its target muscles.
Photoaffinity labeling of benzodiazepine receptors causes altered agonist-antagonist interactions
Authors: Thomas JW , Tallman JF
Published: March 2018

Previous studies have shown that [3H]flunitrazepam forms irreversible cross-links with brain tissue when exposed to ultraviolet irradiation. Comparison of the amount of [3H]flunitrazepam irreversibly incorporated and the number of benzodiazepine binding sites blocked after photolabeling has indicated that several binding sites are inactivated for each molecule of [3H]flunitrazepam incorporated. To learn the cause of this discrepancy, binding to the benzodiazepine binding sites has been examined using several radiolabeled benzodiazepine antagonists. Binding of a beta-carboline ester, CGS-8216, and Ro 15–1788 was not altered by photolabeling; however, displacement studies revealed that photolabeling converted a homogeneous set of benzodiazepine binding sites into two subsets: one of high affinity (unaltered sites) and one of low affinity. The low affinity sites could be detected by displacement studies of antagonist binding by benzodiazepines, and conversion to a low affinity form accounts for the discrepancy observed after photolabeling using [3H]flunitrazepam as ligand.
Song structure without auditory feedback: emendations of the auditory template hypothesis
Authors: Marler P , Sherman V
Published: March 2018

Motor patterns of songs of swamp and song sparrows, Melospiza georgiana and M. melodia, deafened early in life display a significant degree of species-specific structure. Normal songs of the two species differ in the degree to which they are segmented. Swamp sparrow song consists of a single segment, and song sparrow songs are multisegmental. Song and swamp sparrows were deafened at 17 to 23 days, prior to the onset of song or subsong. The song sparrows developed more segments in their singing than the swamp sparrows. Species-specific trends were also evident in song durations and frequency characteristics. Abnormalities were found, however, in the morphology of the notes and syllables from which songs of early deafened sparrows are constructed. These results require emendation of the auditory template hypothesis of song learning in birds.
Chemical characteristics of the L-glutamate receptor on the Onchidium neuron
Authors: Kato M , Oomura Y , Maruhashi J , Shimizu N
Published: March 2018

Application of L-glutamate (L-glu) to particular neurons (G-H cells) in the esophageal ganglia of Onchidium produced hyperpolarization associated with an increase in K+ permeability. The reversal potential (Erev) for this response, was -60 mV. The ED50, an indicator of affinity between L-glu and its receptive site, was 5.3 mM, and the Hill coefficient n, an indicator of cooperativity, was 2. Other chemicals, structurally analogous to L-glu, were also examined on G-H cells. The responses of L-aspartate were similar to those of L-glu with respect to Erev, ED50, and n. However, the G-H cells responded differently to D- glutamate (D-glu) and kainic acid. The D-glu response had an Erev = - 37.5 mV, ED50 = 29.4 mM, and n = 1; that of kainic acid had an Erev = 0 mV, ED50 = 1.5 mM, and n = 1. L-glutamine and GABA elicited very small responses, amplitudes of which were less than 10% of the L-glu response. The structure-activity relationship between L-glu and its analogues, estimated from Erev, ED50, and Hill coefficient during each drug application, indicates that the presence of alpha-NH2, alpha-COOH, and gamma-COOH groups is essential for the L-glu response and that the response characteristics may be closely related to the relative positions of these groups.
Microtubule-neurofilament segregation produced by beta, beta'- iminodipropionitrile: evidence for the association of fast axonal transport with microtubules
Authors: Griffin JW , Fahnestock KE , Price DL , Hoffman PN
Published: March 2018

The subperineurial injection of beta,beta'-iminodipropionitrile (IDPN) into rat sciatic nerves resulted in focal disorganization of the axonal cytoskeleton characterized by segregation of neurofilaments and microtubules. Shortly after injection, microtubules clustered together to form a central channel, while neurofilaments became chaotically arrayed between the microtubule channel and axolemma. Electron microscopic autoradiography disclosed that rapidly transported organelles were preferentially associated with the microtubule-enriched central channels. These studies indicate that IDPN acts at the level of the axon to disrupt interactions between cytoskeletal elements and show that rapidly transported constituents are preferentially conveyed in association with microtubules. The model provides an opportunity to dissect the interactions of the cytoskeletal elements and other organelles.
Mapping of serotonin-like immunoreactivity in the lobster nervous system
Authors: Beltz BS , Kravitz EA
Published: March 2018

Serotonin exerts a wide range of physiological actions on many different lobster tissues. To begin the examination of the role of serotonin in lobsters at a cellular level, we have used immunohistochemical methods to search for presumptive serotonergic neurons, their central and peripheral projections, and their terminal fields of arborization. Whole mount preparations of the ventral nerve cord and various peripheral nerve structures have been used for these studies. With these tissues, more than 100 cell bodies have been found that show serotonin-like immunoreactivity. Although a few of the cell bodies are located peripherally (near the pericardial organs, a well known crustacean neurohemal organ), the vast majority are located in central ganglia. Every ganglion in the ventral nerve cord contains at least one immunoreactive cell body. The projections of many of the neurons have been traced, and we have constructed a map of the system of serotonin-immunoreactive cell bodies, fibers, and nerve endings. In addition, a dense plexus of nerve endings showing serotonin-like immunoreactivity surrounds each of the thoracic second roots in the vicinity of groups of peripheral neurosecretory neurons. These peripheral nerve plexuses originate from central neurons of the ventral nerve cord. In some cases we have been able to trace processes from particular central cell bodies directly to the peripheral nerve root plexuses; in other cases we have traced ganglionic neuropil regions to these peripheral endings.
Developmental factors affecting regeneration in the central nervous system: early but not late formed mitral cells reinnervate olfactory cortex after neonatal tract section
Authors: Grafe MR
Published: March 2018

If the lateral olfactory tract (LOT) of the golden hamster is transected in the first week of postnatal life, axons will grow back through the cut and reinnervate the terminal regions. Functional recovery occurs only when the terminal regions are reinnervated. The experiments reported here tested the hypothesis that reinnervation is due to neogenesis: the continued growth of newly formed axons which were not severed by the lesion. In the first experiment the birth dates of the mitral and tufted cells were determined in the hamster. It was found that mitral cells are formed on gestational days 11 and 12 (E11 and E12) and tufted cells on E11 to E14. Experiment 2 involved the combination of [3H]thymidine labeling, for the time of cell formation, with the retrograde transport of horseradish peroxidase (HRP), at a time when the LOT projections are not yet complete. The axons of early formed cells were found to reach the olfactory cortex before those of later formed cells. Experiment 3 examined the possibility that the axons which grow through an early LOT transection are new axons that had not yet reached the level of the cut. Animals were given [3H]thymidine to label the times of formation of mitral and tufted cells and then were given a transection of the LOT on postnatal day 3 (P3). After a recovery period sufficient to allow axonal regrowth and reinnervation, HRP was placed in the olfactory projection region caudal to the prior LOT section. The original hypothesis was not supported. Cells that are formed early and send out their axons early are able to reinnervate the olfactory cortex, whereas late formed cells do not. The results of this experiment suggest that the factors which prevent the regrowth of axons when the LOT is cut after P7 may depend on the stage of development of the tissue into which the axons are growing, rather than in the cells of origin and their axons.
Transplantation of cricket sensory neurons to ectopic locations: arborizations and synaptic connections
Authors: Murphey RK , Bacon JP , Sakaguchi DS , Johnson SE
Published: March 2018

The cerci (abdominal sensory appendages) of crickets were transplanted to a leg stump after amputating the leg. Single identifiable cercal afferents were stained and found to regenerate into the host thoracic ganglia. A given neuron always arborizes in the same area of neuropil of the foreign ganglion and is distinctive in this property from other identified neurons. Taken as a whole, the results show that the afferents from the ectopic cercus are spatially ordered, the destination of a particular afferent within the ganglion being correlated with the location of its sensory cell body on the cercal surface. This is the case for the pro-, meso-, and metathoracic ganglion and the topography of these ectopic projections bears some resemblance to the normal projections found in the terminal ganglion. Thus the insect segmental ganglion seems to possess a set of markers which are interpretable by all afferent neurons, and this organization is repeated in each ganglion. The ectopic afferents make functional synaptic connections with intersegmental interneurons, one of which is described anatomically here. However, the ectopic afferents do not, as had previously been reported, make functional connections with the medial giant or lateral giant interneuron (the normal targets of cercal sensory neurons in the terminal ganglion).
Activation of beta 2-adrenergic receptors on mouse anterior pituitary tumor cells increases cyclic adenosine 3':5'-monophosphate synthesis and adrenocorticotropin release
Authors: Reisine TD , Heisler S , Hook VY , Axelrod J
Published: March 2018

AtT-20 cells comprise a mouse anterior pituitary tumor cell line that synthesizes and secretes adrenocorticotropin hormone (ACTH). beta- Adrenergic receptors were characterized on AtT-20 cells using receptor binding methodology and the ability of beta-receptor agonists to stimulate intracellular cyclic adenosine 3′:5′-monophosphate (cAMP) formation and the release of ACTH immunoreactivity. The density of beta- receptors on membrane preparations of these cells is 64 fmol/mg of protein and their affinity constant (KD value) for tritiated dihydroalprenolol is 11 nM. The binding of [3H] dihydroalprenolol to AtT-20 cells is stereoselectively inhibited by propranolol and isoproterenol but is not affected by phentolamine. The beta-receptors on these cells appear to be of the beta 2-receptor subtype since a selective beta 2-receptor agonist, salmefamol, can inhibit [3H]dihydroalprenolol binding, whereas practolol, a beta 1-receptor blocker, is ineffective. (-)-Isoproterenol stimulates cAMP formation in AtT-20 cells and this effect is blocked by dl-propranolol. Both l- epinephrine and l-norepinephrine induce dose-dependent increases in cAMP formation with the former agonist being more potent. Salmefamol also stimulates cAMP formation in these cells. The secretion of ACTH from AtT-20 cells is induced by (-)-isoproterenol as well as by other adrenergic agonists. The isoproterenol effect on ACTH release is stereoselective, calcium dependent, and blocked by dl-propranolol but not by phentolamine or practolol.
The effect of cortical lesions on the electromyographic response to joint displacement in the squirrel monkey forelimb
Authors: Lenz FA , Tatton WG , Tasker RR
Published: March 2018

The extent of participation of supraspinal structures in the generation of the long latency (M2) electromyographic (EMG) response to imposed joint displacement may be reflected in the effect of lesions of the central nervous system. M2 activity has been reported in a variety of studies to be either present or absent following supraspinal lesions. Since other studies have shown different characteristics of long latency activity in proximal as compared to distal upper limb muscles in primates, the present experiments were conducted to determine the effect of motor cortical (area 4) lesions on reflex activity generated in a proximal versus a distal upper limb muscle. Chronic experiments were performed on squirrel monkeys with unilateral lesions of the forelimb motor cortex (area 4) which was mapped with the aid of electrical stimulation. Input-output relationships were determined between torque motor-imposed joint rotation and the EMG response in the stretched muscles (flexor digitorum profundus (FDP) and short head of biceps (SHB)). The EMG responses were reported as a percentage of maximum EMG output and controlled for base line EMG level. The “gain” (slope of EMG response versus torque load) for FDP M2 activity was markedly decreased in the limb contralateral to the area 4 lesion as compared to the opposite limb. This decrease was independent of base line EMG levels. In SHB, early latency (M1) EMG activity was significantly increased, but M2 activity appeared unaffected on the side contralateral to the lesion. The results demonstrate that the central and peripheral mechanisms generating M2 activity in FDP differ from those in SHB in terms of motor cortical dependency.
Variations in number of dopamine neurons and tyrosine hydroxylase activity in hypothalamus of two mouse strains
Authors: Baker H , Joh TH , Ruggiero DA , Reis DJ
Published: March 2018

Mice of the BALB/cJ strain have more neurons and greater tyrosine hydroxylase (TH) activity in the midbrain than mice of the CBA/J strain (Baker, H., T. H. Joh, and D. J. Reis (1980) Proc. Natl. Acad. Sci. U.S.A. 77: 4369–4373). To determine whether the strain differences in dopamine (DA) neuron number and regional TH activity are more generalized, regional TH activity was measured and counts of neurons containing the enzyme were made in the hypothalamus of male mice of the BALB/cJ and CBA/J strains. TH activity was measured in dissections of whole hypothalamus (excluding the preoptic area), the preoptic area containing a rostral extension of the A14 group, the mediobasal hypothalamus containing the A12 group, and the mediodorsal hypothalamus containing neurons of the A13 and A14 groups. Serial sections were taken and the number of DA neurons was established by counting at 50- to 60-microns intervals all cells stained for TH through each area. In conjunction with data obtained biochemically, the average amount of TH per neuron was determined. In all areas, TH activity in CBA/J mice was significantly less (p less than 0.001) than in BALB/cJ mice, ranging from 48% in the mediobasal hypothalamus to 71% in the medial and dorsal hypothalamus. The number of TH-containing neurons was also significantly less in the CBA/J strain (p less than 0.001), ranging from 49% in the preoptic area to 74% in the mediobasal hypothalamus (MBH). With the exception of the MBH, enzyme activity per neuron was similar in both strains. In the MBH, strain differences in TH activity were greater than those for neuron number, resulting in less TH activity per neuron in the CBA/J strain. The results suggest that strain differences in the number of DA neurons are widespread and involve DA systems throughout the brain. Therefore, differences in whole brain TH activity cannot be attributed only to differences in specific regions. Our findings further support the view that the number of neurons of a specific chemical class may be under genetic control.
Circadian rhythms in the Limulus visual system
Authors: Barlow RB
Published: March 2018

A circadian clock in the Limulus brain generates efferent optic nerve activity at night. The endogenous activity begins near dusk, continues during the night, and stops near dawn. Approximately 10 to 20 efferent fibers in each lateral optic nerve trunk fire in close synchrony with one another and with the efferent fibers in the opposite nerve trunk producing bursts of nerve impulses at night. The synchronous bursting activity indicates extensive coupling in the brain among the efferent neurons or among the circadian pacemakers that drive them. The efferent optic nerve activity mediates circadian rhythms in retinal responses. Electroretinograms (ERGs) from both the lateral eyes and median ocelli exhibit circadian rhythms of equal phase. Sectioning the optic nerves abolishes the rhythms. When the animal is kept in darkness, the phase of the rhythm can be shifted by illuminating the lateral eyes but not the median ocelli. The endogenous rhythm persists for at least 1 year in darkness without attenuation and without substantial changes in the circadian period. Across a large population of animals the duration of the circadian period ranges from 22.2 to 25.5 hr, with a mean value of 23.9 +/- 0.7 hr (n = 75). The nighttime increase in ERG amplitude represents a 20- to 100-fold increase in retinal sensitivity. Most of the increased sensitivity results from an increase in the number of photons absorbed by the photoreceptors at night. A small component may be due to an increase in gain. Pulses of current delivered to the lateral optic nerve during the day mimic the effects of endogenous efferent activity and transform the eye to the nighttime state. The Limulus visual system has evolved numerous mechanisms for adapting visual sensitivity to daily fluctuations in the photic environment. A key to understanding the organization of the visual system is the circadian clock and its associated neural circuitry.
Autoradiographic localization of cholecystokinin receptors in rodent brain
Authors: Zarbin MA , Innis RB , Wamsley JK , Snyder SH , Kuhar MJ
Published: March 2018

Cholecystokinin (CCK) receptor binding sites have been localized by autoradiography in the guinea pig and rat central nervous system. [125I]CCK-triacontatriapeptide labeled the sites in brain slices with an observed association constant equal to 0.041 min-1 and a dissociation constant equal to 0.008 min-1. CCK-triacontatriapeptide (CCK-33) and the C-terminal octapeptide of CCK-33 (CCK-8) potently inhibited [125I]CCK-33 binding with Ki's of 2 nM, whereas desulfated CCK-8 (CCK8-ds) and the C-terminal tetrapeptide of CCK-33 (CCK-4) were much weaker. Receptors were concentrated in the olfactory bulb, in the superficial laminae of the primary olfactory cortex, in the deep laminae of the cerebral cortex, and in the pretectal area. Substantial numbers of sites were also found in the basal ganglia, in the amygdala, and in the hippocampal formation. [125I]CCK-33 binding sites appear to be located on fibers of the optic tract and probably on olfactory tract fibers as well. These results are discussed in terms of physiological functions associated with CCK, presynaptic receptors, and axonal flow of CCK receptors.
Effects of somatostatin on mammalian cortical neurons in culture: physiological actions and unusual dose response characteristics
Authors: Delfs JR , Dichter MA
Published: March 2018

Somatostatin was applied to rat cortical neurons grown in dispersed cell culture while electrophysiological effects were monitored with intracellular recordings. The effects of somatostatin were predominantly excitatory, but they varied and were dose dependent. Somatostatin at concentrations between 100 pM and 1 microM depolarized 30 of 87 neurons, often with a concomitant increase in spontaneous action potentials and a small increase in membrane input resistance. Somatostatin also increased the frequency of synaptic activity coming into the recorded neuron in 45 of 78 recordings, an effect which was seen even in the absence of direct effects. In six of nine neurons, somatostatin decreased the amplitude of large ongoing inhibitory synaptic potentials, concomitant with an increase in membrane input resistance. Somatostatin occasionally caused inhibition of neuronal activity, an effect predominantly associated with the application of higher concentrations. The unpredictability of the response of an individual neuron to somatostatin is partially explained by three phenomena: a marked tachyphylaxis, an inverted U-shaped dose response curve for membrane depolarization, and qualitatively different responses depending on the concentration of somatostatin. These findings show that somatostatin is predominantly an excitatory agent when applied to cortical neurons, but it may cause several different changes in membrane properties. The dose response data suggest a considerable complexity of the actions of somatostatin at a cellular level.
Neural pathway constraints in the motor innervation of the chick hindlimb following dorsoventral rotations of distal limb segments
Authors: Whitelaw V , Hollyday M
Published: March 2018

Several studies have demonstrated that motor axons can discriminate between dorsally and ventrally derived muscles. In this paper we present evidence that (1) the pathway axons take in the limb constrain their access to either dorsally or ventrally derived muscles, and therefore (2) the axon's ability to discriminate between dorsal and ventral is expressed already at the level of pathway selection into the limb. Surgically manipulated hindlimbs were produced consisting of a normal host thigh connected to a dorsoventrally rotated calf or to rotated and duplicated donor limb segments. The limb rotations were done distal to the level at which axons select a dorsally or ventrally destined pathway through the limb, such that at the level of the rotation, axons in each nerve were confronted with the opposite-from- normal set of muscles. In this situation, the relative influence of pathway availability versus dorsal/ventral muscle recognition could be assessed. The innervation of rotated limb segments was, in all cases, opposite from normal. Motoneurons which normally innervate dorsal muscles innervated ventrally derived muscles that had been rotated into a dorsal position. Likewise, normally ventrally destined axons served dorsal muscles in the rotated segments. Thus, motor axons did not alter their distal path to reach their normal set of muscles. While these results do not rule out intrinsic dorsal/ventral differences between muscles, they do demonstrate that muscle surface recognition is not necessary to account for dorsal/ventral discrimination in the innervation of normal, supernumerary, or duplicated limbs, nor is it sufficient to account for the innervation of rotated limb segments. These results also indicate that pathway guidance cues are an important influence on innervation patterns.
Two types of astrocytes in cultures of developing rat white matter: differences in morphology, surface gangliosides, and growth characteristics
Authors: Raff MC , Abney ER , Cohen J , Lindsay R , Noble M
Published: March 2018

Two types of glial fibrillary acidic protein-positive (GFAP+) astrocytes were found in cultures of developing rat optic nerve. Type 1 astrocytes had a fibroblast-like morphology, did not bind tetanus toxin or the monoclonal antibody A2B5 (both of which bind to specific polysialogangliosides), and were stimulated to divide by an extract of bovine pituitary and by epidermal growth factor (EGF). Type 2 astrocytes had a neuron-like morphology, bound tetanus toxin and A2B5 antibody, and were not stimulated to divide by bovine pituitary extract or by EGF. Although both types of astrocytes were present in cultures of white matter, only type 1 astrocytes were found in cultures of gray matter. Astrocytes did not convert from one type to the other in culture: while many type 1 astrocytes adopted a neuron-like morphology when exposed to dibutyryl cyclic adenosine 3′:5′-monophosphate, or pituitary or brain extracts, especially in serum-free medium, such morphologically altered cells did not bind tetanus toxin or A2B5 antibody. Although small numbers of tetanus toxin-binding, A2B5+, GFAP+ cells were present in suspensions of freshly dissected, neonatal optic nerves, most of the type 2 astrocytes in cultures of such optic nerves developed from tetanus toxin-binding, A2B5+, GFAP- cells, which were induced to express GFAP by the culture conditions. Since type 2 astrocytes have a neuron-like morphology and bind tetanus toxin and A2B5 antibody, these ligands cannot be used on their own as neuron- specific markers in central nervous system cultures.
Cooperativity among afferents for the induction of long-term potentiation in the CA1 region of the hippocampus
Authors: Lee KS
Published: March 2018

Long-term potentiation of synaptic responses in the hippocampus is a unique form of physiological plasticity which can be induced by brief episodes of repetitive afferent activity and which can persist for days or months. The present study describes cooperative (or associative) interactions among afferents to the stratum radiatum of CA1 for the induction and maintenance of this phenomenon. A greater degree of long- term potentiation was obtained when adjacent afferents to the stratum radiatum were co-actively conditioned, as compared to that observed with activation of a single pathway alone. This cooperativity was not the result of increased postsynaptic discharge during conditioning, as shown by the absence of greater long-term potentiation following orthodromic and antidromic co-activation of the postsynaptic CA1 pyramidal cells.
The timing of protein synthesis required for the development of the sodium action potential in embryonic spinal neurons
Authors: Blair LA
Published: March 2018

Embryonic amphibian neurons grown in dissociated cell culture extend neurites and can produce action potentials. The ionic dependence of the inward current of the action potential gradually changes from primarily calcium to primarily sodium. Early exposure of these neurons to protein synthesis inhibitors (cycloheximide, puromycin) blocked the appearance of neurites; later exposure blocked the normal change in the ionic basis of the action potential. These drugs apparently arrested the development of the sodium component of the action potential and, additionally, may have blocked a reduction in the calcium component. Inhibitor applied at still later times did not prevent the normal development of these traits. The development of voltage-sensitive delayed rectification was unaffected by the addition of inhibitor at any of the times tested.
Acoustic chiasm: efferent projections of the lateral superior olive
Authors: Glendenning KK , Masterton RB
Published: March 2018

The efferent connections of the cat's lateral superior olive (LSO) were examined first with kainic acid-induced anterograde degeneration and tritiated leucine autoradiography and then by systematic repetition of HRP and fluorescent dye retrograde tract-tracing techniques. The results show that virtually all LSO cells have axons ascending either contralaterally or ipsilaterally to high pontine and midbrain levels of the brainstem. Most terminate in the ventrolateral division of either the ipsilateral or contralateral central nucleus of the inferior colliculus, some terminate in the ipsilateral or contralateral dorsal nucleus of the lateral lemniscus, and a small number terminate in the ipsilateral intermediate nucleus of the lateral lemniscus. Only a small proportion (less than 5%) of LSO cells project to both sides via axon collaterals. The ipsilateral, contralateral, and bilateral projections arise from three overlapping subpopulations of cells within LSO: Those projecting ipsilaterally are concentrated in its lateral limb; those projecting contralaterally are concentrated in its medial limb; the few projecting bilaterally are thinly scattered throughout. Therefore, a lateral-medial gradient is present across LSO based on the laterality of its cell's efferent targets. This gradient parallels LSO's tonotopic gradient: The higher the characteristic frequency of an LSO cell, the more likely it is to project contralaterally. This arrangement of LSO's ascending projections, with most of its lateral cells projecting ipsilaterally and most of its medial cells projecting contralaterally, is similar to the arrangement of the optic chiasm in animals with overlapping eye-fields. Its presence seems to provide an anatomical basis for some recent electrophysiological and behavioral reports of chiasm-like properties of the superior olivary complex.
Increased sodium ion conductance through nicotinic acetylcholine receptor channels in PC12 cells exposed to nerve growth factors
Authors: Amy CM , Bennett EL
Published: March 2018

22Na+ uptake in response to cholinergic stimulation was measured in PC12 cells grown in media containing either beta-nerve growth factor (NGF) from mouse submaxillary gland or a component of Bungarus multicinctus venom (fraction 9B) which has nerve growth factor activity. Our results showed that each of these nerve growth factors increased the Na+ conductance capacity of ACh receptor-linked ion channels in PC12 cells. Compared to untreated cells, Na+ uptake was enhanced by about 40% in cells exposed for 24 to 30 hr to either 50 ng/ml of beta-NGF or to 5 micrograms/ml of fraction 9B. This cholinergically stimulated Na+ flux increased with time and reached a level 2- to 3-fold higher than that of untreated cells after 4 to 6 days' exposure to NGFs. The generation of neurites in response to NGFs from either source occurred with the same time course as the increase in Na+ channel conductance. Growth factor-enhanced Na+ uptake remained for several days after NGFs were removed from cells and neurites were lost. Na+ flux into untreated and into 9B- or beta-NGF-treated cells was inhibited to a greater extent by a nicotinic than by a muscarinic antagonist. Dibutyryl cyclic AMP did not cause an increase in Na+ uptake in response to cholinergic agonists at concentrations which stimulated neurite-like process formation, and dibutyryl cyclic AMP did not potentiate the effects of NGFs.
Relations between parameters of step-tracking movements and single cell discharge in the globus pallidus and subthalamic nucleus of the behaving monkey
Authors: Georgopoulos AP , DeLong MR , Crutcher MD
Published: March 2018

We describe the relations between the direction, amplitude, and velocity of step-tracking arm movements and the frequency of single cell discharge in the external (GPe) and internal (GPi) segments of the globus pallidus and the subthalamic nucleus (STN) of the behaving monkey. Statistically significant relations to the direction, amplitude, and peak velocity of the movement were found in all structures studied predominantly during the movement but also during the reaction time. For movements in a particular direction, the discharge rate was frequently a linear function of the movement amplitude and/or peak velocity. The slopes of this relation differed for different cells and comprised both positive and negative values. STN differed from both GPe and GPi in that (a) a larger proportion of neurons in STN showed significant relations to the direction of movement and (b) the onset times of changes in neural activity related to movement occurred earlier in STN than in GPe or GPi. The results of these studies suggest that cells in GPe, GPi, and STN may be involved in the control of movement parameters. Loss of the basal ganglia output related to the amplitude or velocity of movement might account for the impairments of step movements observed in Parkinsonian patients. On the other hand, deranged or excessive output related to amplitude or velocity control might result in the excesses of movement observed in other disorders, such as chorea and hemiballismus. These studies also provide direct evidence that the STN exerts a specific influence on basal ganglia output related to the control of movement parameters.
Typical and atypical neuroleptics: differential effects of chronic administration on the activity of A9 and A10 midbrain dopaminergic neurons
Authors: Chiodo LA , Bunney BS
Published: March 2018

Extracellular single unit recording techniques were used to study the effects of both acute and repeated oral neuroleptic administration on the in vivo activity of rat A9 and A10 dopaminergic (DA) neurons. All antipsychotic drugs examined acutely (haloperidol, l-sulpiride, chlorpromazine, and clozapine) increased the number of spontaneously firing DA neurons in both A9 and A10 compared to controls. Repeated (21 day) treatment with haloperidol, l-sulpiride, and chlorpromazine (antipsychotic drugs which can cause extrapyramidal side effects) markedly reduced the number of active DA cells below control levels in both regions. The “silent” DA neurons were in an apparent state of tonic depolarization inactivation since they could be induced to discharge by the microiontophoretic application of the inhibitory neurotransmitter gamma-aminobutyric acid, but not the excitatory amino acid glutamate. The depolarization inactivation observed may be specific for antipsychotic drugs since a non-neuroleptic phenothiazine (promethazine), the inactive isomer of sulpiride (d-sulpiride), and a tricyclic antidepressant (desmethylimipramine) neither increased DA activity when given acutely nor induced depolarization inactivation when administered repeatedly. In contrast to the other drugs tested, repeated treatment with clozapine (an effective antipsychotic drug which does not produce extrapyramidal side effects) resulted in the depolarization inactivation of A10 neurons but not A9 cells. These data suggest that neuroleptics which can induce extrapyramidal side effects produce depolarization inactivation of both A9 and A10 neurons whereas antipsychotic drugs which lack this property inactivate only A10 neurons. It is suggested that the time-dependent development of A9 DA neuron inactivation induced by repeated neuroleptic treatment may provide a mechanism for understanding the delayed onset of extrapyramidal side effects often observed with these drugs.