bluuebunny/crossref_metadata_2025 huggingface dataset:
Epidural analgesia at trial of labor after cesarean (TOLAC): a significant adjunct to successful vaginal birth after cesarean (VBAC)
Authors: Grisaru-Granovsky Sorina , Bas-Lando Maayan , Drukker Lior , Haouzi Fred , Farkash Rivka , Samueloff Arnon , Ioscovich Alexander
Published: April 2018

Introduction:

Epidural analgesia has been considered a risk factor for labor dystocia at trial of labor after cesarean (TOLAC) and uterine rupture. We evaluated the association between exposure to epidural during TOLAC and mode of delivery and maternal-neonatal outcomes.

Materials and methods:

A single center retrospective study of women that consented to TOLAC within a strict protocol between 2006 and 2013. Epidural “users” were compared to “non-users”. Primary outcome was the mode of delivery: repeat in-labor cesarean or vaginal birth after cesarean (VBAC). Secondary outcomes were maternal/neonatal morbidities. Univariate/multivariate analyses for associations between epidural and mode of delivery were adjusted for significant covariates/mediators.

Results:

Of a total of 105,471 births registered, 9464 (9.0%) were eligible for TOLAC; 7149 (75.5%) women consented to TOLAC, among which 4081 (57.1%) had epidural analgesia. The in labor cesarean rate was significantly lower for the epidural “users” 8.7% vs. “non-users” 11.8%, P<0.0001, with a parallel increased rate of instrumental delivery. Uterine rupture rates were comparable: 0.4% and 0.29%, respectively (P=0.31). The adjusted multivariate model showed that epidural “users” were more likely to experience a VBAC, odds ratio (OR) 4.58 [3.67; 5.70]; P<0.0001 with a similar rate of adverse maternal-neonatal outcomes.

Conclusion:

Epidural analgesia at TOLAC may emerge as a safe and significant adjunct for VBAC.
Reliability and Validity of the 6-Minute Step Test for Clinical Assessment of Cardiorespiratory Fitness in People at Risk of Cardiovascular Disease
Authors: Giacomantonio Nicholas , Morrison Paul , Rasmussen Roy , MacKay-Lyons Marilyn J.
Published: April 2018

Giacomantonio, N, Morrison, P, Rasmussen, R, and MacKay-Lyons, MJ. Reliability and validity of the 6-minute step test for clinical assessment of cardiorespiratory fitness in people at risk of cardiovascular disease. J Strength Cond Res 34(5): 1376–1382, 2020—The purpose of this study was to determine the test-retest reliability and validity of the 6-minute step test (6MST) as a potential assessment of cardiorespiratory fitness (CRF) of people at risk of cardiovascular disease (CVD). A prospective, cross-sectional, correlational study design was used. A single cohort of 30 adults with 2 or more risk factors for CVD was recruited. Exercise tests were scheduled on 2 days, separated by 1 week. Validity was determined by comparing 6MST results with those obtained in a symptom-limited treadmill test and the 6-minute walk test (6MWT). Main outcome variables were peak heart rate (HRpeak) and peak oxygen consumption (V̇o
2peak) measured during the 6MST, treadmill test, and 6MWT. Test-retest reliability of HRpeak and V̇o
2peak during the 6MST was very strong (intraclass correlation coefficient [ICC], 0.92; 95% confidence interval [CI], 0.83–0.97 and ICC, 0.93; 95% CI, 0.84–0.97, respectively). Correlations were also very strong between 6MST and treadmill test HRpeak (r = 0.81) and between 6MST and treadmill test V̇o
2peak (r = 0.88). Correlations were moderate between 6MST HRpeak and 6MWT steady-state HR (r = 0.57) and strong between 6MST V̇o
2peak and 6MWT steady-state V̇o
2 (r = 0.70). The 6MST seems to be a reliable, valid option for assessing CRF of people at risk of CVD in a broad range of clinical settings. Providing practical, accessible tests will help facilitate the goal of establishing CRF as a clinical vital sign. The next step in the development of the 6MST should be to identify the most appropriate 6MST predictor variables to estimate V̇o
2max.
Low Energy Availability, Plasma Lipids, and Hormonal Profiles of Recreational Athletes
Authors: Black Katherine , Slater Joanne , Brown Rachel C. , Cooke Rebecca
Published: April 2018

Black, K, Slater, J, Brown, RC, and Cooke, R. Low energy availability, plasma lipids, and hormonal profiles of recreational athletes. J Strength Cond Res 32(10): 2816–2824, 2018—It has been postulated that low energy availability (LEA) impacts bone health, hormonal concentrations, and cardiovascular function. This study describes the lipid levels, hormonal profiles, and nutrient intakes of recreationally active adults at risk of LEA compared with those not at risk. Thirty-eight women who meet or exceed the New Zealand guidelines for physical activity participated. Each participant completed an online questionnaire including the Low Energy Availability in Females questionnaire (LEAF-Q), demographic questions, and daily exercise to determine energy expenditure. Participants also provided a weighed 3-day diet record, a blood sample analyzed for total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, and cortisol, and a saliva sample analyzed for testosterone. Body composition was assessed using bioelectrical impedance. Those classed as at risk of LEA according to the LEAF-Q showed very likely lower energy availability (at risk: mean, 36.3 [95% confidence interval, 30.8–41.7] kcal·kg−1·FFMd−1 vs. not at risk: mean, 47.5 [95% CI, 39.5–55.4] kcal·kg−1·FFMd−1) and lower calcium intakes (mean, 847 [95% CI, 695–998] mg, vs. mean, 1488 [95% CI, 690–2,286] mg). Those at risk also had a likely small lower T3 concentration of 1.78 (SD: 0.36) nmol·L−1 compared with 2.01 (SD: 0.53) nmol·L−1 for those not at risk. These data suggest that recreationally active female subjects classed as at risk of LEA according to the LEAF-Q also have lower energy availability as determined by diet records and exercise diaries. The results also suggests that those at risk of LEA have reductions in T3, and their low energy intake, in addition to a low calcium intake, could put them at an increased risk of poor bone health.
Intracranial Electrophysiology Reveals Reproducible Intrinsic Functional Connectivity within Human Brain Networks
Authors: Kucyi Aaron , Schrouff Jessica , Bickel Stephan , Foster Brett L. , Shine James M. , Parvizi Josef
Published: April 2018

Evidence for intrinsic functional connectivity (FC) within the human brain is largely from neuroimaging studies of hemodynamic activity. Data are lacking from anatomically precise electrophysiological recordings in the most widely studied nodes of human brain networks. Here we used a combination of fMRI and electrocorticography (ECoG) in five human neurosurgical patients with electrodes in the canonical “default” (medial prefrontal and posteromedial cortex), “dorsal attention” (frontal eye fields and superior parietal lobule), and “frontoparietal control” (inferior parietal lobule and dorsolateral prefrontal cortex) networks. In this unique cohort, simultaneous intracranial recordings within these networks were anatomically matched across different individuals. Within each network and for each individual, we found a positive, and reproducible, spatial correlation for FC measures obtained from resting-state fMRI and separately recorded ECoG in the same brains. This relationship was reliably identified for electrophysiological FC based on slow (<1 Hz) fluctuations of high-frequency broadband (70–170 Hz) power, both during wakeful rest and sleep. A similar FC organization was often recovered when using lower-frequency (1–70 Hz) power, but anatomical specificity and consistency were greatest for the high-frequency broadband range. An interfrequency comparison of fluctuations in FC revealed that high and low-frequency ranges often temporally diverged from one another, suggesting that multiple neurophysiological sources may underlie variations in FC. Together, our work offers a generalizable electrophysiological basis for intrinsic FC and its dynamics across individuals, brain networks, and behavioral states.

SIGNIFICANCE STATEMENTThe study of human brain networks during wakeful “rest”, largely with fMRI, is now a major focus in both cognitive and clinical neuroscience. However, little is known about the neurophysiology of these networks and their dynamics. We studied neural activity during wakeful rest and sleep within neurosurgical patients with directly implanted electrodes. We found that network activity patterns showed striking similarities between fMRI and direct recordings in the same brains. With improved resolution of direct recordings, we also found that networks were best characterized with specific activity frequencies and that different frequencies show different profiles of within-network activity over time. Our work clarifies how networks spontaneously organize themselves across individuals, brain networks, and behavioral states.
The Magnitude, But Not the Sign, of MT Single-Trial Spike-Time Correlations Predicts Motion Detection Performance
Authors: Hashemi Alireza , Golzar Ashkan , Smith Jackson E.T. , Cook Erik P.
Published: April 2018

Spike-time correlations capture the short timescale covariance between the activity of neurons on a single trial. These correlations can significantly vary in magnitude and sign from trial to trial, and have been proposed to contribute to information encoding in visual cortex. While monkeys performed a motion-pulse detection task, we examined the behavioral impact of both the magnitude and sign of single-trial spike-time correlations between two nonoverlapping pools of middle temporal (MT) neurons. We applied three single-trial measures of spike-time correlation between our multiunit MT spike trains (Pearson's, absolute value of Pearson's, and mutual information), and examined the degree to which they predicted a subject's performance on a trial-by-trial basis. We found that on each trial, positive and negative spike-time correlations were almost equally likely, and, once the correlational sign was accounted for, all three measures were similarly predictive of behavior. Importantly, just before the behaviorally relevant motion pulse occurred, single-trial spike-time correlations were as predictive of the performance of the animal as single-trial firing rates. While firing rates were positively associated with behavioral outcomes, the presence of either strong positive or negative correlations had a detrimental effect on behavior. These correlations occurred on short timescales, and the strongest positive and negative correlations modulated behavioral performance by ∼9%, compared with trials with no correlations. We suggest a model where spike-time correlations are associated with a common noise source for the two MT pools, which in turn decreases the signal-to-noise ratio of the integrated signals that drive motion detection.

SIGNIFICANCE STATEMENTPrevious work has shown that spike-time correlations occurring on short timescales can affect the encoding of visual inputs. Although spike-time correlations significantly vary in both magnitude and sign across trials, their impact on trial-by-trial behavior is not fully understood. Using neural recordings from area MT (middle temporal) in monkeys performing a motion-detection task using a brief stimulus, we found that both positive and negative spike-time correlations predicted behavioral responses as well as firing rate on a trial-by-trial basis. We propose that strong positive and negative spike-time correlations decreased behavioral performance by reducing the signal-to-noise ratio of integrated MT neural signals.
Synaptic interactions between GABA-immunoreactive profiles and the terminals of functionally defined myelinated nociceptors in the monkey and cat spinal cord
Authors: Alvarez FJ , Kavookjian AM , Light AR
Published: April 2018

This study analyzes the synaptic interactions between the central terminals of A delta high threshold mechanoreceptors (A delta HTMs) and GABA-immunoreactive profiles. A delta HTM primary afferents from three monkeys and one cat were electrophysiologically identified and intracellularly labeled with HRP, and their terminal arborizations in laminae I and II of the sacrocaudal spinal cord were studied at the ultrastructural level. GABA-immunoreactive profiles in relation to A delta HTM terminals were demonstrated using postembedding colloidal gold techniques. Monkey A delta HTM terminals (n = 131) usually constituted the central element of synaptic glomeruli; they established large asymmetric synaptic contacts with 1-13 dendrites (modal value 2- 4) and were surrounded by 0-6 peripheral axon terminals (modal value 2- 3). The large majority (around 85%) of the peripheral axon terminals were GABA immunoreactive. They were found presynaptic to the A delta HTM terminal and/or to dendrites postsynaptic to the primary afferent terminal. Furthermore, all peripheral axon terminals found presynaptic to the A delta HTM terminals showed GABA immunoreactivity. Within a single A delta HTM fiber, this synaptic arrangement was found in 20-60% of its boutons. In addition, 28% of the postsynaptic dendritic profiles displayed weak GABA immunoreactivity. Some of them contained vesicles; however, only in a few cases did we observe synapses between a GABA- immunoreactive vesicle-containing dendrite and a dendritic profile postsynaptic to an A delta HTM terminal. Similar synaptology and interactions with GABA-immunoreactive profiles were displayed by the terminals of the single cat A delta HTM fiber studied. Our data support the hypothesis that GABA-containing neurons use both presynaptic and/or postsynaptic mechanisms to exert a powerful control, presumably inhibitory, over the transmission of nociceptive information between A delta HTM afferents and second-order neurons in monkey and cat spinal cord. Our results also imply that GABA may be released within the synaptic glomeruli formed by A delta HTM terminals either by local dendrites or by axon terminals. We discuss the possibility that these GABAergic synapses can be driven by inputs from both primary afferents and/or descending systems to modulate the transmission of nociceptive sensory information.
The role of NMDA and non-NMDA excitatory amino acid receptors in the excitation of primate spinothalamic tract neurons by mechanical, chemical, thermal, and electrical stimuli
Authors: Dougherty PM , Palecek J , Paleckova V , Sorkin LS , Willis WD
Published: April 2018

The role of excitatory amino acids (EAAs) in the excitation of monkey spinothalamic tract (STT) neurons following activation of cutaneous primary afferent fibers by noxious and non-noxious stimuli was investigated. The responses of STT neurons to either NMDA or non-NMDA EAA ligands were blocked by infusion of specific antagonists through a microdialysis fiber into the region surrounding the cells. Our results show that blockade of non-NMDA receptors results in a nearly complete elimination of the responses of STT neurons to all stimuli. Blockade of NMDA receptors results in an attenuation of the responses to noxious stimuli but, in addition, prevents the development of the sensitization of STT neurons that is often observed after intradermal injection of capsaicin. These observations further support a role of EAAs in the transmission of sensory information from primary afferent fibers to dorsal horn neurons and a role for NMDA receptors in the generation of hyperalgesia.
Polysialic acid is required for optimal growth of axons on a neuronal substrate
Authors: Zhang H , Miller RH , Rutishauser U
Published: April 2018

Formation of axonal pathways involves a variety of molecules that influence cell-cell interactions. The polysialic acid (PSA) moiety of the neural cell adhesion molecule (NCAM) is present on neuronal surfaces during process outgrowth. Our studies reveal that the removal of PSA causes a decrease in the rate of elongation of retinal cell processes on a substrate of neuronal membranes derived from chick tectum. This effect was partially reversed by antibodies against the L1 adhesion molecule, but not by antibodies against NCAM, N-cadherin, or beta 1-integrins. This predominant effect of PSA on L1 was also observed in short-term, cell-cell adhesion assays, suggesting that PSA promotes optimal outgrowth on neuronal substrates by limiting the consequences of L1-mediated adhesion.
Robust enkephalin innervation of the locus coeruleus from the rostral medulla
Authors: Drolet G , Van Bockstaele EJ , Aston-Jones G
Published: April 2018

Substantial evidence indicates that the noradrenergic nucleus locus coeruleus (LC) is a key target of endogenous opioid neurons, and an important structure in mediating opiate effects. However, the detailed distribution of opioid fibers and terminals in the LC, and the sources of its opioid innervation are unknown. In the present study, the enkephalin innervation of the LC was investigated in the rat using an antibody directed against the extended enkephalin peptide Met- enkephalin-Arg6-Gly7-Leu8 (ENK), which is derived exclusively from the enkephalin precursor proenkephalin A. An antibody directed against tyrosine hydroxylase (TH), the synthetic enzyme for catecholaminergic neurons, was also applied to the same tissue sections to delineate LC neurons and their dendrites. Enkephalin fibers in the LC were dense and highly varicose. In horizontal sections, ENK-like-immunoreactive (ENK- ir) fibers of considerable length coursed throughout the rostrocaudal orientation of the LC proper, whereas in frontal sections ENK-ir processes appeared punctate, suggesting a rostrocaudal orientation. Dense ENK-ir fibers were also identified in the rostromedial and caudal juxtaependymal pericoerulear regions where extranuclear dendrites of LC neurons are extensive. As previously reported, there were no ENK-ir neurons in the LC nucleus proper, but such cells were present in neighboring structures such as the parabrachial, sphenoid, and Barrington's nuclei as well as in the central gray and in the subcoeruleus area. ENK-ir neurons were also present in nuclei of the rostral medulla reported to be major afferents of the LC, the nucleus prepositus hypoglossi (PrH), and the nucleus paragigantocellularis (PGi). In the dorsomedial medulla, numerous ENK-ir neurons were identified in the medial aspect of the PrH and along the medial longitudinal fasciculus in the perifascicular reticular formation. In the ventrolateral medulla, ENK-ir neurons were distributed in a conical caudorostral column throughout the PGi. Retrograde transport of a WGA- colloidal gold conjugate (WGA-apoHRP-Au) from LC, combined with immunohistochemistry for ENK in the same tissue sections, revealed that LC afferents in the PGi and PrH were interdigitated with ENK-ir neurons. Furthermore, an unexpectedly high incidence of doubly labeled neurons were identified in both PGi and PrH. Overall, 57% and 56% of the LC-projecting neurons in PGi and PrH, respectively, were also immunoreactive for ENK, suggesting that enkephalinergic neurons of PGi and PrH are major afferents to noradrenergic LC neurons.
Sulforhodamine labeling of neural circuits engaged in motor pattern generation in the in vitro turtle brainstem-cerebellum
Authors: Keifer J , Vyas D , Houk JC
Published: April 2018

A fluorescent molecular probe was used in combination with a novel in vitro preparation to study spatial patterns of neural activity associated with motor pattern generation. The in vitro brainstem- cerebellum preparation takes advantage of the turtles's unusual resistance to anoxia to preserve the entire neural network that connects the cerebellum, red nucleus, and reticular formation. This preparation was bathed in a 0.01% solution of sulforhodamine while it was activated unilaterally by electrical stimulation of the dorsal quadrant of the spinal cord for 1 hr. Sulforhodamine is a small, sulfonated, highly charged fluorescent molecule that is taken up by endocytosis. To examine its distribution in the cerebellum and brainstem, coronal sections were prepared and viewed under epifluorescence illumination. Distinctive spatial patterns of labeling were associated with unilateral electrical stimulation of the in vitro network, suggesting that dye uptake was activity dependent. Blockade of uptake with altered magnesium and calcium concentrations indicated that single spike discharge evoked ortho- or antidromically was insufficient to induce dye uptake. Instead, sulforhodamine staining correlated with the presence of burst discharge that was recorded extracellularly from the red nucleus. Blockade of burst discharge with excitatory amino acid receptor antagonists prevented dye uptake in the red nucleus, the lateral cerebellar nucleus, and other structures that are known to be interconnected by recurrent anatomical pathways. These results suggest that sulforhodamine is internalized by intensely active neurons. The spatial distributions of label support the hypothesis that burst discharges in the turtle red nucleus are mediated by excitatory amino acid neurotransmitters and sustained by recurrent excitation in cerebellorubral synaptic pathways. Positive feedback in these recurrent pathways may provide an important driving force for the generation of motor programs that control limb movements.
Peptides and the primary afferent nociceptor
Authors: Levine JD , Fields HL , Basbaum AI
Published: April 2018

An expanding knowledge of neuropeptides and their function has led to a profound change in our view of how the PAN contributes to pain. In addition to their expected direct action on postsynaptic cells in the dorsal horn, neuropeptides can modify transmitter release from nearby terminals of other PANs and/or diffuse to act on dorsal horn neurons at a considerable distance from their site of release (Fig. 2). Contrary to early expectations and despite the evidence that several neuropeptides excite central nociceptive neurons, there is no clear correspondence between neuropeptide content and physiologically defined classes of small-diameter primary afferents. There is, however, a tendency for populations of afferents innervating different organs to differ consistently in their peptide content. In fact, the peptide content of primary afferents is, in part, determined by specific factors in the tissues that they innervate. Furthermore, peptide content can change dramatically in response to certain prolonged stimuli or nerve damage. The lack of correspondence of peptide content and physiological response pattern, the plasticity of peptide content, its tissue specificity, and the possibility for action at a distance from the site of their release from central PAN terminals strongly suggest that PAN peptides have functions that are fundamentally different from those of the short-range actions of amino acid neurotransmitters that are also found in the PAN. Finally, nowhere is the plasticity of function of the PAN more evident than at its peripheral terminals. Long-term changes are produced in these terminals by a host of peptides that derive from a variety of cell types. The complexity of this transduction process is augmented by the activity- induced release of peripherally active neuropeptides from the PAN itself. In addition to the variety of fundamental neurobiological issues that recent studies of PANs have raised, they have also generated a great deal of clinical interest, in view of the role of the PAN in inflammation and its accessibility for study and for therapeutic intervention.
Hyperactivity and sensitization to psychostimulants following cholera toxin infusion into the nucleus accumbens
Authors: Cunningham ST , Kelley AE
Published: April 2018

Although manipulation of second messenger systems is widespread in cell biology, there are few experiments examining the consequences of such manipulation on behavior. In three separate experiments, we extended earlier work by Miller and Kelly (1975) that examined the behavioral effects of microinfusion of cholera toxin (CTX) into the nucleus accumbens (N. Acc.) in rats. CTX is a bacterial toxin that ADP- ribosylates the Gs transducer protein and stimulates production of cAMP. For Experiment I, three groups of rats received either saline or CTX (50 or 500 ng/microliter) into the N. Acc. Locomotor activity was measured for 4 hr following a single CTX infusion and subsequently for 4 hr on 6 consecutive days. No acute effects on motor activity were observed. However, the 500 ng dose of CTX induced long-lasting hyperactivity that was apparent 24 hr later and that lasted 4 d. A smaller but significant hypermotility occurred on days 4 and 5 following infusion of the 50 ng dose. Site specificity of this effect was investigated in Experiment II by infusion of CTX (250 ng/microliter) into either the N. Acc. or the posterior dorsal striatum (PDS). CTX treatment of the PDS had no behavioral effects while the long-lasting hyperactivity following treatment of the N. Acc. was replicated. In Experiment III the effect of intra-accumbens pretreatment with saline or CTX (10 ng/microliter) on d-amphetamine (0.5 mg/kg, i.p.)- and cocaine (7 mg/kg, i.p.)-induced motor activity was investigated.(ABSTRACT TRUNCATED AT 250 WORDS)
Primary structure, neural-specific expression, and dendritic location of human BC200 RNA
Authors: Tiedge H , Chen W , Brosius J
Published: April 2018

Primate BC200 RNA is a 200-nucleotide-long, nontranslatable RNA that is prevalently expressed in the nervous system. We have determined the primary structure of human BC200 RNA, using cDNA cloning and PCR techniques. BC200 RNA can be subdivided into three structural domains. The 5′ region is homologous to Alu repetitive elements that are found in high copy numbers in primate genomes. The central part of BC200 RNA is characterized by a high percentage of A-residues, with a few interspersed other nucleotides. The 3′ sequence is unique to BC200 RNA and shows no apparent similarity with known human DNA sequences. Sequence similarity with rodent BC1 RNA is limited to several short elements, and BC1/BC200 sequence comparisons indicate that the two genes have evolved via separate phylogenetic routes. Probes directed against the 3′ unique part of BC200 RNA detected a single band corresponding to approximately 200 nucleotides on RNA blots. This band was identified only with RNA isolated from human brain, not with RNA from non-neural organs such as lung or kidney. In situ hybridization to selected areas of the human nervous system showed that BC200 RNA is expressed by a subpopulation of neurons that is analogous to the BC1 RNA-expressing subset of neurons in the corresponding areas of the rat nervous system. Moreover, like rat BC1 RNA, human BC200 RNA was localized to dendrite-rich neuropil areas, for example, in the inner plexiform layer of the retina. These results indicate that BC1 RNA and BC200 RNA, although of different evolutionary pedigree, may play analogous functional roles, in rodents and primates, respectively, in somatodendritic domains of nerve cells.
Transplants of immunologically isolated xenogeneic chromaffin cells provide a long-term source of pain-reducing neuroactive substances
Authors: Sagen J , Wang H , Tresco PA , Aebischer P
Published: April 2018

Adrenal medullary chromaffin cells are a potential source of neuroactive substances for transplantation into the CNS to alleviate neurochemical deficits. In particular, work in our laboratory has suggested that adrenal medullary transplants in the spinal subarachnoid space can alleviate pain by providing sustained local delivery of catecholamines and opioid peptides. One of the major limitations for clinical application of neural transplantation is the availability of donor material in sufficient quantities. This limitation may be overcome by the use of xenogeneic donors if long-term graft rejection can be prevented. The purpose of this study was to assess whether xenogeneic chromaffin cells immunologically isolated by semipermeable membranes could survive and continue to reduce pain when transplanted into the CNS. Isolated bovine chromaffin cells were encapsulated by semipermeable polymer membranes and implanted into the rat spinal subarachnoid space. Pain sensitivity was assessed at several intervals up to 3 months following implantation. Results indicated that encapsulated bovine chromaffin cell implants, but not empty control capsules, could repeatedly reduce pain sensitivity with nicotine stimulation for the duration of the study. This response was dose related, indicating that pharmacologic integrity of the transplanted chromaffin cells is retained. The analgesia induced by encapsulated chromaffin cell implants could be attenuated by the opiate antagonist naloxone and the alpha-adrenergic antagonist phentolamine, suggesting the involvement of both opioid peptides and catecholamines in mediating this response. In addition, in vitro neurochemical studies of recultured capsules revealed sustained release of Met-enkephalin and catecholamines from encapsulated cells 3 months following implantation into the spinal subarachnoid space.(ABSTRACT TRUNCATED AT 250 WORDS)
Surface and cytoskeletal markers of rostrocaudal position in the mammalian nervous system
Authors: Kaprielian Z , Patterson PH
Published: April 2018

To identify cell surface molecules that define position in the mammalian nervous system, we previously characterized the binding of two monoclonal antibodies, ROCA1 and ROCA2, to adult rat sympathetic ganglia and intercostal nerves. The binding of ROCA1 is highest in rostral ganglia and nerves and declines in a graded manner in the caudal segments. ROCA2 labels the same cells in ganglia and nerves as ROCA1, but not in a position-selective manner. We now show by immunoblot analysis that ROCA1 recognizes two antigens in membrane/cytoskeletal fractions of peripheral nerves and ganglia: (1) a Triton X-100-insoluble, 60 kDa protein and (2) a Triton x-100- insoluble, 26 kDa protein. The 60 kDa protein is expressed at higher levels in rostral than in caudal intercostal nerves, and is identified as the intermediate filament protein peripherin. In contrast, it is the ROCA1 epitope on the 26 kDa protein, and not the protein itself, that is preferentially visualized immunohistochemically in rostral nerves and ganglia. We suggest that the ROCA1 epitope on the 26 kDa protein is masked in sections of caudal nerves and ganglia. Amino acid sequence data obtained from the affinity-purified 26 kDa protein indicate significant homology with human CD9, a cell surface protein implicated in intercellular signaling in hematopoietic cells. These results suggest that intermediate filament gene expression and epitope masking on the cell surface may be involved in functions related to position in the nervous system.
C-fos expression in the pons and medulla of the cat during carbachol- induced active sleep
Authors: Yamuy J , Mancillas JR , Morales FR , Chase MH
Published: April 2018

Microinjection of carbachol into the rostral pontine tegmentum of the cat induces a state that is comparable to naturally occurring active (REM, rapid eye movement) sleep. We sought to determine, during this pharmacologically induced behavioral state, which we refer to as active sleep-carbachol, the distribution of activated neuron within the pons and medulla using c-fos immunocytochemistry as a functional marker. Compared with control cats, which were injected with saline, active sleep-carbachol cats exhibited higher numbers of c-fos-expressing neurons in (1) the medial and portions of the lateral reticular formation of the pons and medulla, (2) nuclei in the dorsolateral rostral pons, (3) various raphe nuclei, including the dorsal, central superior, magnus, pallidus, and obscurus, (4) the medial and lateral vestibular, prepositus hypoglossi, and intercalatus nuclei, and (5) the abducens nuclei. On the other hand, the mean number of c-fos-expressing neurons found in the masseter, facial, and hypoglossal nuclei was lower in carbachol-injected than in control cats. The data indicate that c- fos expression can be employed as a marker of state-dependent neuronal activity. The specific sites in which there were greater numbers of c- fos-expressing neurons during active sleep-carbachol are discussed in relation to the state of active sleep, as well as the functional role that these sites play in generating the various physiological patterns of activity that occur during this state.
Postsynaptic calcium, but not cumulative depolarization, is necessary for the induction of associative plasticity in Hermissenda
Authors: Matzel LD , Rogers RF
Published: April 2018

The neuronal modifications that underlie associative memory in Hermissenda have their origins in a synaptic interaction between the visual and vestibular systems, and can be mimicked by contiguous in vitro stimulation of these converging pathways. At the offset of vestibular stimulation (i.e., hair cell activity), the B photoreceptors are briefly released from synaptic inhibition resulting in a slight depolarization (2–4 mV). If contiguous pairings of light-induced depolarization and presynaptic vestibular activity occur in close temporal succession, this depolarization “accumulates” and has been hypothesized to culminate in a sustained rise in intracellular Ca2+ and a resultant Ca(2+)-mediated phosphorylation of K+ channels as well as an associated increase in input resistance. Here we demonstrate that this cumulative depolarization is neither necessary nor sufficient for the biophysical modifications of the B cell membrane indicative of memory formation. Consistent with several recent reports of one-trial learning in Hermissenda, one pairing of light with mechanical stimulation of the vestibular hair cells resulted in a rise in neuronal input resistance across the B cell membrane that was attenuated by a prepairing iontophoretic injection of the Ca2+ chelator EGTA (25 mM), indicating that this potentiation was Ca2+ dependent. However, the use of a single pairing negates the possibility of an accumulation of depolarization across trials. In a subsequent experiment, B photoreceptors underwent a cumulative depolarization, and a coincident rise in input resistance, during multiple pairings of light and hair cell stimulation. However, if the B photoreceptor was voltage clamped at its initial resting potential before and after each pairing, thus eliminating the cumulative depolarization, the rise in resistance not only persisted, but was enhanced. Moreover, if unpaired light presentations were followed by a current-induced depolarization (to mimic cumulative depolarization), no increase in input resistance was detected. To assess directly the effect of a cumulative depolarization on the voltage-dependent Ca2+ current, an analysis of the inward current on the B cell soma membrane was conducted. It was determined that (1) the inward current may undergo a partial inactivation during sustained depolarization, (2) the peak current was depressed during repetitive depolarizations, and (3) the peak current underwent a steady- state inactivation, such that it was reduced when elicited from holding potentials more positive than -60 mV. The analysis of this current suggests that pairings of light and presynaptic activity would reduce voltage-dependent Ca2+ influx when those pairings are conducted at depolarized membrane potentials, such as during cumulative depolarization.(ABSTRACT TRUNCATED AT 400 WORDS)
Intragenic sequences are required for cell type-specific and injury- induced expression of the rat peripherin gene
Authors: Belecky-Adams T , Wight DC , Kopchick JJ , Parysek LM
Published: April 2018

Peripherin is a 57 kDa type III intermediate-filament protein that is thought to play a role in axonogenesis both during development and following nerve injury (Oblinger et al., 1989; Escurat et al., 1990; Gorham et al., 1990; Troy et al., 1990b). We have used transgenic mouse technology to define peripherin gene sequences that are necessary for cell type-specific expression and for the increase in peripherin that occurs in response to axonal injury. Correct temporal and nervous system-specific expression resulted when 5.8 kilobases of peripherin 5′ flanking sequence were linked to a reporter gene, but precise cell type- specific expression was achieved only when intragenic sequences were included. When intragenic sequences were present, peripherin transgenes were expressed in dorsal root ganglion neurons and spinal cord motor neurons and were upregulated in these cells following nerve injury.
Differential expression of hyperpolarization-activated currents reveals distinct classes of visual cortical projection neurons
Authors: Solomon JS , Doyle JF , Burkhalter A , Nerbonne JM
Published: April 2018

Combining in vivo retrograde labeling and in vitro electrophysiological recording techniques, we examined the distributions, densities, and biophysical properties of hyperpolarization-activated inward currents in two types of isolated, identified visual cortical projection neurons, superior colliculus-projecting (SCP) and callosal-projecting (CP) cells. In SCP cells, two kinetically distinct time-dependent hyperpolarization-activated inward current components are present. We have termed these Ih,f and Ih,s to denote the fast and slow components, respectively, of Ih activation. In CP cells, in contrast, Ih,f and Ih,s are differentially expressed. In 59% of the CP cells examined, for example, both Ih,f and Ih,s were present. The properties of the currents are indistinguishable from those recorded from SCP cells, although both Ih,f and Ih,s are expressed at significantly lower densities in this subset of CP cells (as compared to the current densities in SCP cells). Of the remaining 41% of the CP cells studied, 26% were found to express only Ih,s, and 12% of the cells expressed neither Ih,f nor Ih,s. Taken together, these results reveal that the electrical properties of CP visual cortical neurons are considerably more heterogeneous than those of SCP cells. The differential expression of Ih,f and Ih,s is expected to influence the integrated responses of different types of cortical projection neurons to excitatory and inhibitory synaptic inputs.
FMRFamide produces biphasic modulation of the LFS motor neurons in the neural circuit of the siphon withdrawal reflex of Aplysia by activating Na+ and K+ currents
Authors: Belkin KJ , Abrams TW
Published: April 2018

The molluscan neuropeptide FMRFamide has an inhibitory effect on transmitter release from the presynaptic sensory neurons in the neural circuit for the siphon withdrawal reflex. We have explored whether FMRFamide also acts postsynaptically in motor neurons in this circuit, focusing on the LFS motor neurons. FMRFamide typically produces a biphasic response in LFS neurons: a fast excitatory response followed by a prolonged inhibitory response. We have analyzed these postsynaptic actions and compared them with the mechanism of FMRFamide's inhibition of the presynaptic sensory neurons. The transient excitatory effect of FMRFamide, which desensitizes rapidly, is due to activation of a TTX- insensitive, Na(+)-dependent inward current. The late hyperpolarizing phase of the FMRFamide response results from activation of at least two K+ currents. One component of the hyperpolarizing response is active at rest and at more hyperpolarized membrane potentials, and is blocked by 5 mM 4-aminopyridine, suggesting that it differs from the previously described FMRFamide-modulated K+ currents in the presynaptic sensory neurons. In addition, FMRFamide increases a 4-aminopyridine-insensitive K+ current. Presynaptically, FMRFamide increases K+ conductance, acting via release of arachidonic acid. In the LFS motor neurons, application of arachidonic acid mimicked the prolonged, hyperpolarizing phase of the FMRFamide response; 4-bromophenacyl bromide, an inhibitor of phospholipase A2, selectively blocked this component of the FMRFamide response. Thus, FMRFamide may act in parallel pre- and post- synaptically to inhibit the output of the siphon withdrawal reflex circuit, producing this inhibitory effect via the same second messenger in the sensory neurons and motor neurons, though a number of the K+ currents modulated in these two types of neurons are different.
Single channel characterization of multiple types of potassium channels in demyelinated Xenopus axons
Authors: Wu JV , Rubinstein CT , Shrager P
Published: April 2018

Single channel currents in internodes of demyelinated Xenopus axons were measured with the gigaseal patch-clamp technique. Demyelination induced by injected lysolecithin allows the entire internodal axolemma to be accessible to a patch electrode. Four classes of K+ channels in this region were characterized. A Ca(2+)-activated K+ channel [K(Ca)] with a single channel conductance of 235 pS was found. In the presence of 10(-3), 10(-4), 10(-5), and 10(-6) M intracellular free [Ca2+]i, the half-activation voltages are -24.1, -20.8, 30.2, and 111 mV, and the voltage sensitivities are 18.3, 17.2, 23.7, and 21 mV per e-fold change in open probability, respectively. The half-activation Ca2+ concentration at 40 mV is 10(-5) M and the Hill coefficient of Ca2+ binding is 1.7. The K(Ca) channels were sometimes found in clusters, three to six channels in a patch. A 125 pS ATP-sensitive K+ channel was inhibited by the internal application of 2 mM ATP. Its activation was voltage independent. This channel may be important in the regulation of resting potential. A background K+ channel exhibited outwardly rectifying unitary current (176 pS) in symmetrical 115 mM KCl solutions but the ensemble-averaged I-V curve was ohmic. The voltage dependence is very weak, 220 mV per e-fold change in open probability. The nearly symmetrical macroscopic I-V curve of the background channel suggests a role in maintaining the axonal resting potential. A 28 pS delayed- rectifier K+ channel is found to be blocked internally by 2 mM 4- aminopyridine and by 10 mM tetraethylammonium. The half-activation voltage is -41 mV and the voltage sensitivity is 8 mV per e-fold change in open probability.
PKA-dependent regulation of mKv1.1, a mouse Shaker-like potassium channel gene, when stably expressed in CHO cells
Authors: Bosma MM , Allen ML , Martin TM , Tempel BL
Published: April 2018

Potassium (K) channels are important regulators of cellular physiology and can themselves be modulated by phosphorylation. We have investigated the potential protein kinase A (PKA) regulation of mKv1.1, a mouse Shaker-like K channel gene, when it is expressed in stably transfected Chinese hamster ovary (CHO) cell lines. Whole-cell patch- clamp records show that expression of mKv1.1 gives rise to a rapidly activating, sustained K+ current, referred to classically as a delayed rectifier-type current. In order to study the effects of PKA, we compared cell lines transfected with mKv1.1 alone with lines cotransfected with both mKv1.1 and a plasmid encoding a dominant negative mutation in the regulatory subunit of PKA. These mutant regulatory subunits bind to endogenous catalytic subunits of PKA but do not respond to cAMP, thereby causing a chronic reduction in the basal PKA activity in these cells. We found that mKv1.1 current kinetics are unaltered but current density is 3.4-fold higher in the cell lines expressing mutant regulatory subunit than in lines expressing only mKv1.1. RNase protection assays indicate that levels of the specific RNA for mKv1.1 are increased almost twofold in the lines expressing mutant regulatory subunit over the lines expressing mKv1.1 only. Further, the levels of mKv1.1 protein, assayed using an mKv1.1 channel- specific antibody, are increased by almost a factor of 3 between the two types of cell lines. These results suggest that PKA can regulate mKv1.1 channel expression by changing steady-state levels of RNA and by other posttranscriptional mechanisms.
Effects on visual recognition of combined and separate ablations of the entorhinal and perirhinal cortex in rhesus monkeys
Authors: Meunier M , Bachevalier J , Mishkin M , Murray EA
Published: April 2018

Performance on visual delayed nonmatching-to-sample was assessed in rhesus monkeys with combined and separate ablations of the perirhinal and entorhinal cortex, as well as in unoperated controls. Combined (i.e., rhinal cortex) lesions yielded a striking impairment on this task, one almost as severe as that seen after combined amygdalohippocampal removals that included some of this subjacent cortex (Mishkin, 1978; Murray and Mishkin, 1984). Ablations of the perirhinal cortex alone produced a deficit nearly as severe as that found after rhinal cortex lesions, whereas ablations of the entorhinal cortex alone produced only a mild deficit. Contrary to the conclusion from an earlier study (Murray and Mishkin, 1986), the present results demonstrate not only that damage limited to the rhinal cortex is sufficient to produce a severe loss in visual recognition, but also that such damage leads to a far greater loss than damage to any other single structure in the medial part of the temporal lobe.
Opioid actions on rat anterior cingulate cortex neurons in vitro
Authors: Tanaka E , North RA
Published: April 2018

Intracellular recordings were made from layer V pyramidal neurons in slices of rat anterior cingulate cortex, using electrodes that contained potassium methylsulfate and biocytin. [Met5]enkephalin (300 nM to 30 microM) reversibly reduced the amplitude of EPSPs evoked by stimulation of the subcortical white matter; the half-maximal concentration was about 800 nM. These EPSPs were blocked by (+/-)-2- amino-5-phosphonovaleric acid and 6-cyano-7-nitroquinoxaline-2,3-dione. [Met5]enkephalin also reduced the amplitude of bicuculline-sensitive IPSPs evoked by stimulation within layer V; the half-maximal concentration was about 60 nM. Both these actions of [Met5]enkephalin were mimicked by the delta-selective agonist DPDPE (Tyr-D-Pen-Gly-Phe-D- Pen) but not by the mu-selective agonist DAMGO (Tyr-D-Ala-Gly-MePhe-Gly- ol); they were blocked by the delta-selective antagonist naltrindole (apparent dissociation constant of about 0.3 nM) but not by the mu- selective antagonist CTOP (D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH2). [Met5]enkephalin did not change the amplitudes of depolarizations evoked by direct application of glutamate or hyperpolarizations evoked by direct application of muscimol (at -55 mV). Fifty percent (22 of 45) of pyramidal cells were hyperpolarized by [Met5]enkephalin; this resulted from an increase in potassium conductance, and it was mimicked by DPDPE and blocked by naltrindole. Five of seven nonpyramidal cells were hyperpolarized by [Met5]enkephalin; this was mimicked by DAMGO and blocked by CTOP.(ABSTRACT TRUNCATED AT 250 WORDS)
Roles of Pax-genes in developing and adult brain as suggested by expression patterns
Authors: Stoykova A , Gruss P
Published: April 2018

We have examined the transcript distribution of six members of the murine paired box-containing gene family (Pax-gene family) in midgestation embryo and adult brain using in situ hybridization analysis. The expression domains of several Pax-genes in the embryo brain were found to correspond with anatomical boundaries that coincide with neuromere landmarks and therefore respect former neuromere territories in the forebrain. The results are consistent with the concept of brain segmentation and suggest a role for Pax-genes in the brain regionalization. In the adult brain the expression of Pax-genes was observed in discreet areas, with a caudal to rostral restriction in the number of the expressed genes. In general the distribution of transcripts along the anterior-posterior axis was similar to that found in midgestation embryo brain, suggesting a role for Pax-genes in the commitment of the precursor cells to different neuronal cell fates and in the maintenance of specific brain cell subtypes. In the cerebellar cortex, the granular cell layer was found to express high levels of the Pax-6 gene, while putative Bergmann glia and cells surrounding the Purkinje cells contained Pax-3 transcripts. The main adult brain structures that expressed distinct Pax-mRNAs were the periglomerular and granular cell layer of olfactory bulb, nuclei of the septum, amygdala, and isthmus, which suggests a role for the Pax-gene family in the specification of the subcortical domains of the evolutionary old limbic system.