bluuebunny/crossref_metadata_2025 huggingface dataset:
Functional anatomical studies of explicit and implicit memory retrieval tasks
Authors: Buckner RL , Petersen SE , Ojemann JG , Miezin FM , Squire LR , Raichle ME
Published: April 2018

Across three experiments, PET scans were obtained while subjects performed different word-stem completion and FIXATION control tasks designed to study the functional anatomy of memory retrieval. During each of three different word-stem completion scans, word-stem cues were visually presented in uppercase letters. The RECALL task required explicit retrieval of study words presented prior to the PET scan. The PRIMING task addressed the implicit effects of the prior study words without requiring intentional recall. The BASELINE task encouraged retrieval of information from a general knowledge store. Across experiments, the similarity between study words and word stems was manipulated by presenting prescan study words in either uppercase letters identical to the stems, in lowercase letters, or auditorily. The PRIMING task was not studied with auditory presentation. Many activations were consistent across experiments. The BASELINE task activated several regions in response to the reading and verbal- response demands of the task (visual, motor, and premotor cortices, cerebellum), as well as a left prefrontal region. The RECALL task additionally activated regions in anterior right prefrontal cortex. Bilateral occipitotemporal regions showed blood flow reductions during the PRIMING task as compared to the BASELINE task. Activation in the right hippocampal/parahippocampal region was observed only in one experiment, and no experiment showed activation in the left medial temporal lobe. These experiments suggest that areas of frontal cortex play a role in explicit recall and that an effect of priming may be to require less activation of perceptual regions for the processing of recently presented information.
Facilitatory coupling between a glutamate metabotropic receptor and dihydropyridine-sensitive calcium channels in cultured cerebellar granule cells
Authors: Chavis P , Nooney JM , Bockaert J , Fagni L , Feltz A , Bossu JL
Published: April 2018

The effect of metabotropic glutamate receptor activation on Ca dihydropyridine (DHP)-sensitive channels recorded in the presence of 1 microM Bay K 8644 was examined on cultured cerebellar granule cells using the patch-clamp technique in the cell-attached configuration. Bath-applied agonist (trans-ACPD, 1S,3R-, and 1R,3S-ACPD isomers, and glutamate or quisqualate in the presence of CPP and CNQX) evoked an increase in Ca channel activity with a variable latency of 8.9 +/- 8.6 sec in 40% of the recorded cells. Neither L-CCG1, L-AP3, L-AP4, nor AMPA or NMDA activated Ca channels. Two dihydropyridine-sensitive channels present in this cell type were activated by trans-ACPD: the classical 24 pS L-type channel and a smaller-conductance 7 pS channel. The effect was shown to be mediated by neither intracellular Ca2+ nor a pertussis toxin (PTX)-sensitive G protein. Interestingly treatment with BAPTA-AM increased the number of responding patches and the activity was more sustained throughout the drug application. After overnight PTX treatment, activation of the Ca channels persisted even after washout of the agonist. These results indicate that mGluR1/mGluR5 probably mediate the facilitation of dihydropyridine-sensitive Ca channels.
Beta 2-adrenergic receptors are expressed by glia in vivo in the normal and injured central nervous system in the rat, rabbit, and human
Authors: Mantyh PW , Rogers SD , Allen CJ , Catton MD , Ghilardi JR , Levin LA , Maggio JE , Vigna SR
Published: April 2018

Previous studies have demonstrated that glial cells in culture express several subtypes of functional adrenergic receptors. To determine if similar receptors are expressed by glia in vivo, we examined the expression of adrenergic receptors in the normal, crushed, and transected optic nerves of the rabbit and rat using quantitative receptor autoradiography. Additionally, we examined the expression of adrenergic receptors in the normal and damaged human optic nerve. High levels of alpha 1-, alpha 2-, beta 1-, and beta 2-adrenergic receptors were identified in the rabbit and rat forebrain. In the normal rabbit, rat, and human optic nerves, only alpha 1 and beta 2 receptors were observed, and these were present in low to moderate densities. Combined immunohistochemistry and autoradiography suggests that the majority of beta 2-adrenergic receptors in the rabbit, rat, and human optic nerve are expressed by astrocytes. After unilateral optic nerve crush or transection, only beta 2- adrenergic receptors were significantly increased. This increase in beta 2 receptors was first detectable at days 7 and 28 post-transection in the rabbit and rat, respectively. The expression of beta 2 receptors in the transected optic nerve continued to increase with time, so that by 90 d post-transection the density of beta 2 receptors in both the rabbit and rat optic nerve was among the highest of any area in the forebrain. Taken together with previous studies, these results suggest that in vivo, beta 2-adrenergic receptors may provide a therapeutic target for regulation of astrocyte functions including glycogen metabolism, cytokine release, and the hypertrophy and proliferation that occurs in response to neuronal injury.
Perineurial defect and peripheral opioid analgesia in inflammation
Authors: Antonijevic I , Mousa SA , Schafer M , Stein C
Published: April 2018

Opioid receptors have been demonstrated on sensory nerves in both inflamed and normal subcutaneous tissue but locally applied opioid agonists produce analgesia in inflamed tissue only. Inflammation confers a disruption of the perineurial barrier that can also be induced deliberately by hyperosmolar solutions. The present study examines at which stage of Freund's adjuvant-induced inflammation peripheral opioid analgesic effects become manifest and whether a perineurial defect contributes to the appearance of such effects. To this end we have monitored the temporal evolution of inflammatory signs (swelling, temperature, hyperalgesia) and of peripheral antinociceptive effects (by the paw pressure test) of mu-, delta-, and kappa-selective opioids. Using horseradish peroxidase histochemistry, the perineurial barrier was assessed in normal and inflamed tissue and following its artificial disruption by hyperosmolar saline and mannitol in vivo. Finally, we sought to elicit analgesia in normal tissue by the concomitant application of mannitol and receptor-selective opioids or by an extremely lipophilic opioid agonist (fentanyl). We found that peripheral opioid antinociception and perineurial leakage occur simultaneously at a very early stage (within 12 hr) of the inflammatory reaction and that both can be mimicked by the administration of hyperosmolar solutions in normal tissue. Fentanyl produced peripheral antinociception in noninflamed tissue that was potentiated by mannitol or inflammation. Our findings demonstrate that the perineurium is a crucial determinant for peripheral opioid analgesia and that the efficacy of locally applied hydrophilic or lipophilic neuromodulatory compounds can be improved dramatically by the concomitant modulation of perineurial permeability.(ABSTRACT TRUNCATED AT 250 WORDS)
Influences of vestibular and visual motion information on the spatial firing patterns of hippocampal place cells
Authors: Sharp PE , Blair HT , Etkin D , Tzanetos DB
Published: April 2018

Hippocampal place cells show location-specific firing as animals locomote in an environment. A possible explanation for these place fields is that each cell is simply driven by environmental sensory inputs available in its field. This cannot provide the full explanation, however, since cells can maintain stable place fields even in the absence of reliable environmental orienting cues. This suggests the cells are also influenced by movement-related information, since this is the only available, ongoing indicator of current location when external orienting cues are not present. Two candidates for the movement-related information are vestibular activation, and visual motion. To test for these influences, place cells were recorded as animals locomoted in a cylindrical apparatus that was made so that its wall (painted with vertical black and white stripes) and floor could be independently rotated, to provide visual motion and vestibular inputs, respectively. The results showed that both these inputs could influence place fields. Sometimes they caused a predictable locational shift, so that the field rotated its location on the apparatus floor in a way that was compatible with the movement indicated by the vestibular and/or visual motion input. This updating was most reliably obtained when the two inputs were presented in combination. In other cases, the apparatus rotations caused unpredictable changes in firing characteristics, so that cells either stopped firing, or developed place fields that were altered in overall size, shape, and eccentricity. Interestingly, the probability of these changes increased with experience with the rotational manipulations, suggesting a learned component.
Specialized neuronal and glial contributions to development of the hamster lateral geniculate complex and circadian visual system
Authors: Botchkina GI , Morin LP
Published: April 2018

The intergeniculate leaflet (IGL) is an integral part of the adult circadian visual system. It is characterized by the presence of retinal afferents and peptidergic cells projecting via a geniculohypothalamic tract (GHT) to the suprachiasmatic nucleus (SCN), site of the mammalian circadian clock. The adult IGL also contains abundant reactive astrocytes immunoreactive to GFAP. Because glia have a large role in brain development, we examined the ontogeny of the hamster IGL with respect to both glial and neuronal markers. Neuropeptide Y- immunoreactive (NPY-IR) cells destined for the IGL appear on embryonic day 11 (E11) in a matrix of vimentin (VIM)-IR radial glia. Migratory ellipsoid NPY-IR cells with long leading and trailing processes become oriented between the reticular thalamic neuroepithelial lobule, and the developing IGL. Most NPY-IR cells arrive in the IGL by E14 and extend axons ventrally into the GHT. These penetrate the SCN at P3 and arborize to an adult-like stage by P10. A specialized GFAP-IR radial glial path coinciding with the migratory route of NPY-IR cells appears by E14. As early as E15, cells contributing to this path are found displaced away from the ventricle. As the glial path disappears from the maturing brain, the entire length of the IGL becomes filled with GFAP-IR astrocytes. These features are consistent with translocation and transformation of a specialized set of radial glia into IGL astrocytes. The results demonstrate that the IGL is a large, developmentally important, feature of the lateral geniculate complex that is embryologically distinct from adjacent dorsal and ventrolateral geniculate nuclei.
Differential regulation of neuronal sodium channel expression by endogenous and exogenous tyrosine kinase receptors expressed in rat pheochromocytoma cells
Authors: Fanger GR , Jones JR , Maue RA
Published: April 2018

The biological activity of growth factors that act through receptor tyrosine kinases (RTKs) can differ dramatically, depending on both the properties of the RTKs and the cellular environment in which the RTKs are expressed. To determine the ability of different RTKs to elicit ras- independent responses central to neuronal differentiation, we analyzed voltage-dependent sodium (Na) channel expression in rat pheochromocytoma (PC12) cells after activation of a variety of endogenously and exogenously expressed RTKs. In PC12 cells expressing trkB (Ip et al., 1993), the increase in Na current density caused by brain-derived neurotrophic factor (BDNF) was similar to that observed upon activation of endogenous trkA by NGF. BDNF also increased type II Na channel mRNA expression, as did neurotrophin-3 in PC12 cells expressing trkC (Tsoulfas et al., 1993). In contrast, insulin did not increase type II Na channel mRNA expression or Na current density in PC12 cells, while epidermal growth factor (EGF) elicited small, yet reproducible increases in type II Na channel mRNA and Na current density when compared to NGF, even upon coexpression of an EGF receptor/p75 receptor chimera (Yan et al., 1991). Finally, in PC12 cells expressing beta-platelet-derived growth factor (PDGF) receptors (Heasley and Johnson, 1992), PDGF increased type II Na channel mRNA and Na current density to the same extent as NGF. The results show the capabilities of these RTKs in eliciting Na channel expression and the specificity arising due to differences in their intrinsic properties.
Antagonist and partial agonist actions of d-tubocurarine at mammalian muscle acetylcholine receptors
Authors: Steinbach JH , Chen Q
Published: April 2018

Currents were elicited by acetylcholine (ACh), by d-tubocurarine (dTC), and by mixtures of ACh and dTC, from stably transformed fibroblasts that express fetal or adult muscle nicotinic receptors. dTC acted as an antagonist of ACh for activation of adult-type receptors, whereas it acted as a weak partial agonist at fetal-type receptors. The channel- blocking action of dTC was not apparent at the concentrations used. The partial agonism could explain previous observations that dTC is less effective at blocking the responses of fetal-type receptors than adult- type receptors. Binding of dTC to receptors was independently assayed by measuring the reduction of the initial rate of binding of iodinated alpha-bungarotoxin. Binding of dTC to the two types of receptor was indistinguishable. The dose-effect relationship for the interaction of dTC and ACh at fetal receptors is consistent with the affinities of dTC measured in binding experiments.
Transforming growth factor-beta 1 and forskolin modulate gap junctional communication and cellular phenotype of cultured Schwann cells
Authors: Chandross KJ , Chanson M , Spray DC , Kessler JA
Published: April 2018

Following peripheral nerve injury, Schwann cells undergo a series of cellular alterations that are thought to assist the regenerative process. Some of these changes are stimulated by the local release of cytokines and mitogenic factors. To test the hypothesis that cytokine regulation of gap junctional communication between cells helps to coordinate Schwann cell responses, cultured rat Schwann cells, from sciatic nerve, were utilized to study phasic changes induced by transforming growth factor-beta 1 (TGF beta 1), a cytokine released after nerve injury, or forskolin in combination with bovine pituitary extract (F-BPE), known for its mitogenic effects in vitro. In mitotically quiescent cultures, TGF beta 1 significantly decreased both electrical and dye coupling mediated by gap junctions. Single-channel analysis revealed that cultured Schwann cells expressed gap junctions with two distinct channel sizes of about 26 pS and 44 pS. TGF beta 1 treatment reduced coupling due to both populations of channels. Exposure to TGF beta 1 had a minimal effect on proliferation but significantly altered cellular morphology; cell bodies became flattened with multipolar processes within 72 hr. Additionally, immunolabeling for both low-affinity nerve growth factor receptor (L-NGFR) and glial fibrillary acidic protein (GFAP) were reduced, suggesting increased differentiation. In contrast, treatment with F-BPE significantly enhanced both electrical and dye coupling and stimulated Schwann cell proliferation. Additionally, cell bodies became more rounded with polarized, cytoplasmic processes contiguously aligned with adjacent cells. F-BPE reduced immunolabeling for L-NGFR but increased expression of both GFAP and the major peripheral myelin protein, P0. These data indicate that TGF beta 1 and/or F-BPE induce phenotypic changes in Schwann cells, including the coordinated regulation of proliferation and modulation of intercellular communication via gap junctions. Such mechanisms may underlie phasic responses that orchestrate recovery from nerve injury, indicating that Schwann cell gap junctions may be critical for peripheral nerve function.
Characterization of voltage-activated currents in Hermissenda type B- photoreceptors
Authors: Acosta-Urquidi J , Crow T
Published: April 2018

Two distinct voltage-dependent K+ currents have been previously identified in the type B-photoreceptors of Hermissenda: an early, rapidly inactivating K+ current (IA), and a late, 4-AP- and TEA- resistant voltage and Ca(2+)-dependent current (IK(Ca)). Using conventional two-electrode voltage-clamp techniques, we have characterized two additional currents, a late voltage-dependent outward K+ current (IK(v)) and a voltage-dependent inward current identified as an inward rectifier (Iir). In addition, we have further studied the activation-inactivation kinetics of IA. In 0-Na+ ASW, Iir activates at a potential of > -50 mV, is steeply voltage-dependent and noninactivating, and reaches steady-state within 800 msec to 3 sec at - 100 mV. In addition to the variability in activation kinetics, there was also considerable variability in Iir magnitude (-5 to -80 nA, at - 100 mV). Iir was blocked by external 4-AP (5 mM), external and internal TEA, internal Cs+, but not external Ba2+. The major component of outward K+ current in type B-photoreceptors is IK(v), the delayed rectifier. IK(v) was isolated after removal of IA and IK(Ca). IK(v) activates at around -25 mV or more positive membrane potentials and its activation and inactivation are strongly voltage dependent. IK(v) inactivation to steady state is reached within 1.5–2.5 sec. The wide range of activation-inactivation rates suggests that there may be kinetic subtypes of IK(v). The proposed “slow” IK(v) peaked in 50–90 msec at +30 mV, and decayed with a single exponential component with an average tau off of 279 msec. Proposed “intermediate” and “fast” IK(v) subtypes peaked within 12–50 msec at +30 mV, and had a decay fitted by two exponentials, with an average tau 1 of 147 msec and tau 2 of 275 msec, respectively. IK(v) exhibited marked twin-pulse inactivation with a recovery time of 30–40 sec, and also exhibited time- and voltage- dependent cumulative inactivation to repeated depolarizing pulses. Both types of inactivation were quickly removed by a prepulse hyperpolarization. 4-AP (5 mM) produced partial to complete block of the inactivating component of IK(v), leaving only a residual sustained component. Complete block of the transient and sustained components of IK(v) was obtained by 100 mM TEA. Reliable voltage separation of IA from IK(v) was achieved by activating IA in the range of -50 to -20 mV, from a Vh of -80 mV. Voltage-dependent steady-state inactivation curves for IA were determined, yielding an average h0.5 value of -56 mV.(ABSTRACT TRUNCATED AT 250 WORDS)
Neuron-specific enolase: a neuronal survival factor in the retinal extracellular matrix?
Authors: Li A , Lane WS , Johnson LV , Chader GJ , Tombran-Tink J
Published: April 2018

To identify soluble proteins of the retinal interphotoreceptor matrix (IPM), we isolated IPM from the bovine eye by gentle lavage and subjected it to SDS-PAGE. In the resultant gel, a 46 kDa band was particularly prominent and appeared to be a single protein. This protein was electroblotted to nitrocellulose membrane, digested with trypsin, and selected peptides were isolated by HPLC and subjected to Edman microsequencing. The amino acid sequences of the peptides were found to be virtually identical to that of human neuron-specific enolase (NSE). A monoclonal antibody specific for human NSE confirmed the presence of this enzyme in the bovine IPM by both Western blotting and immunocytochemical analysis. Immunofluorescence microscopy demonstrated that NSE is mainly localized to the basal domain of the IPM surrounding photoreceptor cells but is also prominent in the inner segments of the cone photoreceptor neurons. When NSE was added to cultures of human retinoblastoma cells, no effect on morphology was observed. However, a positive effect on cell growth and/or survival was readily apparent. It thus seems that not only is NSE a significant component of the retinal extracellular matrix, but that it could function as a survival (neuronotrophic) factor for photoreceptor neurons.
Muscarinic receptors modulate N-, P-, and L-type Ca2+ currents in rat striatal neurons through parallel pathways
Authors: Howe AR , Surmeier DJ
Published: April 2018

Muscarinic modulation of calcium currents was studied in acutely isolated striatal neurons from the adult rat using the whole-cell configuration of the patch-clamp technique. Muscarinic agonists reduced calcium currents through two distinct signaling pathways. One pathway depended upon PTX-sensitive G-proteins and targeted N- and P-type currents. The other pathway depended upon PTX-insensitive G-proteins and was rendered inactive by high intracellular concentrations of BAPTA and targeted L-type currents. The modulation of N- and P-type currents was relieved by strong depolarizing prepulses, whereas the modulation of L-type currents was not. These findings support the proposition that parallel signaling pathways exist between muscarinic receptors and calcium channels.
Maintenance and degradation of proteins in intact and severed axons: implications for the mechanisms of long-term survival of anucleate crayfish axons
Authors: Tanner SL , Storm EE , Bittner GD
Published: April 2018

Protein maintenance and degradation are examined in the severed distal (anucleate) portions of crayfish medial giant axons (MGAs), which remain viable for over 7 months following axotomy. On polyacrylamide gels, the silver-stained protein banding pattern of anucleate MGAs severed from their cell bodies for up to 4 months remains remarkably similar to that of intact MGAs. At 7 months postseverance, some (but not all) proteins are decreased in anucleate MGAs compared to intact MGAs. To determine the half-life of axonally transported proteins, we radiolabeled MGA cell bodies and monitored the degradation of newly synthesized transported proteins. Assuming exponential decay, proteins in the fast component of axonal transport have an average half-life of 14 d in anucleate MGAs and proteins in the slow component have an average half-life of 17 d. Such half-lives are very unlikely to account for the ability of anucleate MGAs to survive for over 7 months after axotomy.
Regulation of c-ski transgene expression in developing and mature mice
Authors: Leferovich JM , Lana DP , Sutrave P , Hughes SH , Kelly AM
Published: April 2018

The control of c-ski transgene expression and muscle hypertrophy have been investigated in transgenic mice. In adult animals, the level of transgene expression is linked to the specialized phenotype of individual muscles, high levels occur in fast muscles and significantly lower levels in muscles with high metabolic activity (diaphragm, soleus). These findings have led us to propose that a threshold must be passed before ski-induced growth can occur. We now show that within fast muscles, induced hypertrophy uniquely involves IIb fibers. This pattern of expression is under development control; levels of c-ski mRNA are low in all muscles at birth. In the diaphragm, there is a sevenfold increase in c-ski message levels between 5 d and maturity. By contrast, in fast extensor digitorum longus and anterior tibial muscles, there is a 24-fold increase in levels between 5 and 12 d postpartum. Muscle hypertrophy and antibody staining for c-ski protein in myofiber nuclei emerge concurrently. This pattern of c-ski expression parallels the appearance of IIb myosin heavy chain transcripts (Wydert et al., 1987) and differentiation of IIb fibers, suggesting that amplification of c-ski mRNA levels is linked to the development of IIb fiber specialization. Manipulations that are known to perturb IIb fiber development, neonatal denervation, and neonatally induced hypothyroidism inhibit high levels of c-ski expression and hypertrophy. In the adult fast EDL, denervation leads to rapid atrophy of IIb fibers and a significant decline in levels of c-ski mRNA. The results suggest that the environment of differentiated IIb fibers permits the expression of high levels of c-ski mRNA and this, in turn, induces hypertrophy.
Relations between cortical and thalamic cellular events during transition from sleep patterns to paroxysmal activity
Authors: Steriade M , Contreras D
Published: April 2018

We investigated in anesthetized cats the progressive development from EEG-synchronized sleep patterns to low-frequency (< 15 Hz) paroxysmal activities, most of them consisting of epileptic-like seizures with spike-wave (SW) complexes at 2–4 Hz. We used multisite extra- and intracellular recordings of neocortical, reticular thalamic (RE), and thalamocortical (TC) neurons, including dual impalements of cortical and TC cells. A subsample (40%) of TC cells discharged spike bursts at 2–4 Hz, in close time relation with the spiky, depth-negative field components of SW seizures in related neocortical areas. Full synchronization among TC cells that were resonant with the cortical seizure activity was progressively reached toward the end of the SW paroxysm. The remaining TC cells (60%) were inhibited during the cortical SW seizures. We show that the duration and amplitude of hyperpolarization in TC cells paralleled the extent of cortical EEG paroxysm. Dual intracellular recordings of cortical and TC neurons demonstrate that during the cortical SW seizure, consisting of a tonic depolarization with superimposed paroxysmal spike bursts, the simultaneously recorded TC neurons displayed a tonic hyperpolarization associated with repetitive IPSPs, closely time related with cortical cell bursts. The inhibition of TC cells was presumably mediated by GABAergic RE thalamic neurons. Indeed, simultaneously recorded RE and TC neurons during the cortical SW paroxysm showed that cortical and RE cell excitation was accompanied by corresponding IPSPs in TC cells. We emphasize the progressive development from sleep patterns to some forms of epileptic-like activities. We propose that the inhibitory processes found in a significant number of TC cells during cortical SW seizures may contribute to the loss of consciousness, due to obliteration of synaptic transmission through the thalamus.
Functional synaptic connections made by regenerated retinal ganglion cell axons in the superior colliculus of adult hamsters
Authors: Sauve Y , Sawai H , Rasminsky M
Published: April 2018

Regenerated synaptic connections in the damaged mammalian visual system were studied in adult hamsters in which retinal ganglion cells (RGCs) regrew their axons through autologous peripheral nerve grafts directed from the stump of the transected optic nerve to the superior colliculus (SC). Unitary responses to illumination of small areas of the visual field were recorded within the superficial laminae of the reinnervated SC 23 to 60 weeks after grafting. Each element of a typical bursting response to light consisted of a terminal potential (TP) (half width 164 +/- 25 microseconds, amplitude up to 171 microV) arising from a regenerated RGC axon terminal arborization, followed at a latency of 268 +/- 63 microseconds by a longer duration negative focal synaptic potential (FSP) (half width 938 +/- 396 msec, amplitude up to 188 microV) reflecting EPSPs in neurons within the terminal field of the regenerated RGC axon. The FSP but not the TP was attenuated in a dose- dependent manner by iontophoretic application of GABA. In some cases spikes arose from FSPs after the first two or three impulses of a train, presumably reflecting summation of EPSPs to threshold for excitation in SC neurons contacted by the regenerated RGC axon terminals. Up to one-third of the area of the SC can be infiltrated by arborizations of the regenerated RGC axons that enter the SC through a nerve graft inserted in the lateral aspect of the SC. These experiments indicate that terminal arborizations of individual regenerated RGC axons can synapse with multiple neurons in the SC and that convergence of inputs from regenerated RGC axons is not required for activation of SC neurons in response to light.
Visual deprivation does not affect the orientation and direction sensitivity of relay cells in the lateral geniculate nucleus of the cat
Authors: Zhou Y , Leventhal AG , Thompson KG
Published: April 2018

Visual deprivation in early life profoundly affects the characteristic sensitivity of visual cortical cells to stimulus orientation and direction. Recently, relay cells in the lateral geniculate nucleus (LGNd) have been shown to exhibit significant degrees of orientation and direction sensitivity. The effects of visual deprivation upon these properties of subcortical cells are unknown. In this study cats were reared from birth to 6–12 months of age in total darkness; the orientation and direction sensitivities of area 17 (striate cortex) and LGNd cells were compared. All cells were studied using identical quantitative techniques and statistical tests designed to analyze distributions of angles. The results confirm previous work and indicate that the orientation and direction sensitivities of cells in area 17 are profoundly reduced by dark rearing. In marked contrast, these properties of LGNd relay cells are unaffected. The result is that, unlike in the normal cat, in dark-reared cats the orientation and direction sensitivities of cells in the LGNd and visual cortex do not differ. It is concluded that (1) the orientation and direction sensitivities of cortical cells contribute little, if at all, to the sensitivities of LGNd cells since LGNd cells exhibit normal sensitivities even though the cortical cells projecting to them exhibit greatly reduced sensitivities and (2) during normal development intracortical mechanisms appear to expand upon and/or modify the weak orientation and direction sensitivities of their inputs. These intracortical mechanisms depend upon normal visual experience since in dark-reared cats, but not normal ones, the orientation and direction sensitivities of cells in the LGNd and visual cortex do not differ quantitatively or qualitatively.
Conditioned fear-induced changes in behavior and in the expression of the immediate early gene c-fos: with and without diazepam pretreatment
Authors: Beck CH , Fibiger HC
Published: April 2018

The synthesis of Fos, the protein product of the immediate early gene c- fos, was used to map metabolically some of the neural substrates of conditioned fear in the rat. Analysis of the behaviors emitted by the rats during the test session provided strong evidence that the conditioning procedure was effective. Exposure to the environment in which they had previously received footshock significantly increased the number of Fos-like immunoreactive neurons in nearly 50 brain regions, both cortical and subcortical. Among the structures showing the most dramatic increases in fear-induced c-fos expression were the cingulate, piriform, infralimbic, and retrosplenial cortices, the anterior olfactory nucleus, claustrum, endopiriform nucleus, nucleus accumbens shell, lateral septal nucleus, various amygdalar nuclei, paraventricular thalamic nucleus, ventral lateral geniculate nucleus, the ventromedial, lateral, and dorsal hypothalamic nuclei, the ventral tegmental area, and the supramammillary area. These data demonstrate that a relatively simple classical conditioning procedure activates a large number of widely dispersed cortical and subcortical structures. Some of the structures showing increased c-fos expression have important autonomic functions and may therefore have reflected centrally mediated changes in blood pressure and respiration produced by the anxiogenic stimuli. In a second experiment, the effects of pretreatment with the anxiolytic drug diazepam (2.5, 5.0, or 10 mg/kg) were evaluated. The benzodiazepine produced dose-related decreases in the frequency of crouching (freezing) elicited by the aversively conditioned contextual cues. Diazepam also produced dose-related decreases in conditioned stress-induced c-fos expression in all but one structure, the effects being statistically significant in 38 of 60 sampled structures. Diazepam dose dependently increased fear-induced c- fos expression in the central nucleus of the amygdala. There was considerable regional variability with respect to sensitivity to diazepam, the retrosplenial cortex and the supramammillary area being the only two structures to show decreases after the lowest dose of diazepam. In contrast, the entorhinal cortex, nucleus accumbens core, ventromedial and posterior hypothalamic nuclei, median raphe, and locus coeruleus were particularly resistant to diazepam, all failing to show statistically significant decreases in conditioned fear-induced c-fos expression even at the highest dose. The extent to which diazepam decreased conditioned stress-induced c-fos expression was unrelated to previous estimates of benzodiazepine receptor density in the sampled structures.
Sigma ligands indirectly modulate the NMDA receptor-ion channel complex on intact neuronal cells via sigma 1 site
Authors: Yamamoto H , Yamamoto T , Sagi N , Klenerova V , Goji K , Kawai N , Baba A , Takamori E , Moroji T
Published: April 2018

To investigate the modulatory effects of sigma ligands on the N-methyl- D-aspartate (NMDA) receptor-ion channel complex in vivo, we examined the intact cell binding of 3H-N-[1-(2-thienyl)cyclohexyl]piperidine (3H- TCP) to cultured neuronal cells prepared from fetal rat telencephalon. The 3H-TCP binding was saturable, reversible, and inhibited by a selective NMDA receptor antagonist, D-amino-5-phosphonovaleric acid. MII-limolar Mg2+ inhibited 3H-TCP binding both in the absence and presence of L-glutamate. 5-Methyl-10,11-dihydro-5H-dibenzo [a,d]cyclohepten-5,10-imine maleate (MK801) inhibited 3H-TCP intact cell binding in a competitive manner, while haloperidol inhibited it in a noncompetitive manner. The effect of the test drugs to inhibit 3H-TCP intact cell binding was in the order of dextromethorphan, haloperidol > (+/-)MK 801 > (+)pentazocine > (-)pentazocine > DTG > PCP > (+)-N- allylnormetazocine [(+)SKF 10047] > (+)3-(3-hydroxyphenyl)-N- (1- propyl)piperidine [(+)3-PPP] > (-)SKF 10047 > (-)3-PPP. The IC50 values of the six sigma ligands for 3H-TCP binding were closely correlated with the Ki values of the corresponding drugs for DTG site 1 in the guinea pig brain reported by Rothman et al. (1991). These findings suggest that the sigma ligand indirectly modulates the NMDA receptor ion channel complex, presumably through sigma 1 sites in vivo as well as in vitro.
Delta and mu enkephalins inhibit spontaneous GABA-mediated IPSCs via a cyclic AMP-independent mechanism in the rat hippocampus
Authors: Lupica CR
Published: April 2018

The effects of enkephalins selective for delta and mu opioid receptors on inhibitory postsynaptic currents (IPSCs) mediated by GABA were studied in chloride-loaded CA1 pyramidal neurons in adult rat hippocampal slices. The mu agonist DAMGO (0.1 microM) significantly reduced the amplitudes of evoked monosynaptic IPSCs, recorded following the antagonism of excitatory glutamate receptors, and this effect was reversed by the mu antagonist CTOP (1 microM). The selective delta receptor agonists DPDPE and D-Ala2-deltorphin II (both 0.1–0.5 microM) had no effect on these evoked currents. In contrast, the frequency of tetrodotoxin-resistant spontaneous miniature GABA-mediated currents (m- IPSCs) was significantly reduced by both DPDPE (0.1–0.5 microM) and DAMGO (0.1–0.5 microM), while the amplitudes of these events were unaltered. These effects were reversed by the selective delta antagonist ICI 174,864 (1 microM) and the selective mu antagonist CTOP (1 microM), respectively. To investigate the mechanisms of this mu and delta receptor-mediated modulation of GABA release, and the possible involvement of a cAMP-sensitive K+ conductance, spontaneous action potential-dependent IPSCs (s-IPSCs) were measured following pretreatment with 8-bromo-cAMP (8-Br-cAMP). 8-Br-cAMP (250 microM) had no effect alone on the amplitude or frequency of s-IPSCs, nor did it alter the inhibitory effects of the delta and mu agonists. These results indicate that delta and mu opioid receptor activation inhibits spontaneous GABA release, independently of cAMP, through direct actions at inhibitory nerve terminals, and that delta opioids inhibit spontaneous but not evoked GABA release in the hippocampus.
Receptor encoding of moving tactile stimuli in humans. I. Temporal pattern of discharge of individual low-threshold mechanoreceptors
Authors: Edin BB , Essick GK , Trulsson M , Olsson KA
Published: April 2018

The response of 70 cutaneous, low-threshold mechanoreceptors in the human median, radial and inferior alveolar nerves to well controlled brush stimuli moving across the receptive field was quantitatively studied. Microneurography was used to obtain the response of each to multiple velocities from 0.5 to 32 cm/sec in at least two opposing directions. A high degree of response consistency was observed from the slowly adapting receptors to replication of the same stimulus and to a lesser, but significant degree from the fast adapting receptors. The evoked discharge reflected up to three partially overlapping phases of the moving stimulus: skin compression, indentation, and stretch. Although the overall discharge rate increased with both stimulus velocity and force, the spatial discharge pattern was preserved to a high degrees. In contrast, the discharge patterns differed for opposing and orthogonal directions. Reducing the area of skin surrounding the receptive field that was contacted by the moving stimuli had little effect on the evoked response. Individual mechanoreceptors display highly reliable differences to brush stimuli moving at different velocities. to brush stimuli moving at different velocities. Moreover, different directions of movement evoke differences in the discharge that are consistently observed upon replication of the same stimuli. Despite the richness and consistency in the spatial discharge pattern displayed by individual receptors, it is argued that the details of the patterns are not likely used by the CNS to infer information about direction and velocity of movement across the skin. Rather, the intensity of discharge is proposed as a plausible information-bearing attribute of the stimulus-evoked response.
Cortisol inhibition of calcium currents in guinea pig hippocampal CA1 neurons via G-protein-coupled activation of protein kinase C
Authors: ffrench-Mullen JM
Published: April 2018

The inhibition of voltage-activated Ca2+ channel currents by cortisol (hydrocortisone), the principal glucocorticoid in man and guinea pig, was examined in freshly dissociated pyramidal neurons from the adult guinea pig hippocampal CA1 region using whole-cell voltage-clamp recordings. Steady-state inhibition by cortisol of the peak Ca2+ channel current evoked by depolarization from -80 to -10 mV increased in a concentration-dependent fashion, with a maximal inhibition of 63 +/- 4% of the total current at 100 microM. Cortisone had a maximal 17 +/- 2% inhibition at 10 microM. Corticosterone and the metabolite allotetrahydrodeoxycorticosterone exhibited a plateau of inhibition of around 15% and 25%, respectively, between 10 pM and 100 nM; both compounds continued to inhibit at concentrations > 10(-7) M. Analysis of tail currents at -80 mV showed that cortisol and corticosterone had no effect on the voltage-dependent activation or deactivation of the Ca2+ channel current. However, cortisol slowed the activation of the current. Cortisol inhibited both the N-type or omega-conotoxin (CgTX)- sensitive, and the L-type or nifedipine (NIF)-sensitive Ca2+ channel current but had no effect on the CgTX/NIF-insensitive Ca2+ channel current. In neurons isolated from pertussis toxin (PTX)-treated animals, the cortisol inhibition was significantly diminished. Intracellular dialysis with GDP-beta-S (500 microM) or with the specific inhibitors of protein kinase C (PKC), the pseudosubstrate PKC inhibitor (PKCI 19–31) (2 microM) and bisindolylmaleimide (BIS) (1 microM) significantly diminished the cortisol inhibition of the Ca2+ channel current. The specific inhibitor of cAMP-dependent protein kinase (PKA) inhibitor, Rp-cAMPS (100 microM) had no effect.(ABSTRACT TRUNCATED AT 250 WORDS)
Differential expression of two cell surface proteins, neuropilin and plexin, in Xenopus olfactory axon subclasses
Authors: Satoda M , Takagi S , Ohta K , Hirata T , Fujisawa H
Published: April 2018

Immunohistochemistry by using monoclonal antibodies named A5 and B2, which specifically recognize cell surface proteins the neuropilin and the plexin, respectively, revealed that olfactory axons in Xenopus tadpoles were classified into several subgroups by virtue of the expression levels of these two cell surface molecules. The vomeronasal axons expressed the plexin but not the neuropilin. The plexin-positive and neuropilin-negative vomeronasal axons form a discrete fiber bundle, even after they joined with the principal olfactory axons. However, the principal olfactory axons were divided into at least two subclasses; the neuropilin-predominant axons which expressed high levels of the neuropilin and low levels of the plexin, and the plexin-predominant axons which expressed high levels of the plexin and low levels of the neuropilin. Within the olfactory nerve the pathways for these two principal olfactory axon subclasses were initially intermingled with each other, but were gradually segregated throughout their courses from the nose to the cerebrum. Eventually, the neuropilin-predominant and the plexin-predominant principal olfactory axon subclasses projected to specified glomeruli in topographically related regions within the main olfactory bulb. Neuroanatomical tracings of the olfactory projection also confirmed the gradual segregation of the pathways for the principal olfactory axons. These results allow us to speculate that both the neuropilin and the plexin are involved in axon interactions, and play roles in the organization of the precise patterns of the olfactory pathway and projection.
Motility and cytoskeletal organization of migrating cerebellar granule neurons
Authors: Rivas RJ , Hatten ME
Published: April 2018

To characterize CNS neuronal precursor migration along astroglial fibers, we examined the motility of the migratory leading process and cytoskeletal-based mechanisms of locomotion of early postnatal mouse cerebellar granule neurons in vitro. To visualize the surface motility of the leading process, granule neurons were labeled with the fluorescent lipophilic dye, PKH-26, and imaged by time lapse fluorescence microscopy. The motile behavior and cytoskeletal organization of the migrating neuron had several distinctive features. As the migrating neuron moved along the glial fiber, the leading process rapidly extended, projecting up to 40 microns, and retracted, withdrawing towards the cell soma. Broad lamellipodia were common along the entire length of the leading process, giving it a ruffled appearance. Within the cell soma, a cage-like distribution of microtubules encircled the nucleus and actin filaments formed a subcortical rim underneath the plasma membrane. Disruption of actin filaments with cytochalasin B inhibited migration, suggesting involvement of actin subunit assembly in neuronal migration. Both microtubules and actin filaments were heavily concentrated in the leading process; the leading process did not show the development of a distinct actin-rich domain at its tip.
Genetic transformation of the synaptic pattern of a motoneuron class in Caenorhabditis elegans
Authors: Walthall WW , Plunkett JA
Published: April 2018

Caenorhabditis elegans possesses two classes of inhibitory locomotory neurons, the DD and VD motoneurons (mns), and they form complementary components of a cross-inhibitory neuronal network innervating dorsal and ventral body muscles. The DD and VD mns (collectively called the D mns) share a number of morphological and neurochemical features, and mutations in a number of different genes disrupt both cell types in identical ways; however, the DD and VD mns have different lineal origins and different synaptic patterns. Given the number of phenotypic features shared by the D mns, it was of interest to determine what is responsible for the synaptic patterns that distinguish them. An analysis of the locomotory defect along with a genetic epistasis test suggested that unc-55 mutations alter the function of the VD but not the DD mns. Correlated with the defective locomotory behavior of unc-55 mutants was an alteration in the distribution of varicosities, structures associated with presynaptic elements, on the VD mns. The pattern of varicosities of the unc-55 VD mns resembled that of the wild- type DD mns. Moreover, the selective removal of the DD mns revealed that unc-55 VD mns had adopted a functional role appropriate for the DD mns. Thus, unc-55 appears to be involved in producing the synaptic patterns that distinguish the two D mn classes from one another; when the gene is mutated the VD and DD mns become structurally similar and functionally equivalent.
Language-related field potentials in the anterior-medial temporal lobe: I. Intracranial distribution and neural generators
Authors: McCarthy G , Nobre AC , Bentin S , Spencer DD
Published: April 2018

Field potentials were recorded from intracranial electrodes in humans to study language-related processing. Subjects viewed sentences in which each word was presented successively in the center of a video monitor. Half of the sentences ended normally, while the other half ended with a semantically anomalous word. The anomalous sentence-ending words elicited a large negative field potential with a peak latency near 400 msec, which was focally distributed bilaterally in the anterior medial temporal lobe (AMTL), anterior to the hippocampus and near the amygdala. Subdural electrodes positioned near the collateral sulcus just inferior and lateral to the amygdala recorded a positive field potential at the same latency. This spatial distribution of voltage suggested that this language-sensitive field potential was generated in the neocortex near the collateral sulcus and anterior fusiform gyrus. Additional task-related field potentials were recorded in the hippocampus. The AMTL field potential at 400 msec shares characteristics with the N400 potential recorded from scalp electrodes that has been associated with semantic processing.
Language-related field potentials in the anterior-medial temporal lobe: II. Effects of word type and semantic priming
Authors: Nobre AC , McCarthy G
Published: April 2018

Field potentials were recorded from intracranial electrodes in humans to study the role of the anterior medial temporal lobe (AMTL) in language-related processing. Subjects viewed lists of words in which orthography and word type varied, or in which words were primed by semantic associates. Large negative field potentials were elicited within the AMTL by isolated words. The amplitude and intracranial distribution of these AMTL field potentials were consistent with those in our previous study in which anomalous sentence-ending words were used as stimuli (McCarthy et al., in press). The neocortex, in the region of the collateral sulcus and anterior fusiform gyrus, was identified as the likely neural generator of this field potential. The AMTL field potential was diminished by semantic priming, and was larger for words with semantic content than for words serving grammatical function. Orthographically illegal nonwords did not elicit this field potential. The N400 scalp event-related potential (ERP) has been shown to respond in the same manner to these task manipulations (Nobre and McCarthy, 1994), and, thus, the AMTL field potential was proposed to contribute to the generation of N400. The possible roles in language processing reflected by the AMTL field potential were considered.