bluuebunny/crossref_metadata_2025 huggingface dataset:
A model for the development of simple cell receptive fields and the ordered arrangement of orientation columns through activity-dependent competition between ON- and OFF-center inputs
Authors: Miller KD
Published: April 2018

Neurons in the primary visual cortex of higher mammals respond selectively to light/dark borders of a particular orientation. The receptive fields of simple cells, a type of orientation-selective cell, consist of adjacent, oriented regions alternately receiving ON-center and OFF-center excitatory input. I show that this segregation of inputs within receptive fields can occur through an activity-dependent competition between ON-center and OFF-center inputs, just as segregation of inputs between different postsynaptic cells into ocular dominance columns appears to occur through activity-dependent competition between left-eye and right-eye inputs. These different outcomes are proposed to result, not from different mechanisms, but from different spatial structures of the correlations in neural activity among the competing inputs in each case. Simple cells result if ON-center inputs are best correlated with other ON-center inputs, and OFF with OFF, at small retinotopic separations, but ON-center inputs are best correlated with OFF-center inputs at larger separations. This hypothesis leads robustly to development of simple cell receptive fields selective for orientation and spatial frequency, and to the continuous and periodic arrangement of preferred orientation across the cortex. Input correlations determine the mean preferred spatial frequency and degree of orientation selectivity. Estimates of these correlations based on measurements in adult cat retina (Mastronarde, 1983a,b) produce quantitative predictions for the mean preferred spatial frequencies of cat simple cells across eccentricities that agree with experiments (Movshon et al., 1978b). Intracortical interactions are the primary determinant of cortical organization. Simple cell spatial phases can play a key role in this organization, so arrangements of spatial phases and preferred orientations may need to be studied together to understand either alone. Possible origins for other cortical features including spatial frequency clusters, afferent ON/OFF segregation, blobs, pinwheels, and opponent inhibition within simple cell receptive fields are suggested. A number of strong experimental tests of the hypothesis are proposed.
Different kinetics govern dopaminergic transmission in the amygdala, prefrontal cortex, and striatum: an in vivo voltammetric study
Authors: Garris PA , Wightman RM
Published: April 2018

The regulation of extracellular dopamine (DA) concentrations was examined and compared in vivo in four projection fields of mesotelencephalic dopaminergic neurons with fast-scan cyclic voltammetry at carbon-fiber microelectrodes. Transient electrical stimulation of ascending DA fibers in a near physiological range of frequencies (10–20 Hz) elicited similar levels of extracellular DA in the medial prefrontal cortex (MPFC), basal lateral amygdaloid nucleus (BAN), caudate-putamen (CP), and nucleus accumbens (NAc) despite the documented 90-fold disparity in DA tissue levels and terminal density. However, marked differences were observed in the dynamics and overall frequency dependence of the evoked synaptic overflow of DA. These differences are due to the significantly different rates of release and uptake found in each of the four regions. For example, rate constants for the release of the four regions. For example, rate constants for the release and uptake of DA were similar in the MPFC and BAN but approximately 8 and 50 times less, respectively, than that in the CP and NAc. When the parameters were normalized to endogenous DA tissue content, a unique picture emerged: compared to all other regions, relative release was 10-fold greater in the MPFC while relative uptake was at least 10 times less in the BAN. The results further differentiate the functional characteristics of mesotelencephalic dopaminergic systems and demonstrate the regiospecific nature of DA neural transmission in the brain. In addition, the regulation of extracellular DA levels in the MPFC and BAN is suitable for the “long- range” transfer of chemical information in the brain and is consistent with a hypothesis of extrasynaptic neurotransmission.
Asymmetric expression of a novel homeobox gene in vertebrate sensory organs
Authors: Deitcher DL , Fekete DM , Cepko CL
Published: April 2018

A novel homeobox gene, SOHo-1, was isolated from embryonic chicken retina. On embryonic day 2 (E2), SOHo-1 is expressed in the retina, posterolateral otic pit, and neural tube anterior to the spinal cord. On E4, SOHo-1 is expressed at high levels in anterior retina and low levels in posterior retina, suggestive of a role in patterning the anterior-posterior axis. It is also expressed on E4 in the otocyst, the dorsal root ganglia, some cranial ganglia, and the second branchial arch. SOHo-1 expression in the otic pit and otocyst is restricted to regions that will give rise to the nonsensory tissues of the inner ear. SOHo-1 is not closely related to any identified vertebrate or Drosophila homeobox-containing genes. Since it is expressed in sensory- related structures and does not fit into existing classes of homeobox genes, we propose the name SOHo-1, for sensory organ homeobox-1.
Kv3.3b: a novel Shaw type potassium channel expressed in terminally differentiated cerebellar Purkinje cells and deep cerebellar nuclei
Authors: Goldman-Wohl DS , Chan E , Baird D , Heintz N
Published: April 2018

A two-step hybridization/subtraction procedure was employed to isolate markers for the later stages of Purkinje cell differentiation. From this screen, a novel Shaw potassium channel cDNA (Kv3.3b) was identified that is developmentally regulated. Expression of this channel is highly enriched in the brain, particularly in the cerebellum, where its expression is confined to Purkinje cells and deep cerebellar nuclei. Sequence analysis revealed that it is an alternatively spliced form of the mouse Kv3.3 gene, and that the previously reported Kv3.3 mRNA (Ghanshani et al., 1992) is not expressed in cerebellum. Expression of the Kv3.3b mRNA begins in cerebellar Purkinje cells between postnatal day 8 (P8) and P10 and continues through adulthood, coinciding with elaboration of the mature Purkinje cell dendritic arbor. The timing of expression of Kv3.3b mRNA is maintained in mixed, dissociated primary cerebellar cell culture. These results suggest that the Kv3.3b K+ channel function is restricted to terminally differentiated Purkinje cells, and that analysis of the mechanisms governing its expression in vivo and in vitro can reveal molecular mechanisms governing Purkinje cell differentiation.
Enhancement of voltage-gated Ca2+ currents induced by daily stimulation of hippocampal neurons with glutamate
Authors: Garcia DE , Cavalie A , Lux HD
Published: April 2018

The regulation of calcium channel currents (ICa) induced by daily stimulation (1 hr) with 10 microM glutamate was studied in full differentiated hippocampal cells in culture. We report a specific enhancement of the high-voltage-activated current type (HVA ICa) ongoing over days. The density of HVA ICa increased about twofold after the second glutamate session, and this enhancement was still observed after the fifth day of treatment, while low-voltage-activated calcium currents (LVA ICa) remained unchanged. During glutamate application, a transient increase of intracellular calcium (Cai) was observed, followed by a slow decay within 2–3 min, and substantial recovery in about 10 min. Similarly, Cai transients induced by periodic membrane depolarization mimicked the long-term effect of glutamate on ICa. These results demonstrate for the first time an increase of ICa in a time frame of days. Since the effect of glutamate on ICa was prevented by cycloheximide, neosynthesis of channel proteins presumably supports this enhancement.
Visual search among items of different salience: removal of visual attention mimics a lesion in extrastriate area V4
Authors: Braun J
Published: April 2018

In more than one respect, visual search for the most salient or the least salient item in a display are different kinds of visual tasks. The present work investigated whether this difference is primarily one of perceptual difficulty, or whether it is more fundamental and relates to visual attention. Display items of different salience were produced by varying either size, contrast, color saturation, or pattern. Perceptual masking was employed and, on average, mask onset was delayed longer in search for the least salient item than in search for the most salient item. As a result, the two types of visual search presented comparable perceptual difficulty, as judged by psychophysical measures of performance, effective stimulus contrast, and stability of decision criterion. To investigate the role of attention in the two types of search, observers attempted to carry out a letter discrimination and a search task concurrently. To discriminate the letters, observers had to direct visual attention at the center of the display and, thus, leave unattended the periphery, which contained target and distractors of the search task. In this situation, visual search for the least salient item was severely impaired while visual search for the most salient item was only moderately affected, demonstrating a fundamental difference with respect to visual attention. A qualitatively identical pattern of results was encountered by Schiller and Lee (1991), who used similar visual search tasks to assess the effect of a lesion in extrastriate area V4 of the macaque.
Glutamate-evoked release of arachidonic acid from mouse brain astrocytes
Authors: Stella N , Tence M , Glowinski J , Premont J
Published: April 2018

Brain astrocytes in primary culture from the rat or the mouse have been shown to possess ionotropic and metabotropic glutamatergic receptors. The activation of both types of receptors is responsible for a rise in the cytosolic concentration of calcium, while the stimulation of metabotropic receptors induces the accumulation of inositol phosphates. In the present study, it is demonstrated that in striatal astrocytes from mouse embryos, glutamate evokes a release of arachidonic acid. The nonionotropic receptors involved in this effect appeared to be pharmacologically distinct from those coupled to phospholipase C: (1) glutamate displayed different dose-response curves for the production of inositol phosphates (biphasic: EC50 = 25 and 300 microM) and the release of arachidonic acid (monophasic: EC50 = 200 microM); (2) L(+)-2- amino-4-phosphonobutyric acid (AP4) only antagonized the glutamate- evoked release of arachidonic acid without altering the production of inositol phosphates; (3) when used at a concentration of 0.1 mM, quisqualate induced a higher formation of inositol phosphates than glutamate (2 mM) while, in contrast to glutamate, it only weakly stimulated arachidonic acid release when used either at 0.1 mM or 1 mM. L(+)-2-amino-3-phosphonopropionic acid (AP3) suppressed both responses. The glutamate-evoked release of arachidonic acid seems to be oppositely regulated by protein kinases A and C. Indeed, the stimulation of adenylate cyclase by the beta-adrenergic agonist isoproterenol, vasoactive intestinal peptide, or pretreatment of striatal astrocytes with cholera toxin decreased the glutamate-evoked release of arachidonic acid. In contrast, ATP, which markedly stimulated inositol phosphate production, strongly potentiated the glutamate-evoked release of arachidonic acid.(ABSTRACT TRUNCATED AT 250 WORDS)
Input-output organization of the sensorimotor striatum in the squirrel monkey
Authors: Flaherty AW , Graybiel AM
Published: April 2018

The basal ganglia receive massive inputs from the neocortex and send outputs that exert both inhibitory and disinhibitory control over parts of the frontal cortex and brainstem. Between these basal ganglia inputs and outputs lies the striatum, which receives most of the cortical afferents and projects to the basal ganglia output nuclei--the globus pallidus and substantia nigra. To analyze this system we conjointly labeled, in squirrel monkeys, sensorimotor cortical inputs to the striatum and striatal outputs to the globus pallidus. Anterograde tracers were injected into the motor (MI) and somatosensory (SI) cortical body maps, at sites determined by electrophysiological stimulation and recording. Retrograde tracers were stereotaxically injected into the external and internal pallidal segments (GPe and GPi). We found that multiple dispersed modules (“matrisomes”) in the putamen that all received inputs from single body-part representations in sensorimotor cortex could, in turn, send convergent outputs to single sites in the pallidum. This divergence-reconvergence pattern was found for both GPe and GPi sites, and for inputs from both SI and MI cortex. Thus, information from a single functional region in the cortex can be split up at the striatal stage only to be brought back together in the pallidum. The temporary divergence may increase lateral interactions between sensorimotor matrisomes, as well as between matrisomes and striosomes. One function of striatal modularity may thus be to set up an associative network in the striatum, which might contribute to sensorimotor learning. We also found that some sets of matrisomes did not receive strong sensorimotor inputs, even though they projected to regions of GPe and GPi that are near the sensorimotor- recipient zones described above. Thus, the matrisomal system may sort MI/SI inputs and other inputs before transfer to paired regions of GPe and GPi.
Presynaptic calcium is increased during normal synaptic transmission and paired-pulse facilitation, but not in long-term potentiation in area CA1 of hippocampus
Authors: Wu LG , Saggau P
Published: April 2018

We examined the relationship between presynaptic calcium levels and postsynaptic potentials during normal synaptic transmission, paired- pulse facilitation (PPF), and long-term potentiation (LTP) in CA3-CA1 synapses of hippocampus. By selectively loading the presynaptic terminals with the calcium indicator fura-2, we simultaneously recorded a presynaptic calcium (Ca) transient and the corresponding field EPSP evoked by a single stimulus given to the Schaffer collateral- commissural pathway in guinea pig hippocampal slices. A volume average presynaptic Ca influx was obtained by taking the first time derivative of the Ca transient. Our data indicate that the synaptic transmission represented by the initial slope of the field EPSP is approximately proportional to the fourth power of the presynaptic Ca influx, the volume average Ca current. Our results in combination with similar findings at the squid giant synapse (Augustine et al., 1985b; Augustine and Charlton, 1986) suggest that the relationship between Ca influx and transmitter release is well conserved from the molluscan to the mammalian nervous system. A transient increase of the residual Ca level ([Ca]res) is generally thought to be the mechanism underlying PPF (Katz and Miledi, 1968; Charlton et al., 1982); however, the relationship between PPF and the presynaptic [Ca]res had not been examined before. Our results demonstrate that PPF is approximately linearly related to the [Ca]res. This finding further supports the residual Ca hypothesis for PPF. Accumulated evidence from other groups suggests that the presynaptic site contributes to the maintenance of LTP in CA3-CA1 synapses (Bekkers and Stevens, 1990; Malinow and Tsien, 1990); however, our data show that neither an increase of the Ca transient nor a sustained increase of the [Ca]res occurs in the presynaptic terminals during maintenance of LTP. This suggests that the presynaptic mechanism underlying LTP must be downstream to Ca influx.
Network analysis of cortical visual pathways mapped with PET
Authors: McIntosh AR , Grady CL , Ungerleider LG , Haxby JV , Rapoport SI , Horwitz B
Published: April 2018

Brain metabolic mapping techniques, such as positron emission tomography (PET), can provide information about the functional interactions within entire neural systems. With the large quantity of data that can accumulate from a mapping study, a network analysis, which makes sense of the complex interactions among neural elements, is necessary. A network analysis was performed on data obtained from a PET study that examined both the changes in regional cerebral blood flow (rCBF) and interregional correlations among human cortical areas during performance of an object vision (face matching) and spatial vision (dot- location matching) task. Brain areas for the network were selected based on regions showing significant rCBF or interregional correlations between tasks. Anterior temporal and frontal lobe regions were added to the network using a principal components analysis. Interactions among selected regions were quantified with structural equation modeling. In the structural equation models, connections between brain areas were based on known neuroanatomy and the interregional correlations were used to calculate path coefficients representing the magnitude of the influence of each directional path. The combination of the anatomical network and interregional correlations created a functional network for each task. The functional network for the right hemisphere showed that in the object vision task, dominant path influences were among occipitotemporal areas, while in the spatial vision task, occipitoparietal interactions were stronger. The network for the spatial vision task also had a strong feedback path from area 46 to occipital cortex, an effect that was absent in the object vision task. There were strong interactions between dorsal and ventral pathways in both networks. Functional networks for the left hemisphere did not differ between tasks. Networks for the interhemispheric interactions showed that the dominant pathway in the right hemisphere also had stronger effects on homologous left hemisphere areas and are consistent with a hypothesis that intrahemispheric interactions were greater in the right hemisphere in both tasks, and that these influences were transmitted callosally to the left hemisphere.
Immunocytochemical evidence that neurotensin is present in glutamatergic neurons in the superficial dorsal horn of the rat
Authors: Todd AJ , Spike RC , Price RF , Neilson M
Published: April 2018

In order to determine whether glutamate is enriched in neurotensin- containing axons in the superficial dorsal horn of the rat spinal cord, we have carried out preembedding immunocytochemistry with an antiserum to neurotensin and then used a postembedding immunogold method with antiserum to glutamate. The immunogold label (corresponding to glutamate-like immunoreactivity) over 40 neurotensin-immunoreactive boutons in laminae I and II of the lumbar dorsal horn was compared with that over nearby axons that formed asymmetrical or symmetrical synapses. In addition, for 20 of these boutons, the labeling was compared with that over mossy and parallel fiber terminals (both of which are thought to use glutamate as a transmitter) from sections of cerebellum that had been processed together with those of spinal cord. Glutamate-like immunoreactivity was consistently high over neurotensin- immunoreactive boutons relative to most surrounding profiles. Immunostaining over these boutons was slightly (11%) lower than that over matched terminals that formed asymmetrical synapses, but considerably higher than that over the terminals that formed symmetrical synapses. The level of glutamate immunoreactivity in neurotensin-immunoreactive boutons in dorsal horn was similar to that in cerebellar parallel fiber terminals, but significantly lower than that in mossy fiber terminals. These results suggest that glutamate is a transmitter used by neurotensin-immunoreactive axons in the dorsal horn, and since these axons are thought to be largely or entirely derived from neurotensin-containing neurons in laminae I-III, they provide immunocytochemical evidence for a population of excitatory glutamatergic neurons in this region.
The role of the cytoplasmic domains of individual subunits of the acetylcholine receptor in 43 kDa protein-induced clustering in COS cells
Authors: Yu XM , Hall ZW
Published: April 2018

The 43 kDa protein, a cytoplasmic peripheral membrane protein, is closely associated with the acetylcholine receptor (AChR) at the neuromuscular junction, where it is thought to anchor the receptor in the postsynaptic membrane. We have used the 43 kDa protein-induced clustering of AChRs that occurs when both proteins are transiently expressed in COS cells to investigate which parts of the AChR might interact with the 43 kDa protein. By constructing chimeric subunits, we showed that the cytoplasmic domains of neither the epsilon nor delta subunits are required for 43 kDa protein-induced clustering. Systematic mutational analysis of the long cytoplasmic loops of the alpha and beta subunits showed that most of the loops can be altered without affecting the ability of the AChR to be clustered; in each case, however, one or more sequences could not be tested, because mutation in these regions prevented AChR assembly. Our results suggest either that these regions are involved in clustering or that the 43 kDa protein can interact with multiple, alternative sites on the cytoplasmic surface of the AChR. Our experiments also show that the postulated sites of tyrosine phosphorylation in the beta subunit and of serine phosphorylation in the alpha subunit can be mutated without affecting 43 kDa protein- induced AChR clustering.
Microtubule-associated protein 1b (MAP1b) is concentrated in the distal region of growing axons
Authors: Black MM , Slaughter T , Fischer I
Published: April 2018

Microtubule-associated protein 1b (MAP1b) is expressed at especially high levels in neurons actively extending axons, and although it appears to be required for axon growth, the nature of its role is unknown. We reasoned that a detailed description of the localization of MAP1b in growing axons would help define how MAP1b participates in axon growth. Therefore, we have stained cultured sympathetic neurons with various antibodies against MAP1b, and then used digital image processing and analysis procedures to quantify MAP1b distribution, phosphorylation and association with microtubules (MTs) in actively elongating axons. MAP1b is present on MTs all along the axon. Quantitative analyses showed that MAP1b has a nonuniform distribution along growing axons. It is present at relatively low and constant levels along the axon shaft until approximately 130 microns from the axon tip, where the amount of MAP1b begins to increase sharply and reaches a peak close to the growth cone. The peak amount of MAP1b in the distal axon is an order of magnitude greater than the average amount in the axon shaft. The enrichment of MAP1b in the distal axon was observed for total MAP1b and assembled MAP1b, and was even more pronounced for phosphorylated MAP1b. This distribution pattern remains after correcting the relative amount of MAP1b along the axon for variations in axonal volume. Thus, the concentration of MAP1b in the distal axon exceeds by severalfold that in the rest of the axon. The amount of assembled MAP1b relative to the amount of MT polymer also varies along the axon, and is greatest distally near the growth cone. This pattern of MAP1b localization in axons focuses attention on the distal axon and growth cone as the principal sites of MAP1b function in axon growth. We discuss the possibility that MAP1b regulates MT dynamics in the distal axon so that it is properly coordinated with growth cone events involved in axon extension.
A functional anatomical analysis of central pathways subserving the effects of interleukin-1 on stress-related neuroendocrine neurons
Authors: Ericsson A , Kovacs KJ , Sawchenko PE
Published: April 2018

Systemic administration of the cytokine interleukin-1 (IL-1) results in increased secretion of ACTH and corticosterone in rats. The available evidence suggests that the acute effects of IL-1 are exerted ultimately at the level of the hypothalamus to increase corticotropin-releasing factor (CRF) secretion into the hypophyseal portal circulation, and hence the central drive on the pituitary-adrenal system. However, the route(s) and mechanism(s) by which circulating IL-1 gains access to central mechanisms governing pituitary-adrenal output remain poorly understood. In this study, we show that intravenous injection of IL-1 beta provokes time- and dose-dependent increases in the expression of the immediate-early gene c-fos, in identified CRF and oxytocin- producing cells of the paraventricular nucleus of the hypothalamus (PVH). Several cell groups known to be involved in central visceromotor regulation also displayed comparable time- and dose-related activation to systemic IL-1, including the bed nucleus of the stria terminalis, the central nucleus of the amygdala, the lateral parabrachial nucleus, and cell groups of the dorsomedial and ventrolateral medulla. Activation of circumventricular organs, which have been hypothesized to serve as central monitors of circulating IL-1, required doses roughly an order of magnitude above those required to activate CRF neurons in the PVH. Combined immunohistochemical and retrograde tracing experiments revealed many IL-1-responsive cells in the nucleus of the solitary tract and the ventrolateral medulla to be catecholaminergic and to project to the region of the PVH. Discrete and unilateral interruption of ascending catecholaminergic projections from the medulla attenuated IL-1-stimulated increases in Fos immunoreactivity and CRF mRNA in the PVH on the ipsilateral side. Disruption of descending projections from circumventricular structures associated with the lamina terminalis did not affect IL-1-mediated Fos induction in the PVH. We conclude that medullary catecholaminergic projections to the PVH play either a mediating or a permissive role in the IL-1- induced activation of the central limb of the hypothalamo-pituitary- adrenal axis.
Opioids mobilize calcium from inositol 1,4,5-trisphosphate-sensitive stores in NG108-15 cells
Authors: Jin W , Lee NM , Loh HH , Thayer SA
Published: April 2018

Opioids elicit an increase in the intracellular free Ca2+ concentration ([Ca2+]i) in neuroblastoma x glioma hybrid NG108–15 cells, which, depending upon growth conditions, results from either Ca2+ influx in differentiated cells or Ca2+ release from internal stores in undifferentiated cells (Jin et al., 1992). In this report we describe fura-2-based digital imaging studies that demonstrate that opioid- evoked Ca2+ release in these cells results from the activation of phospholipase C (PLC) and subsequent mobilization of the inositol 1,4,5- trisphosphate (IP3)-sensitive store. D-Ala2-D-Leu5-enkephalin (DA-DLE) evoked concentration-dependent increases in [Ca2+]i (EC50 approximately equal to 4 nM). The response was blocked by naloxone (1 microM). In single cells, sequential application of selective opioid agonists (10 nM) evoked responses of the rank order DADLE = D-Pen2, D-Pen5- enkephalin (DPDPE) > trans-(+/-) 3,4-dichloro-N-methyl-N-(2-[1- pyrrolidinyl]cyclohexyl) benzeneacetamide (U50488) > D-ala2, N-Me-Phe4, Gly5-ol-enkephalin (DAMGO), consistent with activation of a delta- opioid receptor. Forty percent (n = 198) of the cells responded to 100 nM DADLE with a net [Ca2+]i increase of 483 +/- 40 nM. Bradykinin (100 nM) elicited a response in 91% of the cells with a mean net amplitude of 707 +/- 36 nM. The DADLE-evoked responses were not blocked by removal of extracellular Ca2+; instead, they were abolished by treatment with 10 nM thapsigargin, an agent that depletes and prevents refilling of IP3-sensitive Ca2+ stores. A 1 microM concentration of U73122, an aminosteroid inhibitor of PLC, completely blocked the DADLE- evoked [Ca2+]i increase, while an inactive analog, U73433, was without effect. To explore the possible role of G-proteins in mediating opioid- induced [Ca2+]i increases in NG108–15 cells, we pretreated cells with pertussis or cholera toxin; pertussis toxin blocked the opioid-induced response while cholera toxin was without effect, consistent with a Gi- or Go-mediated effect. Activation of the opioid inhibitory pathway previously described for these cells appears to stimulate the phosphoinositide (PI) cascade as well. Including the PI cascade among the multiple second messenger systems modulated by opioids may be key to understanding the biochemical events that underlie acute and chronic opioid action.
Axons regulate Schwann cell expression of the POU transcription factor SCIP
Authors: Scherer SS , Wang DY , Kuhn R , Lemke G , Wrabetz L , Kamholz J
Published: April 2018

SCIP (suppressed cAMP-inducible POU) is a POU domain transcription factor expressed by Schwann cells. Drugs that elevate intracellular cAMP, such as forskolin, increase the expression of SCIP and partially mimic the inductive effects of axons on Schwann cell gene expression. Thus, SCIP may be involved in a differentiation pathway in Schwann cells that is activated by axons. We have examined this issue by studying SCIP expression in developing, degenerating, and regenerating rat peripheral nerves, and in Schwann cell-neuron cocultures. High levels of SCIP mRNA were detected in developing and regenerating nerves, and axotomy at these times caused the level of SCIP mRNA to plummet. Similarly, there were many SCIP-immunoreactive Schwann cell nuclei in developing and regenerating nerves, and their number fell sharply after axotomy. SCIP-immunoreactive Schwann cells were associated with axons in developing and regenerating nerves, and in Schwann cell-neuron cocultures. These data demonstrate that axons upregulate the expression of SCIP in Schwann cells, and that SCIP is expressed in Schwann cells that ensheathe axons. Thus, SCIP may mediate some of the changes in Schwann cell gene expression that accompany axonal ensheathment.
Regulation of a periodic motor program in C. elegans
Authors: Liu DW , Thomas JH
Published: April 2018

A three-part motor program mediates a defecation every 45 sec in well- fed wild-type Caenorhabditis elegans. Individual worms maintain this 45 sec rhythm with an SD of about 3 sec. We present evidence that the defecation cycle is controlled by an endogenous clock, most likely a neuronal pattern generator. The phase of the behavioral rhythm can be reset like pattern generators in other animals. The rhythm was reset by stimulating a well-characterized neuronal circuit mediating response to light touch. Also, animals that spontaneously stopped feeding interrupted their defecation rhythms. When they resumed feeding these animals reactivated the motor program in phase with the previously established rhythm, indicating that an endogenous clock continues to run even when the behavior is not expressed. Control of the defecation rhythm is independent of expression of the motor program. Most previously isolated mutations that affect the motor program (Thomas, 1990) do not alter the rhythm of the behavior; the motor steps themselves are defective but not the timing of their activation. Laser kills of identified motor neurons that affect particular parts of the motor program also did not change the defecation rhythm. Another sensory stimulus, food, strongly modulates defecation behavior: animals away from food rarely activated the motor program, and food dilution resulted in a graded lengthening of the cycle period. To elucidate further the relationship between feeding and defecation rhythms we studied a mutation, dec-8(sa200), that caused worms to continue to activate the motor program in the absence of food. The mutant did not require the presence of food to activate the motor program, although food made the rhythm more precise. In the presence of food, dec- 8(sa200) animals exhibited tandem activations of the defecation motor program; the principal activation was followed by a more variable second activation. Further experiments suggested that the tandem activations of the motor program are not due to the activity of multiple oscillators.
In the rat, endogenous nitric oxide modulates the response of the hypothalamic-pituitary-adrenal axis to interleukin-1 beta, vasopressin, and oxytocin
Authors: Rivier C , Shen GH
Published: April 2018

Nitric oxide (NO) synthase (NOS), the enzyme responsible for NO formation, is found in hypothalamic neurons containing oxytocin (OT), vasopressin (VP), and to a lesser extent corticotropin-releasing factor (CRF). Because NO is reported to modulate endocrine activity, we have investigated the hypothesis that endogenous NO participates in ACTH released by various secretagogues in the rat. In the adult male rat, the intravenous injection of interleukin-1 beta (IL-1 beta; 0.2–0.3 micrograms/kg), VP (0.3–0.9 micrograms/kg), and OT (30 micrograms/kg) significantly increased plasma ACTH and corticosterone levels. Pretreatment with the L-form, but not the D-form, of N omega nitro-L- arginine-methylester (L-NAME; a specific inhibitor of NOS) markedly augmented the effects of these secretagogues whether it was injected acutely or over a 4 d period. Blockade of NOS activity also caused significant (P < 0.01) extensions of the duration of action of IL-1 beta, VP, and OT. In contrast, L-NAME did not significantly alter the stimulatory action of peripherally injected CRF, or centrally administered IL-1 beta. Administration of L-arginine, but not D- arginine (100 mg/kg), used as a substrate for basal NO synthesis and which did not by itself alter the activity of the hypothalamic- pituitary-adrenal (HPA) axis, blunted IL-1-induced ACTH secretion, and reversed the interaction between L-NAME and IL-1 beta. The stimulatory action of endotoxin, a lipopolysaccharide that releases endogenous cytokines, was also augmented by inhibition of NO formation.(ABSTRACT TRUNCATED AT 250 WORDS)
A biphasic change in ribosomal conformation during transneuronal degeneration is altered by inhibition of mitochondrial, but not cytoplasmic protein synthesis
Authors: Garden GA , Canady KS , Lurie DI , Bothwell M , Rubel EW
Published: April 2018

Following loss of eighth nerve input, 20–40% of neurons in the neonatal chick cochlear nucleus, nucleus magnocellularis (NM), undergo cell death. Intracellular changes that precede the death of NM neurons include increased oxidative metabolism and mitochondrial volume, decreased cytoplasmic protein synthesis, and destruction of ribosomes. Six hours following afferent deprivation, dying NM neurons demonstrate complete loss of ribosomes and cessation of protein synthesis, suggesting that the rapid destruction of ribosomes leads to neuronal death. Increased NM neuron death occurs when mitochondrial upregulation is prevented by chloramphenicol, a mitochondrial protein synthesis inhibitor. This finding suggests that increased oxidative capacity is required for neuronal survival following loss of afferent input. To study changes in the ribosomes of afferent-deprived NM neurons, we obtained a monoclonal antibody to ribosomal RNA. This monoclonal antibody, Y10B, labels ribosomes of all NM neurons receiving normal synaptic activity. Following removal of afferent input, NM neurons demonstrate a biphasic change in their pattern of Y10B label. During the initial phase, there is a uniform decrease in the density of Y10B label. In the second phase, some NM neurons recover the capacity to bind the Y10B antibody while others remain unlabeled. During this second phase, NM neurons putatively destined to die, based on their failure to synthesize protein, are unlabeled by the Y10B antibody. New gene expression is not necessary to initiate the change in ribosomal immunoreactivity that leads deafferented NM neurons toward cell death. Blocking cytoplasmic protein synthesis with cycloheximide had no effect on the biphasic change in Y10B labeling of afferent-deprived NM neurons. Treating chicks with chloramphenicol, however, prevented the recovery of Y10B immunoreactivity in NM neurons during the second phase of the response to afferent deprivation.
Effects of excitotoxic lesions of the septum and vertical limb nucleus of the diagonal band of Broca on conditional visual discrimination: relationship between performance and choline acetyltransferase activity in the cingulate cortex
Authors: Marston HM , West HL , Wilkinson LS , Everitt BJ , Robbins TW
Published: April 2018

Four experiments examined the role of the cholinergic projections from the septum and vertical limb nucleus of the diagonal band of Broca (VDB) in acquisition and performance of a conditional visual discrimination. In experiments 1–3, excitotoxic lesions were made of the septum and VDB in rats using quisqualic acid, which resulted in significant reductions in ChAT activity in the hippocampus and cingulate cortex, but with no effects on cortical monoamines. In experiment 1, there were significant impairments in acquisition of the conditional discrimination, which did not result from motivational impairments. Experiment 2 repeated these results with lesion parameters, which produced variable effects on hippocampal and cingulate ChAT activity. Those rats with reductions in predominantly cingulate ChAT were most impaired in acquisition, but those with predominantly hippocampal reductions were relatively unimpaired. Experiment 3 showed that quisquate-induced lesions of the VDB, but not of the more caudal VDB and horizontal limb nucleus of the diagonal band, produced deficits, and a model incorporating the results of experiments 1–3 showed a highly significant correlation between errors of commission and cingulate cortical ChAT activity (r = -0.82, p < 0.001). Experiment 4 used the excitotoxin AMPA to lesion the VDB in rats pretrained on a modified form of the conditional discrimination task. In one subgroup of rats this excitotoxin produced profound and regionally selective reductions in ChAT activity. This subgroup was also impaired in relearning the discrimination to criterion. Again, there was a significant inverse relationship between the number of errors of commission made in relearning the discrimination and cingulate ChAT activity (r = -0.94, p < 0.001). These experiments suggest that excitotoxic lesions of the septum/VDB produce deficits in conditional discrimination learning and performance, and that the integrity of the projection to the cingulate cortex is more crucial than that to the hippocampus in this effect. Moreover, there is a close relationship between discrimination performance and cholinergic function in the cingulate cortex. In conjunction with other results, these data suggest that different aspects of cognition and memory are modulated by cholinergic activity in different cortical regions.
Regulation of neurotrophin receptor expression during embryonic and postnatal development
Authors: Escandon E , Soppet D , Rosenthal A , Mendoza-Ramirez JL , Szonyi E , Burton LE , Henderson CE , Parada LF , Nikolics K
Published: April 2018

Members of the NGF family of proteins act as neurotrophic agents for defined populations of peripheral and central neurons during embryonic and postnatal development. We have studied the presence of receptors for brain-derived neurotrophic factor (BDNF) and neurotrophin-3 and - 4/5 (NT-3, NT-4/5) by cross-linking radioiodinated neurotrophins to specific cell surface receptors. We have identified neurotrophin receptors representing full-length TrkB and TrkC and their truncated forms (lacking a functional cytoplasmic kinase domain) in neuronal as well as in non-neuronal tissues. During chicken embryonic and early postnatal brain development, expression of full-length TrkB and TrkC proteins preceded the onset of the truncated forms of these receptors. A similar pattern was also observed in mouse embryonic and early postnatal brain. The relative levels of neurotrophin receptors in the basal forebrain and in the hippocampus did not change significantly with age in mice. High levels of receptors for the three neurotrophins were detected in the nigrostriatal system. Full-length TrkB and TrkC receptors were found in chicken and rat embryonic ventral spinal cord, as well as on purified motoneurons. Again, truncated TrkB appeared significantly later than the full-length form on spinal motoneurons. In chicken embryonic retina and optic tectum we detected full-length TrkB and TrkC; however, the optic tectum also expressed large amounts of the truncated form of TrkB. TrkC but not TrkB was detected in chicken embryonic skeletal muscle, suggesting that NT-3 may have a novel function in this tissue. The presence of neurotrophin receptors in a wide variety of embryonic and postnatal tissues underlines the significant role of BDNF, NT-3, and NT-4/5 in embryonic and postnatal development. The regulation of the ratio of full-length versus truncated neurotrophin receptors may play an important role in the development, maturation, and maintenance of various neuronal networks.
Responses in macaque visual area V4 following inactivation of the parvocellular and magnocellular LGN pathways
Authors: Ferrera VP , Nealey TA , Maunsell JH
Published: April 2018

A substantial body of evidence has suggested that signals transmitted through the magnocellular and parvocellular subdivisions of the LGN remain largely segregated in visual cortex. This hypothesis can be tested directly by selectively blocking transmission through either the magnocellular or parvocellular layers with small injections of lidocaine or GABA while recording cortical responses to a visual stimulus. In a previous study, we found that responses in the middle temporal visual area (MT) were almost always greatly reduced by blocks of magnocellular LGN, but that few MT neurons were affected by parvocellular blocks. In the present study, we have examined magnocellular and parvocellular contributions to area V4, which lies at the same level of processing in the cortical hierarchy as does MT and is thought to be a major recipient of parvocellular input. We found that inactivation of parvocellular layers usually resulted in a moderate reduction of visual responses (median reduction, 36%). However, comparable reductions in V4 responses were also seen following magnocellular blocks (median reduction, 47%). Directionally selective responses in V4 were not found to depend specifically on either subdivision. We conclude that area V4, unlike MT, receives strong input from both subdivisions of the LGN. These results suggest that the relationship between the subcortical magnocellular and parvocellular pathways and the parietal and temporal streams of processing in cortex is not one-to-one.
Developmental changes in electrophysiological properties of LGNd neurons during reorganization of retinogeniculate connections
Authors: Ramoa AS , McCormick DA
Published: April 2018

Changes in electrophysiological properties of neurons in the ferret dorsal LGN (LGNd) were studied during early postnatal life, a critical developmental period when changes occur in morphology, connectivity, and response properties of LGNd neurons. Using the patch-clamp technique to obtain whole-cell recordings from cells maintained as in vitro slices of thalamus, several distinctive properties were observed in the immature LGNd. Relatively low resting membrane potentials were present that became more negative during the first 2 postnatal weeks. In addition, immature neurons exhibited high input resistances that decreased during early postnatal development. At all ages postnatally, neurons were capable of generating a train of Na(+)-dependent action potentials in response to intracellular injection of a depolarizing current pulse. Moreover, immature neurons resembled older cells in that little spike frequency adaptation was present during a train of action potentials. Action potential activity in immature neurons was nevertheless distinctive in several respects: (1) during the first 2–3 postnatal weeks action potentials became shorter in duration and larger in amplitude; (2) during the same period, thresholds for generation of action potentials changed in conjunction with the changes in resting membrane potential, becoming more negative; and (3) plots of frequency versus injected current revealed that thresholds for generation of trains of action potentials were reached with intracellular injection of lower current levels at earlier ages. These findings raise the possibility that relatively weak ionic currents generated at immature synapses have unexpectedly strong effects on the young LGNd neuron.(ABSTRACT TRUNCATED AT 250 WORDS)
A single transmitter regulates gene expression through two separate mechanisms: cholinergic regulation of phenylethanolamine N- methyltransferase mRNA via nicotinic and muscarinic pathways
Authors: Evinger MJ , Ernsberger P , Regunathan S , Joh TH , Reis DJ
Published: April 2018

ACh regulates the gene encoding phenylethanolamine N-methyltransferase (PNMT) in bovine adrenal chromaffin cells. In addition to stimulating catecholamine release from these cells, cholinergic agents elevate transcription of the PNMT gene. Carbachol, which activates both nicotinic and muscarinic receptors, produces 12–19-fold increases in PNMT mRNA and a 22-fold increase in epinephrine release. Selective nicotinic and muscarinic antagonists (hexamethonium and atropine) each partially reduce carbachol-stimulated increases in PNMT mRNA while a combination of both eliminates > 90% of the carbachol response, thus indicating that separable nicotinic and muscarinic components contribute to the cholinergic increase in PNMT mRNA. Muscarine alone produces a dose-dependent increase (mean sixfold) in steady state PNMT mRNA levels and stimulates the rate of transcription fivefold. Only atropine and the m3-m4-selective muscarinic antagonist 4- diphenylacetoxy-4-methyl-piperidine (4-DAMP) reduce the response to muscarine, strongly suggesting that the m4 receptor is crucial for PNMT mRNA activation. In these chromaffin cells, muscarine inhibits adenylate cyclase, antagonist bind with affinities characteristic of m4 receptors, and cDNA hybridization detects only m4 mRNAs (Fernando et al., 1991). Nicotine also induces a dose-dependent increase (mean of 8.5-fold) in PNMT mRNA levels. The importance of voltage-gated Ca2+ channels in the nicotine effect is demonstrated by the stimulatory effects of calcium ionophores on PNMT mRNA levels (two-to fivefold increase) and the ability of the L- and N-type channel blockers nifedipine and omega-conotoxin to decrease the nicotine response (by 60% and 40%, respectively). Nuclear “run-on” assays further reveal that nicotine enhances transcription of the PNMT gene (approximately fourfold). Thus, this study provides the first demonstration that both nicotinic and muscarinic stimulation modify genomic responses of bovine adrenergic chromaffin cells and identifies possible mechanisms.