bluuebunny/crossref_metadata_2025 huggingface dataset:
Single unit analysis of the human ventral thalamic nuclear group: correlation of thalamic "tremor cells" with the 3-6 Hz component of parkinsonian tremor
Authors: Lenz FA , Tasker RR , Kwan HC , Schnider S , Kwong R , Murayama Y , Dostrovsky JO , Murphy JT
Published: March 2018

Although cells firing at tremor frequency, called “tremor cells” (Guiot et al., 1962), have often been recorded in the thalamus of parkinsonian patients, the extent of correlation between these spike trains and tremor has rarely been assessed quantitatively. This paper describes spectral cross-correlation functions calculated between the activity of “tremor cells” and electromyogram (EMG) signals recorded from several muscles in the contralateral arm. The power occurring in the spike train at tremor frequency was described in absolute terms by the spike autopower, and in relation to the average for all spectral components by the spike autopower signal-to-noise ratio (spike autopower SNR). The probability of significant cross-correlation between the thalamic spike train and EMG at tremor frequency was assessed by the coherence at tremor frequency. Autopower spectra of the activity of many of these cells exhibited a concentration of power at tremor frequency, indicated by spike autopower SNRs as high as 18. Of the EMG signals studied, signals recorded from finger flexors were most often significantly correlated at tremor frequency. Significant correlation between the thalamic spike train and finger flexor EMG activity was found in 34% of cells analyzed. Tremor frequency coherence was significantly correlated with tremor frequency spike autopower (r = 0.46, p less than 0.0001) and spike autopower SNR (r = 0.533, p less than 0.0001). The proportion of cells with a spike autopower SNR greater than 2 that were significantly correlated with finger flexor EMG activity was greater than that of cells with a spike autopower SNR of less than 2 (p less than 0.001; chi-square). Therefore, cells exhibiting a large amount of power at tremor frequency were those best correlated with EMG activity during tremor. Some of these cells may be involved in the generation of tremor.
Development of voltage-dependent calcium, sodium, and potassium currents in Xenopus spinal neurons
Authors: O'Dowd DK , Ribera AB , Spitzer NC
Published: March 2018

Action potentials of embryonic nerve and muscle cells often have a different ionic dependence and longer duration than those of mature cells. The action potential of spinal cord neurons from Xenopus laevis exhibits a prominent calcium component at early stages of development that diminishes with age as the impulse becomes principally sodium dependent. Whole-cell voltage-clamp analysis has been undertaken to characterize the changes in membrane currents during development of these neurons in culture. Four voltage-dependent currents of cells were identified and examined during the first day in vitro, when most of the change in the action potential occurs. There are no changes in the peak density of the calcium current (ICa), its voltage dependence, or time to half-maximal activation; a small increase in inactivation is apparent. The major change in sodium current (INa) is a 2-fold increase in its density. In addition, more subtle changes in the kinetics of the macroscopic sodium current were noted. The peak density of voltage- dependent potassium current (IKv) increases 3-fold, and this current becomes activated almost twice as fast. No changes were noted in the extent of its inactivation. The calcium-dependent potassium current (IKc) consists of an inactivating and a sustained component. The former increases 2-fold in peak current density, and the latter increases similarly at less depolarized voltages. The changes in these currents contribute to the decrease in duration and the change in ionic dependence of the impulse.
Expression of NGF receptor in the developing and adult primate central nervous system
Authors: Schatteman GC , Gibbs L , Lanahan AA , Claude P , Bothwell M
Published: March 2018

Monoclonal antibodies against human NGF receptor have been used for immunocytochemical localization of NGF receptors in the CNS of macaques and baboons at various stages of development. In the adult, neurons in most brain regions are devoid of detectable NGF receptors. However, abundant NGF receptor immunoreactivity is present on a population of neurons in basal forebrain, which, on the basis of appearance and pattern of distribution, probably correspond, at least in part, to magnocellular cholinergic neurons of this region. NGF receptors were also associated with the vasculature in most brain regions. NGF receptor immunoreactivity is present on Mueller glia of neural retina. In macaque fetuses, approximately 1 month prenatally, retinal Mueller glia possess lower levels of receptor, while higher levels of receptor are present in the retinal nerve fiber layer. In fetal cerebellum, abundant receptor immunoreactivity is present on Purkinje cells, granule cells of the premigratory zone of the external granule layer, and neurons of the deep nuclei. Immunoreactivity decreases with subsequent development and is absent in the adult. In cerebellum, levels of NGF receptor assayed by affinity crosslinking to radioiodinated NGF, and levels of NGF receptor mRNA assayed by Northern blot analysis decrease dramatically during the last month of fetal life.
Genesis of GABA-immunoreactive neurons in the ferret visual cortex
Authors: Peduzzi JD
Published: March 2018

The pattern of neurogenesis of GABA-immunoreactive neurons in the ferret primary visual cortex was determined using immunohistochemical and 3H-thymidine autoradiographic techniques. Neurons in the visual cortex of the ferret undergo their final cell division during a period extending from embryonic day 20 (E20) to postnatal day 14 (P14) and follow an inside-out pattern of neuronal production (Jackson et al., 1984) similar to that observed in other mammals. Earlier-generated neurons are found at deeper cortical positions in the adult than are those generated later. Layer I is an exception to this rule, since neurons destined for this layer are produced at both the beginning and end of neurogenesis. In this study, the pattern of neurogenesis of GABA- immunoreactive neurons is compared to the pattern observed for nonimmunoreactive neurons. The overall pattern of cortical neurogenesis (inside-out pattern) is similar for GABA-immunoreactive neurons and neurons that are not GABA-immunoreactive. However, the GABA- immunoreactive neurons born on a given day of development are more broadly distributed across the radial axis of the adult cortex than are nonimmunoreactive neurons generated on the same day. GABA- immunoreactive neurons generated later in neurogenesis are, on average, slightly smaller than those generated early. If GABA-immunoreactive neurons in the visual cortex are interneurons, then these findings suggest that interneurons follow the same pattern of neurogenesis as do projecting neurons in the visual cortex.
Corticotropin-releasing hormone increases tonic but not sensory-evoked activity of noradrenergic locus coeruleus neurons in unanesthetized rats
Authors: Valentino RJ , Foote SL
Published: March 2018

These studies were designed to further test the hypothesis that corticotropin-releasing hormone (CRH) is released from axons innervating the noradrenergic neurons of the locus coeruleus (LC) and serves to activate these neurons during stress responses. Specifically, the effects of exogenous CRH on the electrophysiological activity of LC neurons in unanesthetized rats were characterized. Intracerebroventricular (I.C.V.) injection of CRH (0.3–3.0 micrograms) caused a dose-dependent increase in LC spontaneous discharge rates that became statistically significant 6–9 min after injection and was still evident 30–40 min later. A 1.0 and 3.0 micrograms amount of CRH caused peak increases of 86 +/- 32% and 184 +/- 29% (SEM), respectively. In contrast, neither the lowest dose of CRH (0.3 microgram) nor a high dose of Ala 14CRH (3.0 micrograms), an inactive analog of CRH, altered LC spontaneous activity. The effects of CRH administration on sensory- evoked activity of LC neurons were also determined. As previously reported (Foote et al., 1980; Aston-Jones and Bloom, 1981b), the repeated presentation of auditory tone stimuli resulted in a brief enhancement of LC discharge, which was usually followed by a period of relatively decreased activity. Administration of 1.0 or 3.0 micrograms CRH enhanced basal discharge during sensory testing, but discharge rates during the excitatory component of the sensory response were not altered. Quantitative analyses revealed that these doses of CRH produced a statistically significant decrease in the ratio of sensory- evoked to basal discharge rates. Additional analyses of the temporal distribution of discharge activity for individual recording sites during sensory testing demonstrated that 1.0 and 3.0 micrograms CRH altered relative response magnitudes to a statistically significant extent in 7 of 10 and 5 of 7 cases, respectively, while 0.3 microgram CRH and 3.0 micrograms Ala 14CRH were without effect. The present results are consistent with previous studies of CRH effects on LC activity in anesthetized rats (Valentino et al., 1983; Valentino and Foote, 1987). However, in unanesthetized animals, CRH is more potent in increasing tonic activity and does not decrease the absolute magnitude of sensory-evoked activity. The present results support the hypothesis that CRH released from fibers innervating the LC may affect the tonic activity of these cells and the relationship between tonic discharge and phasic, sensory-evoked activity.
Egg-laying hormone, serotonin, and cyclic nucleotide modulation of ionic currents in the identified motoneuron B16 of Aplysia
Authors: Kirk MD , Taussig R , Scheller RH
Published: March 2018

We have used the 2-electrode voltage-clamp technique to analyze the effects of the neuropeptide, egg-laying hormone (ELH), and the biogenic amine 5-HT on ionic currents in the buccal motoneuron B16 of Aplysia. When B16 is voltage-clamped near resting membrane potential, bath- applied ELH induces a prolonged inward shift in holding current. The ELH-induced inward current is not due to a decrease in the transient, the delayed, or the calcium-activated potassium currents. Current- voltage measurements, along with ion substitution and channel-blocking experiments, indicate that ELH primarily induces or increases a voltage- dependent slow inward current carried by sodium. Serotonin also causes a prolonged inward shift in holding current in B16. Like ELH, 5-HT induces or enhances the voltage-dependent inward current carried by sodium. In addition, 5-HT increases an inwardly rectifying potassium current, and, in some preparations, decreases an outward current that is activated when the cell is depolarized to -40 mV and above. None of the currents modulated by ELH or by 5-HT are affected by 200 microM ouabain or by reducing extracellular chloride concentration. Extracellular application of isobutylmethylxanthine (IBMX), forskolin, 8-bromo-cAMP and 8-bromo-cGMP, and intracellular injection of cAMP elicits the slow inward current carried by sodium. The inward current response to ELH is blocked by prior application of 8-bromo-cAMP, while, under these conditions, 5-HT continues to elicit the increase in inward- rectifier potassium current, but decreases the slow inward sodium current. Serotonin also reduces the slow inward sodium current when applied after ELH. These results suggest that the modulation of B16 by ELH may be mediated entirely by either cAMP or cGMP, while at least a portion of the response to 5-HT may involve an unidentified second messenger in addition to cyclic nucleotides.
Development of ganglion cell topography in ferret retina
Authors: Henderson Z , Finlay BL , Wikler KC
Published: March 2018

The adult ferret has approximately 90,000 retinal ganglion cells, arranged in a prominent area centralis and visual streak. The role of differential cell generation, cell death, and retinal growth in the control of adult retinal ganglion cell number and distribution was evaluated by examining basic aspects of retinogenesis, including growth in retinal area, developmental changes in the number, size, and distribution of retinal ganglion cells (identification aided by retrograde transport of HRP), and the incidence of degenerating cells in the ganglion cell layer. Retinal development in the ferret was also compared to retinal development in the cat (which has an even more differentiated area centralis) to determine what alterations of developmental parameters are most closely associated with this species difference in adult morphology. The area of the retina increases linearly from birth (12 mm2) to postnatal day 24 (54 mm2), reaching an eventual adult value of 64 mm2. Ganglion cell numbers peak at 155,000 (approximately twice the adult number) on postnatal day 3, and fall to adult numbers by postnatal day 6. The remaining cells of the ganglion cell layer, principally displaced amacrine cells, reach their peak number on postnatal day 10 (approximately 280,000), falling to 200,000 by adulthood. Degenerating cells are abundant in the ganglion cell layer in the immediate postnatal period. A difference in the incidence of degenerating cells in the presumptive area centralis versus that in the retinal periphery was not observed postnatally, though there were other striking spatial nonuniformities, suggesting that differential cell loss might contribute to other features of retinal topographic organization. Ganglion cell density is virtually uniform across the retina at birth. Cell density is first reduced in the dorsal retina, resulting in a dorsal-to-ventral gradient in cell density that persists until day 10, when ganglion cell number has stabilized. By postnatal day 24, an area centralis and visual streak has emerged, but not of adult magnitude. Because ganglion cell number has stabilized long before the area centralis and visual streak emerge, we conclude that differential retinal growth is the principal mechanism producing this feature of retinal topography. Comparison with the cat suggests that the proportionately greater nonuniform growth of the cat's eye accounts for the greater differentiation of its area centralis.
Reticulospinal vasomotor neurons of the rat rostral ventrolateral medulla: relationship to sympathetic nerve activity and the C1 adrenergic cell group
Authors: Morrison SF , Milner TA , Reis DJ
Published: March 2018

Neurons projecting from the rostral ventrolateral medulla (RVL) to the spinal cord were antidromically identified in rats anesthetized with urethane, paralyzed, and ventilated. The sites of lowest antidromic threshold were concentrated in the intermediolateral nucleus (IML). Their axonal conduction velocities were distributed bimodally, with the mean of the rapidly conducting fibers (greater than 1 m/sec) being 3.1 +/- 0.1 m/sec (n = 105), and of the slower axons being 0.8 +/- 0.03 m/sec (n = 25). Single-shock electrical stimulation of RVL elicited 2 bursts of excitation in splanchnic sympathetic nerve activity (SNA), which resulted from activation of 2 descending pathways with conduction velocities comparable to those of antidromically excited RVL-spinal neurons. The probability of discharge of RVL-spinal cells was synchronized both with the cardiac-related bursts in SNA with functional baroreceptor reflexes and with the free-running 2–6 Hz bursts in SNA following baroreceptor afferent denervation. On the average, their spontaneous discharges occurred 67 +/- 2 msec (n = 31) prior to the peak of the spontaneous bursts in splanchnic SNA. This time corresponded to the latency to the peak of the early excitatory potential in splanchnic SNA following electrical stimulation of RVL. Baroreceptor reflex activation inhibited RVL-spinal neurons. The recording sites of RVL-spinal vasomotor neurons were consistently located within 100 micron of cell bodies (C1 neurons) immunoreactive for the adrenaline-synthesizing enzyme phenylethanolamine N- methyltransferase (PNMT). Ultrastructural analysis of the lateral funiculus of the cervical and thoracic spinal cord demonstrated PNMT immunoreactivity within myelinated (0.6–2.1 micron diameter) and unmyelinated (0.1–0.8 micron diameter) axons. Estimated conduction velocities of these fibers were comparable to the antidromic conduction velocities of the rapidly and slowly conducting populations of RVL- spinal vasomotor neurons. We conclude that in rat, the discharge of RVL- spinal vasomotor neurons strongly influences SNA: the baroreceptor- mediated inhibition of these neurons is reflected in the cardiac locking of SNA, while, in the absence of baroreceptor input, the synchronous discharge of RVL-spinal neurons maintains a free-running 2- 6 Hz bursting pattern in SNA. RVL-spinal neurons are located within, and may be elements of, the C1 adrenergic cell group, and they provide a sympathoexcitatory drive to neurons in the IML over rapidly and slowly conducting pathways that correspond to myelinated and unmyelinated spinal axons containing PNMT.
Synaptic transmission mediated by single club endings on the goldfish Mauthner cell. II. Plasticity of excitatory postsynaptic potentials
Authors: Lin JW , Faber DS
Published: March 2018

Simultaneous pre- and postsynaptic intracellular recordings were used to analyze the properties of chemically mediated synaptic transmission between single club endings of eighth nerve afferents and the goldfish Mauthner (M-) cell lateral dendrite. The EPSPs exhibited pronounced facilitation when the presynaptic fiber fired high-frequency bursts of 2 or 3 impulses at intervals of 2–4 msec. The amplitudes of the EPSPs evoked by the second and third presynaptic impulses of a burst were, on average, 99 and 108% larger than that evoked by the first impulse. A cross-correlation analysis showed that the amplitudes of the control and facilitated EPSPs fluctuated independently, indicating that the facilitation was mediated by a presynaptic mechanism. This conclusion was supported by a comparison of the coefficient of variation for the control and facilitated EPSPs, on the basis of a binomial release model. In addition, the value of binomial n, the number of presynaptic release units, was not changed during facilitation. The origin of EPSP fluctuations was analyzed by examining the correlation between the amplitudes of EPSPs and those of the electrotonic coupling potentials associated with them. The absence of correlation between the 2 variables suggested that the fluctuations of EPSPs were not due to a variable presynaptic impulse invasion. The EPSP fluctuations were further analyzed by assuming that the facilitation was associated with an increase in the probability (p) of transmitter release and that the release process followed simple binomial statistics. The binomial variables thus calculated were n = 6–11, p = 0.29–0.44, and q = 31–61 microV, values comparable to the estimates for other CNS synapses. More importantly, these parameters provided satisfactory fits to the amplitude histograms of the control and facilitated EPSPs. The number of release units, n, was smaller than, but in a range similar to, the number of active zones identified in the freeze-fracture study of the club endings (Kohno and Noguchi, 1986). This correlation is consistent with the notion that active zones are the structural correlates of quantal release units. In the preceding paper, it was shown that impulses in a majority of club endings electrotonically coupled to the M-cell do not produce a detectable chemically mediated EPSP, although the contacts have the morphological correlates of chemical synapses. In an attempt to activate these “silent” connections, 2 approaches were used. First, the burst-firing paradigm, which could effectively facilitate EPSPs already present, failed to reveal any EPSPs at the silent junctions.
The EGPs: the eclosion hormone and cyclic GMP-regulated phosphoproteins. I. Appearance and partial characterization in the CNS of Manduca sexta
Authors: Morton DB , Truman JW
Published: March 2018

The present study describes 2 phosphoproteins, both with an apparent molecular weight of 54 kDa, in the CNS of the tobacco hornworm, Manduca sexta. Their phosphorylation is regulated by a neuropeptide, eclosion hormone (EH), and the second messenger cGMP, which thus have been named the EGPs (eclosion hormone- and cGMP-regulated phosphoproteins). Although cAMP was more effective than cGMP at stimulating the phosphorylation of the EGPs in CNS homogenates, in the intact CNS cGMP was more effective. Since cGMP mediates the action of EH, this strongly suggests that cGMP is the second messenger that stimulates the phosphorylation of the EGPs in vivo. The EGPs can only be phosphorylated in vitro during discrete time periods during the life of Manduca. During the larval and pupal molts, the EGPs can first be phosphorylated just prior to ecdysis. Their ability to be phosphorylated is correlated with the time when the insect is sensitive to EH. This close temporal correlation suggests that the ability to phosphorylate the EGPs determines when the insect can first respond to EH. During adult development, the EGPs first appeared on fluorograms 6 d before sensitivity to EH, suggesting that at this stage other factors may also be involved in the regulation of sensitivity. For the ecdyses of all 3 stages, EH appeared to stimulate the phosphorylation of the EGPs at ecdysis. The EGPs were found in all regions of the prepupal nervous system that were investigated, but only in the abdominal and pterothoracic ganglia of the developing adult. Fractionation of nervous system homogenates by ultracentrifugation revealed that one of the EGPs was present only in the pellet fraction, whereas the other was approximately equally distributed between pellet and supernatant. Furthermore, the EGPs in the pellet fraction could be partially solubilized with detergents and high salt concentrations.
Immunohistochemical localization of benzodiazepine/GABAA receptors in the human hippocampal formation
Authors: Houser CR , Olsen RW , Richards JG , Mohler H
Published: March 2018

Monoclonal antibodies to a purified benzodiazepine/GABAA receptor complex from bovine cerebral cortex were used to determine the localization of this receptor in immunohistochemical preparations of the human hippocampal formation. The regional localization of the receptor was compared with the autoradiographic distribution of binding sites for a benzodiazepine antagonist, Ro 15–1788, and very similar patterns were observed. The highest levels of labeling were present in the molecular layer of the dentate gyrus, where much of the immunoreaction product was localized on the dendrites of granule cells. Lower levels of staining were observed in the granule cell layer, where reaction product was distributed around the perimeter of granule cell somata. The staining patterns varied among the different fields of the hippocampus. Labeling was lowest in the CA3 field, increased somewhat in the CA2 field, and was highest in the CA1 field. Within CA1, a laminar pattern was observed. Moderate to high levels of staining were present in strata oriens, pyramidale, radiatum, and moleculare, whereas less staining was observed in stratum lacunosum. The cellular localization of the receptor also differed among the hippocampal fields. Very little reaction product was observed on pyramidal neurons in the CA3 field, but labeling of pyramidal neurons appeared to increase progressively throughout CA2, CA1, and the subiculum. Nonpyramidal neurons were prominently labeled in all hippocampal fields. These results indicate that the benzodiazepine/GABAA receptor is heterogeneously distributed among the different fields and on different neuronal cell types of the human hippocampus.
A desensitized form of neuronal acetylcholine receptor detected by 3H- nicotine binding on bovine adrenal chromaffin cells [published erratum appears in J Neurosci 1988 Dec;8(12):preceding 4415]
Authors: Higgins LS , Berg DK
Published: March 2018

A nicotinic acetylcholine receptor (AChR) on bovine adrenal chromaffin cells in culture has previously been identified using the alpha- neurotoxin n-Bgt and the monoclonal antibody mAb 35. Here, we report that the cells have 2 classes of high-affinity binding sites for 3H- nicotine, one being associated with the AChR and the other being associated with the alpha-bungarotoxin binding component that is distinct from the AChR. Scatchard analysis of 3H-nicotine binding to the AChR site yields a KD of 20 +/- 3 nM and a Bmax of 104 +/- 12 fmol/mg protein. Nicotinic antagonists block 3H-nicotine binding to the AChR site with the same rank order of potency and affinity with which they block nicotine-induced catecholamine release from the cells. About 80% of the AChRs are on the cell surface, as judged by the distribution of both 3H-nicotine binding and 125I-mAb 35 binding to the receptor, and the ratio of nicotine/mAb 35 binding to the AChR on the cell surface is approximately 1:1. Chronic treatment of the cells with mAb 35 results in receptor modulation such that all of AChR-related nicotine binding is lost from the cell surface, and all of the functional response to nicotine is lost as well. The results confirm that 3H-nicotine binding is associated with AChRs on the cells. The 3H- nicotine binding observed to the AChR represents binding to a desensitized form of the receptor having increased affinity for agonists and unchanged affinity for antagonists. This conclusion derives from the following observations. The KiS for agonist competition of 3H-nicotine binding indicate agonist affinities several orders of magnitude greater than do the KDS measured for receptor activation. Exposing cultures to low concentrations of nicotine and substance P causes receptor densensitization, and the concentration dependence of the nicotine-induced desensitization displays an EC50 of 20 nM, in good agreement with the KD obtained from equilibrium binding studies with 3H-nicotine. In addition, the rate of 3H-nicotine binding is increased both by substance P, which enhances the rate of agonist- induced desensitization on adrenal chromaffin cells, and by preincubation with nicotine. The increased rate of association, together with the dissociation rate, yields a kinetically derived KD of 19 nM, again in good agreement with the KD obtained from equilibrium binding studies. These results demonstrate that the bovine adrenal chromaffin AChR is similar to AChRs from muscle and electric organ in undergoing an agonist-induced conversion to a desensitized state having increased affinity for agonists.
Mouse cerebellar granule neurons arrest the proliferation of human and rodent astrocytoma cells in vitro
Authors: Hatten ME , Shelanski ML
Published: March 2018

To understand the control of glial tumor cell proliferation, we have examined the effects of neurons on a number of human and rodent glioma lines. These included C6, G26–24, U-251, HTB-16, and A-172 cells of astroglial lineage and G26–20 of bipotential astrocytic and oligodendrocytic lineage. Rapid, specific binding of granule neurons to the human A-172, HTB-16, and U-251 and mouse G26–24 cell lines occurred, after which 3H-thymidine incorporation by these astrocytoma cells dropped 2–5-fold within 12 hr. The number of glial cells remained constant for 5–7 d when the glia were cocultured with granule neurons. Thereafter many neurons detached from the glial cells and glial proliferation commenced again. No effects on glial cell number were seen when PC12 cells were substituted for cerebellar granule neurons. To test the mechanism of neuronal control of glioma cell growth, we added granule neurons or PC12 cells that had been fixed lightly with paraformaldehyde, a plasma membrane fraction of purified granule cells, PC12 cells or astrocytoma cells, or medium conditioned by either granule cells or a mixed population of cerebellar neurons and astroglia. The proliferation of responsive glioma cell lines ceased in the presence of either fixed granule neurons or plasma membranes purified from granule neurons. The addition of fixed PC12 cells or plasma membranes purified from PC12 cells, 3T3 cells, or astrocytoma cells had no effect on glial cell growth.
Functional anatomy of macaque striate cortex. IV. Contrast and magno- parvo streams
Authors: Tootell RB , Hamilton SL , Switkes E
Published: March 2018

Macaque monkeys were shown achromatic gratings of various contrasts during 14C-2-deoxy-d-glucose (DG) infusion in order to measure the contrast sensitivity of different subdivisions of primary visual cortex. DG uptake is essentially saturated at stimulus contrasts of 50% and above, although the saturation contrast varies with layer and with different criteria. Following visual stimulation with gratings of 8% contrast, stimulus-driven uptake was relatively high in striate layer 4Ca (which receives primary input from the magnocellular LGN layers), but was absent in layer 4Cb (which receives primary input from the parvocellular layers). In this same (magnocellular-specific) stimulation condition, striate layers 4B, 4Ca, and 6 showed strong stimulus-induced DG uptake, and layers 2, 3, 4A, and 5 showed only light or negligible uptake. By comparison to other cases that were shown stimuli of systematically higher contrast, and to a wide variety of DG cases shown very different stimuli, it is evident that information derived from the magnocellular and parvocellular layers in the LGN remains partially, or largely, segregated in its passage through striate cortex, and projects in a still somewhat segregated fashion to different extrastriate areas. The sum of all available evidence suggests that the magnocellular information projects strongly through striate layers 4Ca, 4B, and 6, with moderate input into the blobs in layers 2 + 3, and to blob-aligned portions of layer 4A. Parvocellular-dominated regions of striate cortex include both the blob and interblob portions of layers 2 + 3, 4A, 4Cb, and 5. Because the major striate input to V2 arrives from striate layers 2 + 3, and because the major striate input to MT originates in layer 4B and 6, it appears that area V2 receives information derived largely from the parvocellular LGN layers, and that area MT receives information derived mainly from the magnocellular layers.
Electrotonic synapses between Aplysia neurons in situ and in culture: aspects of regulation and measurements of permeability
Authors: Bodmer R , Verselis V , Levitan IB , Spray DC
Published: March 2018

Properties of electrotonic synapses between L14 neurons in the abdominal ganglion of the marine mollusc Aplysia californica were examined in situ and between unidentified buccal neurons maintained in tissue culture. In culture, depolarizing postsynaptic potentials in response to a train of action potentials showed apparent facilitation with increasing spike number, which was attributable to the low-pass filter properties of electrotonic transmission via gap junctions and to network properties. Gap junctional conductance (gj), calculated from current-clamp data or measured directly under voltage clamp, indicated no significant dependence of gj on transjunctional or inside-outside potential in situ or in culture. Octanol, a local anesthetic agent that reduces gj in many other systems, had no effect on gj between Aplysia neurons. The effect of intracellular acidification, a treatment that rapidly and reversibly uncouples a variety of cell types, reduced gj between Aplysia neurons but did not completely abolish it. The relationship between intracellular pH (pHi), measured with ion- sensitive microelectrodes, and gj was steeper in cultured neurons than in situ and was maximally reduced by 70–80%, as compared to 50% or less in situ at the lowest pHi values tested. The coupling coefficient (k) was reduced less by low pHi than was gj, which could be explained by a simultaneous increase in nonjunctional membrane resistance. Permeability properties of Aplysia electrotonic synapses to a variety of tracer molecules were also examined between identified L 14 neurons in situ and in dissociated buccal, abdominal, and bag neurons in culture. The fluorescent dyes Lucifer yellow, 6-carboxyfluorescein, and dichlorofluorescein (1.2–1.4 nm maximal diameters) did not spread detectably from an injected neuron to its electrically coupled neighbors, regardless of the strength of electrotonic coupling. However, the smaller tetraalkylammonium ions TMA and TEA (diameters 0.66 and 0.8 nm, concentrations measured with ion-selective electrodes), could be detected in neighboring cells within minutes. In culture, transfer of the tetraalkylammonium ions was slow and not easily detectable in cell pairs where gj was low (less than 20 nS). The permeability was as high as 10(-10) cm3/sec in situ and 10(-12) cm3/sec in culture, and values were roughly correlated with simultaneously measured values of gj. Electrotonic synapses in the nervous system of Aplysia, therefore, have a quantitatively different spectrum of sensitivities than has been found for gap junctions of other systems and appear to possess reduced permeability to tracer molecules.
Contributions of cingulate cortex to two forms of spatial learning and memory
Authors: Sutherland RJ , Whishaw IQ , Kolb B
Published: March 2018

The contribution of anterior and posterior cingulate cortical areas to spatial learning and memory was examined in 4 experiments using the place-navigation task. Rats with complete bilateral cingulate cortex aspiration or aspiration of posterior cingulate cortex (area 29) alone could not swim directly to a hidden platform located in a fixed place. When animals with these lesions were tested for 40 d in a place- alternation task in which they received 16 daily trials with the platform placed in a new location each day, they did not show reliable improvement in place navigation. The inability to swim to changing locations or to a single location was not overcome by preoperative training in these tasks. Rats with anterior cingulate cortex aspirations showed a less severe impairment in both tasks and, with more training than is necessary for control rats, they acquired near- normal place-navigation accuracy. Rats with complete cingulate cortex aspiration were almost as accurate as control rats in learning to swim to a visible platform. The results imply that posterior cingulate areas play an essential role in the use of topographical information, probably by transmitting and elaborating information passing between the hippocampal system and neocortical association areas.
Infrapyramidal mossy fibers and two-way avoidance learning: developmental modification of hippocampal circuitry and adult behavior of rats and mice
Authors: Lipp HP , Schwegler H , Heimrich B , Driscoll P
Published: March 2018

The extent of the intra- and infrapyramidal mossy fiber projection (IIP- MF) in the hippocampus of mice and rats is strain-specific, and correlates negatively with the strain-specific capacity of avoidance learning. If variations of the IIP-MF influence the capacity for 2-way avoidance learning, then developmental modification of the IIP-MF projection in an individual member of a strain should remain correlated with its adult behavior. Pups of strains with high avoidance capacity and small IIP-MF projections (RHA rats, DBA/2 and BALB/c mice) were injected with varying doses of thyroxine during the postnatal period. This transient hyperthyroidism resulted in a strong, yet largely unpredictable, variability of the IIP-MF projection in the adult animals. Furthermore, postnatal saline injections also increased the variability of the IIP-MF projection; however, this was to a lesser degree than when using thyroxine. The animals were tested for 2-way avoidance learning at the age of 90–120 d. Many showed strain-atypical avoidance scores. These deviations from the inherited level of 2-way avoidance learning were strongly correlated with the magnitude of the IIP-MF projection, regardless of whether the structural changes resulted from thyroxine or saline injections. A multivariate analysis showed that the observed correlations could neither be explained by thyroxine-induced changes in brain weight nor by individual differences of other terminal fields in the hippocampal region CA3. These results suggest that the extent of the IIP-MF projection is influenced by several genetic and epigenetic factors. Irrespective of the underlying causes, the magnitude of the IIP-MF (or of an unknown but well- correlated variable) appears to bias the adult capacity for 2-way avoidance learning predictably.
K+ at concentrations reached in the extracellular space during neuronal activity promotes a Ca2+-dependent glycogen hydrolysis in mouse cerebral cortex
Authors: Hof PR , Pascale E , Magistretti PJ
Published: March 2018

The effect of increasing [K+]0 on 3H-glycogen levels was examined in mouse cerebral cortical slices. K+ stimulates in a time- and concentration-dependent manner the hydrolysis of 3H-glycogen. Over 70% of the maximal effect is reached within 30 sec and the EC50 for the glycogenolytic action of K+ is 11 mM. Significant 3H-glycogen hydrolysis occurs at 5–12 mM [K+]0, concentrations reached by the ion in the extracellular space during neuronal activity. The K+-evoked glycogenolysis is Ca2+-dependent, and is inhibited by Ca2+-channel blockers such as Ni2+ and Mn2+, but not by Cd2+, nifedipine, and omega- conotoxin. Furthermore, the effect of K+ is not enhanced by the Ca2+- channel agonist Bay K 8644. This type of pharmacological profile suggests that the activation of voltage-sensitive Ca2+ channels of the T subtype mediates the glycogenolytic action of K+. This set of observations suggests that K+ released in the extracellular space by active neurons may promote the mobilization of energy substrates and therefore play a role in the coupling between neuronal activity and energy metabolism.
Quantitative autoradiographic localization of prostaglandin E2 binding sites in monkey diencephalon
Authors: Watanabe Y , Watanabe Y , Hayaishi O
Published: March 2018

Quantitative autoradiography was performed to investigate the mapping of prostaglandin E2 binding sites in the Macaca fuscata fuscata diencephalon. Autoradiographs were prepared by incubation of 10-micron- thick serial frozen sections with 3H-prostaglandin E2 and were processed by using a rotating drum-scanner and a computer-assisted image-processing system with 3H-microscales as standards. The localization of prostaglandin E2 binding sites was remarkably discrete in the diencephalon. The highest concentrations were found in the median and medial preoptic areas, supramammilary nucleus of the hypothalamus, and centromedian nucleus of the thalamus. High density was observed in the medial and dorsal hypothalamic areas; paraventricular, anterior, dorsomedial, and infundibular nuclei of the hypothalamus; and in the anteroventral, periventricular, paraventricular, laterodorsal, and habenular nuclei of the thalamus. The distribution correlates well with the known effects of prostaglandin E2 and may also give us useful clues in unveiling the novel role of prostaglandin E2 in a variety of brain functions.
Identification and characterization of neurons initiating patterned neural activity in the buccal ganglia of Aplysia
Authors: Susswein AJ , Byrne JH
Published: March 2018

Two patterns of neural activity were identified in excised buccal ganglia of Aplysia californica. Both are expressed in many cells, and each can be expressed independently. Using cells B4 and B5 as monitors of the activity patterns, we searched the buccal ganglia for cells initiating the patterns. Two electrically coupled cells, B31 and B32, can initiate what we termed pattern 2. The cells are active before pattern 2 is expressed. Stimuli initiating pattern 2 excite B31/B32. Depolarizing B31/B32 induces the pattern, while hyperpolarizing them can prevent its expression. The cells have unusual features. Their somata do not sustain conventional action potentials, and depolarization causes a regenerative response. B33 differs from B31/B32 in that its soma sustains conventional action potentials but otherwise has similar features. B34 also seems to be inexcitable but has weaker synaptic input than B31/B32 and appears unable to induce pattern 2. B35 and B36 have prominent regenerative capabilities. B35 is also able to initiate pattern 2. B37 is presynaptic to B31/B32 and can initiate pattern 2 via its effects on them. The newly identified cells provide a starting point for investigating factors that initiate and control different patterns of neural activity in the buccal ganglia. Since the buccal ganglia are involved in generating feeding behavior, further studies on the newly identified cells may provide insights into the neural control of feeding behavior, and provide a neural substrate for studying modulation of the feeding patterns by associative learning.
Comparison of primary afferent and glutamate excitation of neurons in the mammalian spinal dorsal horn
Authors: Schneider SP , Perl ER
Published: March 2018

The actions of L-glutamate and agonists, agents blocking their membrane receptors and dorsal root afferent volleys, were compared on intracellularly recorded neuronal activity in an in vitro horizontal slice preparation of the hamster spinal dorsal horn. Bath-applied L- glutamate or L-aspartate (less than or equal to 1 mM) rapidly depolarized and excited less than a third of the dorsal horn neurons sampled. Bathing solutions containing low Ca2+ eliminated synaptic transmission in the slices but failed to block the excitatory effects of L-glutamate for the majority of the neurons tested. N- Acetylaspartylglutamate had no effect on dorsal horn neurons at concentrations up to 1 mM. Neurons excited by L-glutamate were most commonly located in the superficial dorsal horn (laminae I and II). Neurons insensitive to L-glutamate were more broadly distributed, with a number being located in laminae III-V. Kynurenic acid, 2-amino-4- phosphonobutyric acid, and 2,3-piperidine dicarboxylic acid selectively antagonized rapid, short-lasting synaptic components of the dorsal cord potentials. Kynurenic acid reversibly antagonized intracellularly recorded L-glutamate-induced excitation, spontaneous synaptic potentials, and fast synaptic potentials evoked by dorsal root volleys. Compounds with strong antagonist actions at the NMDA receptor, 2-amino- 5-phosphonovaleric acid and D-alpha-aminoadipic acid, were much less effective in suppressing the effects of L-glutamate or in blocking synaptic potentials. We conclude that a subset of spinal neurons directly excited by dorsal root fibers have excitatory membrane receptors activated by L-glutamate. This conclusion is consistent with the concept that L-glutamate or a substance binding to the receptors it activates is released from the central terminals of some primary afferent fibers and mediates fast synaptic transmission from them to certain spinal neurons in the dorsal horn.
Outgrowth-regulating actions of glutamate in isolated hippocampal pyramidal neurons
Authors: Mattson MP , Dou P , Kater SB
Published: March 2018

The present study examined the effects of glutamate on the outgrowth of dendrites and axons in isolated hippocampal pyramidal-like neurons in cell culture. During the first day of culture the survival and outgrowth of these neurons was unaffected by high concentrations (up to 1 nM) of glutamate, quisqualic acid (QA), kainic acid (KA), and N- methyl-D-aspartic acid. Beginning on day 2 of culture high levels of glutamate, KA and QA were toxic to the majority of pyramidal neurons, while subtoxic levels of these agents caused a well-defined, dose- dependent, sequence of effects on dendritic outgrowth. At increasing concentrations of glutamate, QA, and KA, the following events were observed: (1) dendritic outgrowth rates were reduced, while axonal elongation rates were unaffected; (2) dendritic length was reduced, while axons continued to grow; (3) dendrites regressed dramatically, and axonal outgrowth rate was reduced. These dendrite-specific effects of glutamate were apparently mediated at the growth cones since focal application of glutamate to individual dendritic growth cones resulted in suppression of growth cone activity and a regression of the dendrite; axons were unaffected by focal glutamate application. Pharmacological tests using glutamate receptor agonists and antagonists demonstrated that receptors of the KA/QA type mediated the glutamate effects on outgrowth and survival. The calcium channel blocker Co2+ prevented both glutamate neurotoxicity and glutamate-induced dendritic regression. Ionophore A23187 and elevations in extracellular K+ levels each caused a dose-dependent series of outgrowth and survival responses similar to those caused by glutamate. Taken together, these results indicate that activation of glutamate receptors leads to the opening of voltage-dependent calcium channels; the resulting increases in calcium influx lead to the observed alterations in dendritic outgrowth and neuronal survival.
Voltage-gated potassium currents in cultured ovine oligodendrocytes
Authors: Soliven B , Szuchet S , Arnason BG , Nelson DJ
Published: March 2018

Cultured oligodendrocytes (OLGs) develop processes and form myelin following attachment to a substratum. We applied the whole-cell voltage- clamp technique to identify and characterize the ionic currents of OLGs in culture. Within 2 d after attachment, OLGs extended processes and began to express an outward current that represents a composite response of an inactivating/transient component and a non-inactivating component. The current had a reversal potential of -66 mV and was sensitive to potassium channel blockers. After 4–5 d in culture, the transient component was less prominent, often accompanied by an increase in noninactivating or steady-state outward current. In addition, there was an increase in inward rectifier current. Four of 7 cells that failed to develop processes exhibited only linear high- resistance membranes. We conclude that cultured OLGs express 3 voltage- gated potassium conductances: (1) a transient outward current, (2) a noninactivating outward current, and (3) an inward rectifier current. The sequential appearance of the several currents may relate, at least in part, to process formation.
Spatial distribution of motor unit fibers in the cat soleus and tibialis anterior muscles: local interactions
Authors: Bodine SC , Garfinkel A , Roy RR , Edgerton VR
Published: March 2018

The spatial distribution of muscle fibers belonging to a motor unit was studied in the soleus and tibialis anterior muscles of adult cats. Motor unit fibers were depleted of their glycogen through repetitive stimulation of the motoneuron or of the functionally isolated motor axon. Subsequently, the position of depleted muscle fibers was mapped on serial cross sections taken along the length of the muscle. A subset of fibers was selected from the cross section containing the largest number of motor unit fibers and 4 spatial analyses were performed. These analyses were designed to determine whether the muscle fibers belonging to a single unit were distributed in a random manner. To test whether the actual distribution was other than random, Monte Carlo techniques were used to simulate the random innervation of a muscle. From these simulations, a test statistic was calculated for comparison with the observed data. Adjacency and nearest-neighbor analyses revealed no tendency for grouping or dispersion of fibers belonging to a motor unit. However, measurement of the distances between all motor unit fibers revealed a greater tendency for grouping than spreading, suggesting the existence of some mechanism that restricts the absolute distribution and territory of a motor unit.