bluuebunny/crossref_metadata_2025 huggingface dataset:
Kindling enhances sensitivity of CA3 hippocampal pyramidal cells to NMDA
Authors: Martin D , McNamara JO , Nadler JV
Published: March 2018

Kindling is a form of experimental epileptogenesis in which periodic electrical stimulation of a brain pathway induces a permanently hyperexcitable state. Previous studies suggested that kindling might be explained, at least in part, by an increased sensitivity of brain neurons to NMDA receptor agonists. This possibility was investigated with the use of grease-gap preparations for assaying the depolarizing responses of CA3 and CA1 hippocampal pyramidal cells to amino acid excitants. When studied 1–2 months after the last evoked seizure, CA3 pyramidal cells from kindled rats were five- to sixfold more sensitive to NMDA than CA3 pyramidal cells from controls. A similar, though smaller, effect of stimulation was observed 1 d after the last evoked seizure. The greater potency of NMDA in kindled rats can probably be explained by enhanced expression of NMDA receptors in the presence of a receptor reserve. The stimulation protocol did not alter the ability of Mg2+ to reduce NMDA potency. It also affected neither the response of CA3 pyramidal cells to AMPA [(RS)-alpha-amino-3-hydroxy-5-methyl-4- isoxazolepropionate] nor the response of CA1 pyramidal cells to NMDA or AMPA. In area CA3, the potency of NMDA, but not of AMPA, declined 2.5–4- fold over the 1–2 month experimental period, apparently as a result of increasing age. This age-related loss of sensitivity to NMDA was completely prevented by kindling. These findings suggest that kindling prevents a loss of NMDA receptor function in CA3 pyramidal cells that normally occurs during early adulthood. Such a change could contribute to maintenance of the kindled state.
Cholinergic cell loss and hypertrophy in the medial septal nucleus of the behaviorally characterized aged rhesus monkey
Authors: Stroessner-Johnson HM , Rapp PR , Amaral DG
Published: March 2018

Quantitative studies were conducted to determine the number and size of cholinergic neurons in the medial septal nucleus of four aged (23–25 years old) and four young (10–12 years old) rhesus monkeys. All of the animals had been tested on an extensive battery of learning and memory tasks prior to these experiments. Two of the aged monkeys displayed a pattern of recognition memory deficits that resembled the effects of medial temporal lobe damage. The postmortem anatomical data were analyzed in relation to both the age and behavioral status of the animals. Across all rostrocaudal levels of the medial septal nucleus, there was a 19.3% decrease in the number of cholinergic neurons in the aged monkeys. The loss was regionally selective, however, and ranged from a low of 6.2% rostrally to 40.9% caudally. The degree of cell loss was similar in both memory-impaired and memory-unimpaired aged animals. Morphological analysis also revealed that the mean cross-sectional area of cholinergic neurons was significantly larger in the aged animals. At caudal levels, the increase in average cell size was at least partly due to a disproportionate loss of small to medium size neurons. At rostral levels of the medial septal nucleus, however, where there was minimal cell loss, a clear hypertrophy of cholinergic neurons was evident. Interestingly, the cell hypertrophy observed at these rostral levels was present only in brains from the behaviorally impaired aged monkeys. These findings represent the first morphological demonstration of alterations in cholinergic neurons in the aged nonhuman primate.(ABSTRACT TRUNCATED AT 250 WORDS)
The positional firing properties of medial entorhinal neurons: description and comparison with hippocampal place cells
Authors: Quirk GJ , Muller RU , Kubie JL , Ranck JB
Published: March 2018

Hippocampal place cells in the rat are so named because they fire predominantly within circumscribed regions of the environment. This study describes the positional firing properties of cells afferent to hippocampal place cells, in superficial layers of medial entorhinal cortex (MEC). MEC cells in these layers project to the hippocampus via the perforant path and, along with lateral entorhinal cells, are the sole route by which cortical information reaches the hippocampus. MEC cells were recorded from rats while they retrieved pellets in simple geometric enclosures. The behavioral task as well as procedures for data collection and analysis were the same used in previous studies on hippocampal place cells (e.g., Muller et al., 1987) in order to facilitate the direct comparison between hippocampal and entorhinal cells. The firing patterns of MEC cells show pronounced locational variations reminiscent of hippocampal firing fields, but with a lower signal-to-noise ratio. While noisy, MEC firing patterns are stationary in time as evidenced by their reproducibility, and the improvement in spatial signal with long-duration recordings. Furthermore, MEC firing patterns are not due to variations in the rat's behavior. Taken together, these data show that the positional firing variations in MEC cells are due to the location-specificity of MEC cells. These and additional data lead us to conclude that location-specific information exists prior to the hippocampus. MEC cells are similar to hippocampal place cells in that their firing can be controlled by the rotation of a visual cue (a white card attached to the wall), but is not disrupted by removing the cue. An important difference between hippocampal and entorhinal cells was seen when the shape of the recording chamber was changed. In the transition from a cylinder to an equal-area square of similar appearance, MEC firing patterns topologically transformed (or “stretched”) while those of hippocampal place cells changed to an unpredictable pattern. We conclude that the positional firing of MEC cells is more “sensory bound” than hippocampal cells, and that the ability to discriminate different environments, while present in the hippocampus, is not yet present in its input from MEC.
Properties and rundown of sodium-activated potassium channels in rat olfactory bulb neurons
Authors: Egan TM , Dagan D , Kupper J , Levitan IB
Published: March 2018

We have used single-channel recording techniques to investigate the properties of sodium-activated potassium channels (KNa channels) in cultured rat olfactory bulb neurons, and in large neurons in the mitral cell layer of thin slices of olfactory bulb. Ion channels highly selective for potassium over sodium and chloride, and requiring 10–180 mM internal sodium (Nai) for their activation, were present in approximately 75% of inside-out membrane patches detached from cultured olfactory bulb neurons. Most of these patches contained several KNa channels. KNa channels were seen in cell-attached patches only when Nai was raised by including veratridine in the extracellular medium. Preincubation of the cell in TTX or removal of extracellular sodium prevented this effect of veratridine, confirming that the channels observed under these conditions were indeed KNa channels. Lithium did not substitute for Nai in activating these channels. With 150 mM potassium on both sides of the membrane, KNa channels had a single- channel conductance of 172 pS, and at least two subconducting states were observed in addition to this fully open state. Under these ionic conditions, the channels exhibited linear fully open channel current- voltage curves over the potential range of -100 to 0 mV. At voltages more positive than the potassium equilibrium potential, the single- channel currents exhibited inward rectification as a result of sodium block of outward potassium current. The channels opened in bursts, during which they fluctuated between the fully open and closed states, and the substates. Between bursts they sometimes entered a long-lived inactive state that could last for up to several minutes. In addition, KNa channels in the detached patches exhibited rundown, a progressive irreversible loss in activity, over a time course that varied from less than 1 min to longer than 1 hr. Rundown of KNa channel activity in cell- attached patches (in the presence of veratridine) did not occur, suggesting that some intracellular factor necessary for KNa channel activity is lost when the membrane patch is detached from the cell.
5-hydroxytryptamine1B receptors block the GABAB synaptic potential in rat dopamine neurons
Authors: Johnson SW , Mercuri NB , North RA
Published: March 2018

Intracellular recordings were made from presumed dopamine-containing neurons in slices cut from the midbrain of the rat. Focal electrical stimulation produced a hyperpolarizing synaptic potential that was reduced by 75–95% by the GABAB-receptor antagonist 2-hydroxysaclofen (300 microM). 5-HT (3–100 microM) reduced the amplitude of the GABAB synaptic potential by 20–74%, with a 50% reduction at 10 microM, but did not reduce the amplitude of synaptic potentials mediated by GABAA receptors. 5-HT acted presynaptically because hyperpolarizations produced by exogenously administered GABA (1 mM) in picrotoxin (100 microM) were not affected by 5-HT (30 microM). (+/-)-Cyanopindolol (100 nM), a 5-HT1B antagonist, blocked the effect of 5-HT (10 microM); spiperone (1 microM), which is an antagonist at 5-HT1A and 5-HT2 receptors, had no effect. The amplitude of the GABAB synaptic potential was reduced by the 5-HT1B receptor agonists 1-[3-(trifluoromethyl)- phenyl]-piperazine (300 nM) and 7-trifluoromethyl-4-(4-methyl-1- piperazinyl)-pyrrolo[1,2-a]quinoxaline (1 microM), but not by the 5- HT1A agonist N,N-dipropyl-5-carboxamidotryptamine (1 microM) or the 5- HT2 agonist (+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-amino-propane (10 microM). We conclude that 5-HT activates presynaptic 5-HT1B receptors that inhibit the release of GABA onto GABAB but not GABAA receptors.
L-AP4 inhibits calcium currents and synaptic transmission via a G- protein-coupled glutamate receptor
Authors: Trombley PQ , Westbrook GL
Published: March 2018

The AP4 (2-amino-4-phosphonobutyrate) receptor is a presynaptic glutamate receptor that inhibits transmitter release via an unknown mechanism. We examined the action of L-AP4 on voltage-dependent calcium currents and excitatory synaptic transmission on cultured olfactory bulb neurons using whole-cell voltage-clamp methods. In neurons dialyzed with GTP, L-AP4 inhibited high-threshold calcium currents evoked in barium solutions. The inhibition was irreversible in the presence of GTP-gamma-S and blocked by removing intracellular Mg2+ or by preincubation with pertussis toxin (PTX), consistent with the involvement of a PTX-sensitive G-protein. Dialysis with staurosporine or buffering of intracellular calcium to pCa less than 8 did not block the action of L-AP4, suggesting that protein phosphorylation or release of intracellular calcium stores was not involved in calcium current inhibition under these experimental conditions. PTX also blocked the L- AP4-induced inhibition of monosynaptic EPSPs evoked by intracellular stimulation of cultured mitral cells. These results suggest that the presynaptic AP4 receptor is a G-protein-coupled glutamate receptor, and that inhibition of calcium influx by a membrane-delimited action of a G- protein may account for L-AP4-induced presynaptic inhibition.
Alternate neuromuscular target selection following the loss of single muscle fibers in Drosophila
Authors: Cash S , Chiba A , Keshishian H
Published: March 2018

The Drosophila embryonic and larval body wall consists of a simple array of segmental muscle fibers, innervated in a precise manner by identified neurons. During development motoneurons were forced to find alternate targets following the selective deletion of a single muscle fiber, the pleural internal oblique #5. We used backfills, intracellular dyefills, and immunocytochemistry in embryos and larvae to characterize the normal motoneurons to the fiber. Deleting the fiber using either a genetic or laser lesioning method yielded essentially the same result. In nearly half the cases examined, an ectopically placed neuromuscular projection was found on either of two neighboring muscle fibers, with one favored eight times more than the other. The ectopic projection derived from the nerve branch that normally supplied the deleted muscle fiber 5. Motoneuronal endings on undeleted muscle fibers elsewhere in the body wall had normal morphology. The ectopically placed motor terminals accumulated glutamate in normally sized synaptic boutons, beneath which transmitter sensitivity was localized. The number of boutons and branches at the ectopic endings did not differ significantly from those on intact muscle fiber 5s. Also, the native motoneurons did not alter their arborization sizes in response to a supernumerary ectopically placed contact. While the orientation of the individual ectopically placed branches was variable, the ectopic endings occupied a predictable site on the surrogate muscle fibers. The results suggest that Drosophila motoneurons can project to body wall destinations in the absence of their muscle fiber targets, and that alternate muscle fibers are selected by their proximity. The muscle fibers will support apparently stable and functional supernumerary motor endings on ectopic sites, and these inputs do not significantly influence the behavior of the native motoneurons. The data suggest that Drosophila motoneurons may behave autonomously when making synapses, and that competition does not play a major role in the matching of motoneuron to muscle fiber.
Compartmental distribution of ventral striatal neurons projecting to the mesencephalon in the rat
Authors: Berendse HW , Groenewegen HJ , Lohman AH
Published: March 2018

The ventral striatum is characterized by an intricate neurochemical compartmentation that is reflected in the distribution of most of its afferent fiber systems. In the present study, the compartmental relationships of ventral striatal neurons projecting to the mesencephalon were studied by combining tract tracing with the immunohistochemical localization of leu-enkephalin. Injections of the retrograde tracer cholera toxin subunit B were placed at various sites in the ventral mesencephalon. The anterograde tracer Phaseolus vulgaris leucoagglutinin was injected in single compartments in the rostrolateral part of the nucleus accumbens. The projections from the ventral striatum to the dopaminergic cell groups in the ventral mesencephalon and those to the substantia nigra pars reticulata originate from distinct subpopulations of ventral striatal neurons that respect neurochemically defined compartmental boundaries. In the “shell” of the nucleus accumbens, neurons that project to the dopaminergic cell groups are located outside areas of high cell density and weak enkephalin immunoreactivity (ENK-IR). Rostrolaterally in the “core” of the nucleus accumbens, neurons inside large areas of strong ENK-IR surrounding the anterior commissure project to the dorsomedial part of the substantia nigra pars reticulata, whereas neurons outside these areas innervate the ventral tegmental area and/or the medial part of the substantia nigra pars compacta. By contrast, more caudally in the dorsal part of the nucleus accumbens and in the ventral part of the caudate-putamen, the relationships are reversed: neurons in- or outside small patches of strong ENK-IR project respectively to the pars compacta or the pars reticulata of the substantia nigra. Since the thalamic and cortical afferents of the ventral striatum are compartmentally ordered as well, the present results imply that through the ventral striatal compartments information from disparate combinations of cortical and thalamic sources may be conveyed to distinct mesencephalic targets. The component of the ventral striatomesencephalic system reaching the dopaminergic cell groups A10, A9, and A8 may modulate the dopaminergic input to virtually the entire striatum. The other component can, by way of the pars reticulata of the substantia nigra, participate in nigrothalamic and nigrotectal output pathways of the basal ganglia.
Antibody neutralization of neurite growth inhibitors from oligodendrocytes results in expanded pattern of postnatally sprouting retinocollicular axons
Authors: Kapfhammer JP , Schwab ME , Schneider GE
Published: March 2018

After early postnatal ablation of one superior colliculus together with the ipsilateral eye in Syrian hamsters, retinofugal fibers abnormally cross the tectal midline and innervate the remaining superior colliculus. The fibers of this aberrant decussation are confined mainly to the superficial gray layer, with little ingrowth or termination in the deeper stratum opticum; laterally, most termination is in the superficial part of the superficial gray. Establishment of this abnormal pattern is temporally correlated with the appearance of oligodendrocytes at progressively more superficial locations in the colliculus. Oligodendrocytes express, on their surface, molecules that are inhibitory to neurite growth. This raises the possibility that their differential distribution in the superior colliculus during growth of retinal fibers is causally involved in the generation of the observed termination pattern. We tested this hypothesis by applying the monoclonal antibody IN-1, which neutralizes this inhibitory activity, during the time of postnatal fiber growth and terminal arbor formation. We found that in the presence of IN-1, but not a control antibody, recrossing retinofugal fibers, observed at postnatal day 12, traverse the stratum opticum as well as the superficial gray, with greater depth of termination in superficial gray and stratum opticum. This pattern resembles that of the normal contralateral retinotectal projection. The results indicate that neurite growth inhibitors expressed by oligodendrocytes are responsible for restricting the innervation of a target area in postnatal plasticity.
Effect of intracellular injection of inositol trisphosphate on cytosolic calcium and membrane currents in Aplysia neurons
Authors: Levy S
Published: March 2018

Pacemaker cells of Aplysia californica display a regular bursting that results from a complex interplay of Ca(2+)-mediated conductances and a continuous influx and extrusion of Ca2+. The effect of the second messenger 1,4,5-inositol trisphosphate (InsP3) on intracellular free Ca2+ concentration (Cai) regulation and electrical properties was investigated in identified neurons of the abdominal ganglion (R15, L2- L4, L6). Double-barreled Ca-selective microelectrodes were used to pressure inject InsP3 and measure Cai at the same point. Brief injection of InsP3 resulted in an average increase of Cai of 9.2 +/- 10.0 microM (+/- SE; n = 14) that decayed in about 1 min. The InsP3- induced elevation of Cai increased in a dose-dependent manner and saturated when large amounts of InsP3 were injected. The InsP3-induced Cai increase was the result of mobilization from intracellular stores; Cai could be repeatedly mobilized by InsP3 in cells superfused with 0 Ca artificial seawater for more than 60 min. Following multiple injections of InsP3, there was no evidence of immediate inhibition or facilitation. the spatial nature of the InsP3-induced Cai increase was investigated by moving the double-barreled Ca-selective microelectrode tip in a stepwise manner relative to the membrane surface. The largest InsP3-induced Cai increases were measured in an area 0–80 microns from the membrane surface; some cells had their largest InsP3-induced Cai increase some 120–160 microns away from the membrane. Injection of InsP3 in a bursting neuron induced an immediate train of action potentials followed by membrane hyperpolarization and a decrease in the burst frequency. Injection of InsP3 in voltage-clamped cells induced a biphasic response: a rapid inward current followed by a more prolonged outward current; the temporal overlap of the currents was depth dependent. Injection of InsP3 or Ca2+ from a double-barreled injecting electrode induced currents that were different in waveform and time course, indicating that part of the conductance change induced by InsP3 is direct and not mediated by the mobilized Ca2+. In BAPTA [1,2-bis(2- aminophenoxy)ethane-N,N,N′,N′tetra-acetic acid]-loaded cells, the InsP3- induced inward current was mostly unaffected while the Ca-induced outward current was largely attenuated. The results suggest that InsP3 mobilizes Ca2+ from discrete intracellular compartments and induces distinct changes in membrane currents that seem to be independent of the Cai increase.
Organization of cortical cytoskeleton of cultured chromaffin cells and involvement in secretion as revealed by quick-freeze, deep-etching, and double-label immunoelectron microscopy
Authors: Nakata T , Hirokawa N
Published: March 2018

We have studied the organization of the cytoskeleton in both unstimulated and stimulated cultured chromaffin cells, as well as its relationship with their secretory process by exocytosis. We found the spatial heterogeneity in the intensity of cortical rhodamine-phalloidin staining within a cell. The overall staining pattern or intensity was minimally altered after stimulation, although dopamine-beta-hydroxylase (DBH) antigen, a marker for the chromaffin granule membrane, was exposed preferentially on the plasma membrane areas with lower intensity of rhodamine-phalloidin staining. Using the quick-freeze, deep-etch technique, we found the heterogeneity in the organization of cortical cytoskeletal networks--some regions have actin filament bundles running parallel to the plasma membrane interspersed between granules and the plasma membrane, while others have few actin filaments beneath the plasma membrane before stimulation. Actin filaments were rarely observed in the inner cytoplasm. We did not observe the overall change in its organization after stimulation. Double-label immunogold EM using anti-DBH antibody and anti-actin antibody combined with statistical analysis showed that (1) DBH was exposed on the plasma membrane preferentially where actin was sparse after stimulation (significant at less than 0.1%), although (2) regions having sparse actin were not always the sites for DBH exposure, and (3) the cortical actin zone was sometimes disrupted at the DBH-exposed sites after stimulation. The present data suggested that (1) secretion is related to heterogeneous organization of cortical cytoskeleton after stimulation and (2) massive synchronized reorganization of the cytoskeleton in the whole cell is not necessary for secretion, although small changes of the cytoskeleton might occur under local regulation at each exocytotic site at the moment of the release.
ON- and OFF-pathways form separate neural substrates for motion perception: psychophysical evidence
Authors: Wehrhahn C , Rapf D
Published: March 2018

We have tested the hypothesis that in humans the signals carried by ON- and OFF-pathway respectively are processed for the perception of motion by two distinct physiological substrates. In vertebrates, onset of a bright visual stimulus is signaled to the CNS by ON-center retinal ganglion cells; onset of a dark stimulus is transmitted by OFF-center cells. We chose apparent motion generated by successive presentation of two adjacent lines as a stimulus. Lines presented on a bright background were either darker or brighter than this background. Delayed onset of a pair of bright or dark lines elicits apparent motion at the same time fulfilling the constraint of stimulating either ON- or OFF- center ganglion cells, respectively. We determined the threshold delay needed for subjects to perceive the temporal order of the onset of the two lines for various angular separations. The threshold delay for a pair of bright lines stayed low for separations from 2′ to 7′. The threshold delay for a pair of dark lines was low only within a narrow range of separations centered around 3′. The variation of thresholds with line distance must reflect the existence of a limited processing zone for the perception of motion. The diameter of the processing zone for bright lines is about twice as large as that for dark lines. This suggests that in humans the separation of ON- and OFF-pathways extends to the early stages of motion perception. To test this hypothesis independently, thresholds were determined when a bright and a dark line were presented in succession. This was done for a separation of 3′ where thresholds for a pair of lines with equal contrast are similarly low. Temporal order was perceived correctly only when the delay was at least two to four times as high as the threshold delays found for the equal contrast stimuli.
Elevated expression of type II Na+ channels in hypomyelinated axons of shiverer mouse brain
Authors: Westenbroek RE , Noebels JL , Catterall WA
Published: March 2018

Type I and type III Na+ channels are localized mainly in neuronal cell bodies in mouse brain. Type II channels are preferentially localized in unmyelinated fiber tracts but are not detectable in normally myelinated fibers. In shiverer mice, which lack compact myelin due to a defect in the myelin basic protein gene, elevated expression of type II Na+ channels was observed in the hypomyelinated axons of large-caliber fiber tracts such as the corpus callosum, internal capsule, fimbria, fornix, corpus medullare of the cerebellum, and nigrostriatal pathway by immunocytochemical analysis with subtype-specific antibodies. No difference was observed in the localization of type I and type III Na+ channels between wild-type and shiverer mice. These findings support the hypothesis that type II Na+ channels are preferentially localized in axons of brain neurons and suggest that their density and localization are regulated by myelination. The selective increase in the number of type II channels in hypomyelinated fiber tracts may contribute to the hyperexcitable phenotype of the shiverer mouse.
Reconstruction of action potential development from whole-cell currents of differentiating spinal neurons
Authors: Lockery SR , Spitzer NC
Published: March 2018

The duration and ionic dependence of action potentials are developmentally regulated. Voltage-clamp recordings of amphibian spinal neurons have revealed alterations in five currents. To determine whether the changes in the currents are sufficient to produce the change in action potential duration and ionic dependence, we constructed a Hodgkin-Huxley model of electrical excitability of these neurons. The model shows that the equations describing the voltage- clamped currents of young and mature neurons generate action potentials appropriate in duration and ionic dependence for each developmental stage. Moreover, the observed changes in the currents are quantitatively sufficient to produce the changes in the action potential. The effect of the change in each current is detectable in the model. However, the increase in amplitude of the delayed-rectifier potassium current has the largest effect. The model further shows that changes in action potential duration could be achieved with changes in kinetics rather than amplitude of this current, or with changes in amplitudes of other currents. Thus, although increase in amplitude of the delayed rectifier plays a pivotal role in the maturation of excitability, it is not uniquely positioned to govern the action potential duration.
Corticotropin-releasing factor: long-lasting facilitation of the acoustic startle reflex
Authors: Liang KC , Melia KR , Miserendino MJ , Falls WA , Campeau S , Davis M
Published: March 2018

Intracerebroventricular infusion of corticotropin-releasing factor (CRF) (0.1–1.0 micrograms) produced a pronounced, dose-dependent enhancement of the acoustic startle reflex in rats. This excitatory effect began about 20–30 min after infusion, grew steadily over the 2 hr test period, and lasted at least 6 hr. Higher doses of CRF (10 micrograms) often produced marked facilitation and then inhibition of startle that oscillated repeatedly with a period of 10–20 min. CRF- enhanced startle did not result from an increase in sensitization produced by repetition of the startle stimulus or from a blockade of habituation. Peripheral injections of the autonomic ganglionic blockers hexamethonium (10 mg/kg) or chlorisondamine (3 mg/kg) slightly attenuated the magnitude of CRF-enhanced startle, suggesting a partial role of peripheral sympathetic activation. Intracerebroventricular infusion of the CRF antagonist alpha-helical CRF9–41 (alpha hCRF; 25 or 50 micrograms) blocked CRF-enhanced startle when infused 5 min prior to CRF, indicating a central site of action. CRF-enhanced startle also was reversed when alpha hCRF was given 90 min after infusion of CRF. This suggests that exogenously applied CRF remains in the brain for a very long time after administration or that CRF given exogenously initiates a process that results in a long-lasting activation of endogenous CRF. Because the startle reflex is elevated by both conditioned and unconditioned fear, these data lend further support to the idea that CRF infusion produces a behavioral state that resembles fear or anxiety. Because startle is mediated by a well-defined neural pathway, CRF-enhanced startle may provide a useful behavioral assay to analyze the neural systems upon which exogenous CRF acts to produce its behavioral effects.
Noradrenaline depletion blocks behavioral sparing and alters cortical morphogenesis after neonatal frontal cortex damage in rats
Authors: Kolb B , Sutherland RJ
Published: March 2018

The possibility that cortical noradrenaline (NA) is necessary for sparing of function that occurs after neonatal frontal cortex damage was examined. Spatial localization by rats with frontal cortex damage on postnatal day 7 (P7) was better than that by rats with similar damage sustained as adults. The sparing was abolished in rats depleted of cortical NA by means of neonatal 6-hydroxydopamine (6HDA) administration. The blockade of sparing in the P7 frontal operates was associated with a smaller brain, thinner cortex, and reduced cortical dendritic branching relative to saline-treated P7 frontal operates. NA depletion alone in unoperated rats did not affect spatial learning but did reduce brain size and dendritic branching. Rats with frontal lesions on P4 did not show sparing of spatial localization, and 6HDA administration had no additional behavioral effect. Overall, these data are consistent with the notion that NA has some general function in maintaining some forms of plasticity in posterior cortex.
Microstimulation in visual area MT: effects on direction discrimination performance
Authors: Salzman CD , Murasugi CM , Britten KH , Newsome WT
Published: March 2018

Physiological and behavioral evidence suggests that the activity of direction selective neurons in visual cortex underlies the perception of moving visual stimuli. We tested this hypothesis by measuring the effects of cortical microstimulation on perceptual judgements of motion direction. To accomplish this, rhesus monkeys were trained to discriminate the direction of motion in a near-threshold, stochastic motion display. For each experiment, we positioned a microelectrode in the middle of a cluster of neurons that shared a common preferred direction of motion. The psychophysical task was then adjusted so that the visual display was presented directly over the neurons' receptive field. The monkeys were required to discriminate between motion shown either in the direction preferred by the neurons or in the opposite direction. On half the trials of an experiment, we applied electrical microstimulation while monkeys viewed the motion display. We hypothesized that enhancing the neurons' discharge rate would introduce a directionally specific signal into the cortex and thereby influence the monkeys' choices on the discrimination task. We compared the monkeys' performance on “stimulated” and “nonstimulated” trials in 139 experiments; all trials within an experiment were presented in random order. Statistically significant effects of microstimulation were obtained in 89 experiments. In 86 of the 89 experiments with significant effects (97%), the monkeys indicated that motion was in the neurons' preferred direction more frequently on stimulated trials than on nonstimulated trials. The data demonstrate a functional link between the activity of direction selective neurons and perceptual judgements of motion direction.
Alternatively spliced transcripts of the flp-1 gene encode distinct FMRFamide-like peptides in Caenorhabditis elegans
Authors: Rosoff ML , Burglin TR , Li C
Published: March 2018

We have isolated and characterized several cDNAs and the corresponding genomic region of a gene encoding multiple FMRFamide-like neuropeptides from the nematode Caenorhabditis elegans. The gene, named flp-1, consists of six exons of which four encode FMRFamide-like peptides. The cDNA and genomic sequences revealed that two distinct transcripts are generated by the use of an alternative 3′ splice acceptor site between exons 3 and 4. This alternative splice results in the substitution of AGSDPNFLRFG for one of the copies of SADPNFLRFG found in the other translation product. Based on PCR analysis of RNA from mixed-stage animals, both transcripts are expressed. This gene is the first example of a distinct FMRFamide-like peptide being derived from alternative splicing, suggesting a unique role for the substituted peptide in the animal.
Interaction of the putative essential nutrient pyrroloquinoline quinone with the N-methyl-D-aspartate receptor redox modulatory site
Authors: Aizenman E , Hartnett KA , Zhong C , Gallop PM , Rosenberg PA
Published: March 2018

The putative essential nutrient pyrroloquinoline quinone (PQQ) can efficiently mediate reduction and oxidation reactions in a variety of systems. Therefore, we investigated whether this compound could alter the function of the NMDA receptor via a recently described redox modulatory site. In rat cortical neurons in vitro, 50 microM PQQ could reverse the enhancement of 30 microM NMDA-induced whole-cell ionic currents produced by the reducing agent dithiothreitol (DTT; 2–4 mM). PQQ also depressed native responses in a DTT-reversible fashion. In addition, 50–200 microM PQQ produced a significant degree of neuroprotection in an acute model of NMDA-mediated neurotoxicity in astrocyte-rich cultures of rat cerebral cortex. Under certain conditions, PQQ can lead to the formation of oxygen-derived free radicals, and we have previously observed that these reactive species can oxidize the NMDA receptor. Nevertheless, the enzymatic free radical scavengers superoxide dismutase and catalase (10 micrograms/ml each) did not abolish the actions of PQQ. This observation held true even in astrocyte-poor cortical cultures, where neuronal processes are directly exposed to the extracellular milieu. Therefore, under in vitro conditions in which PQQ is presented without an exogenous electron donor, it appears as if the entire neuroprotective effect of PQQ is attributable to a direct oxidation of the NMDA receptor redox site. These results suggest the possibility of a novel role for PQQ, PQQ-like substances, and quinone-containing proteins in the brain, and may represent a novel therapeutic approach for the amelioration of NMDA receptor-mediated neurotoxic injury.
Single local interneurons in the locust make central synapses with different properties of transmitter release on distinct postsynaptic neurons
Authors: Laurent G , Sivaramakrishnan A
Published: March 2018

Quantal analysis has been applied to the inhibitory synapses made by single spiking local interneurons onto several nonspiking local interneurons (and motorneurons) in the locust CNS. Transmission at these synapses appears to be mediated by GABA. The apparent reversal potential of the IPSP and inhibitory postsynaptic current were -80 to - 85 mV, a value similar to that of the potential evoked by pressure- applied GABA. This reversal potential was 25–30 mV more negative than the resting potential of the nonspiking interneurons in the experimental conditions. The statistical properties of release at these synapses were studied by recording simultaneously from pre- and postsynaptic interneurons with intracellular electrodes. The distribution of postsynaptic potential amplitudes could be described by a simple binomial model, implying uniformity of binomial p (probability of release at a single release site) for each synapse. The mean quantal amplitude was 290 +/- 110 microV, and the mean quantal content m of the IPSPs was 6.25 +/- 2.83. The mean values of binomial n (average size of the releasable pool) and p were 13.11 +/- 2.8 and 0.45 +/- 0.16, respectively. Numerical simulations of statistical experiments were performed to test whether the IPSP amplitude distribution histograms might be misleadingly indicative of quantal release. These simulations showed that such a hypothesis was very unlikely. When a spiking local interneuron was impaled, several of its target interneurons could sometimes be successively sampled. Quantal analysis was then performed with the different IPSPs evoked, in identical conditions, by a same presynaptic interneuron, and the quantal parameters were compared between the synapses. It was found that binomials n and p and their product m generally differed between the synapses made by a given spiking interneuron onto different target neurons. These results show that quantal contents can vary for the many synapses made centrally by one interneuron, and suggest that this variability may arise from differences in release probabilities between the sites associated with different synapses.
A parsimonious description of motoneuron dendritic morphology using computer simulation
Authors: Burke RE , Marks WB , Ulfhake B
Published: March 2018

Most quantitative descriptions of neuronal dendrite morphology involve tabulations of measurements and correlations among them. The present work is an attempt to extract from such data a parsimonious set of parameters that are sufficient to describe the quantitative features of individual and pooled dendrites, including their statistical variability. A relatively simple stochastic (Monte Carlo) model was devised to simulate branching dendritic trees. The necessary parameters were then derived directly from measurements of 64 completely reconstructed dendrites belonging to six gastrocnemius alpha- motoneurons, labeled by intracellular injection of HRP. Comparison of actual and simulated dendrites was used to guide the process of parameter extraction. The model included only two processes, one to generate individual branches given their starting diameters and the second to select starting diameters for the daughter branches produced at dichotomous branching points. The stochastic process for branch generation was controlled by probability functions for branching (Pbr) and for terminating (Ptrm), together with a constant rate of branch taper. All model parameters were fixed by motoneuron measurements except for branch taper rate, which was allowed to vary within limits consistent with observed taper rates in order to generate the appropriate total number of branches. The simplest model (model 1), in which Pbr and Ptrm depended only on local branch diameter, produced simulated dendrites that fit many, but not all, characteristics of actual motoneuron dendrites. Two additional properties produced significant improvements in the fit: (1) a small but significant dependence of daughter diameters on the normalized starting diameter of the parent branch, and (2) a dependence of Pbr and Ptrm on distance from the soma as well as on local branch diameter. The process of developing this model revealed unsuspected relations in the original data that suggest the existence of fundamental mechanisms for morphological control. The final model succinctly describes a large amount of data and will enable quantitative comparisons between the dendritic structures of different types of neurons, regardless of their relative sizes.
Roles of intracellular cAMP and protein kinase A in the actions of dopamine and neurotensin on midbrain dopamine neurons
Authors: Shi WX , Bunney BS
Published: March 2018

The role of intracellular cAMP and protein kinase A in dopamine-induced inhibition of dopamine neurons and the attenuation of this inhibition by neurotensin were studied in rat midbrain slices. Spontaneous activity of dopamine cells was recorded extracellularly from both the ventral tegmental area and the substantia nigra. Perfusion of the slices with 8-bromo-cAMP and forskolin significantly attenuated dopamine-induced inhibition, but neither blocked the inhibition completely. Neither SQ22536, an inhibitor of adenylate cyclase, nor H8, an inhibitor of protein kinase A, mimicked the inhibitory effect of dopamine on dopamine neurons, although they potentiated dopamine's effect. These results indicate that dopamine-induced inhibition of dopamine neurons can be affected by intracellular cAMP levels, but is unlikely to be mediated solely by inhibition of adenylate cyclase. The similarities between the effects of neurotensin and those of 8-bromo- cAMP and forskolin suggest that intracellular cAMP may be involved in the actions of neurotensin. This suggestion is supported by our findings that isobutyl-methylxanthine (an inhibitor of phosphodiesterases) potentiated the effect of neurotensin and SQ22536 and H8 antagonized it. Phorbol-12,13-dibutyrate (an activator of protein kinase C) did not mimic the effect of neurotensin, and H7 (an inhibitor of protein kinase C) did not reduce the effect, suggesting that protein kinase C is unlikely to be involved in the modulatory effect of neurotensin.
GABA-mediated positive autofeedback loop controls horizontal cell kinetics in tiger salamander retina
Authors: Kamermans M , Werblin F
Published: March 2018

Horizontal cells (HCs) appear to release, and also to be sensitive to, GABA. The external GABA concentration is increased with depolarization of the HC membrane via an electrogenic GABA transporter. This extracellular GABA opens a GABAA-gated Cl- channel in the HC membrane. Since the equilibrium potential for Cl- (ECl) is near -20 mV, GABA released by the HC further depolarizes the HC. The GABA transporter and the GABAA receptor thus constitute a positive feedback loop in the HC membrane. This loop can slow down the kinetics of the light responses in HCs. GABA released via the GABA transporter can affect the GABAA receptor, probably because diffusion from the extracellular space is normally restricted by the intact retinal structure. We therefore used retinal slices rather than isolated HCs to maintain that structure. To measure single-cell currents in the slice, HCs were electrically uncoupled by including cAMP in the patch pipette. Under these conditions, bath application of GABA elicited two currents: (1) a picrotoxin-blocked current reversing near ECl, probably mediated by GABAA receptors, and (2) a picrotoxin-insensitive current similar to that elicited by cis-4-hydroxynipecotic acid (NIP) shown in other preparations to act at the GABA transporter. Under physiological conditions, the HC membrane potential is controlled by two major conductances, the GABAA-gated Cl- conductance described above, and the glutamate-gated conductance modulated by photoreceptor input. A bright light flash eliminates the glutamate-gated conductance, leaving only the GABA-gated Cl- conductance to control the membrane. With the Cl- conductance a significant fraction of the overall membrane conductance the GABAergic positive feedback loop can decrease the response kinetics. We increased the ambient extracellular GABA concentration by adding 50 microM GABA to the extracellular medium. This increased the ambient Cl- conductance, but the transporter still modulated Cl- conductance because responses to light stimuli were significantly slowed. The slowdown of the HC response could be reversed by interrupting the loop in two ways: (1) picrotoxin opened the loop and speeded the responses by uncoupling the GABA concentration from control of the membrane conductance, and (2) NIP opened the loop by uncoupling the extracellular GABA concentration from the Cl- conductance and therefore the membrane potential.(ABSTRACT TRUNCATED AT 400 WORDS)
Sensory tuning beyond the sensory system: an initial analysis of auditory response properties of neurons in the lateral amygdaloid nucleus and overlying areas of the striatum
Authors: Bordi F , LeDoux J
Published: March 2018

The lateral amygdaloid nucleus (AL) is anatomically connected with sensory processing structures in the thalamus and cortex and is believed to be critically involved in emotional processing by virtue of these connections. In order to understand further how auditory projections to AL contribute to emotional processing, acoustic response properties of single AL neurons were characterized in rats. Recordings were also made in the posterior striatum dorsal to AL. Many cells in AL and the striatum could be driven by broad-band auditory stimulation with white noise or clicks. Initial onset latencies were typically between 12 and 25 msec. Most cells also had later responses (60–150 msec), and a few only had late responses. In frequency receptive field tests, different classes of cells were identified. One group had relatively clear frequency preferences. Thresholds for these relatively tuned cells tended to be somewhat higher in AL than in the striatum. Frequency preferences for AL cells were always above 10 kHz. Although most striatal cells had preferences for frequencies above 10 kHz, some cells were found with frequencies below 10 kHz as well. A second group of acoustically responsive neurons, much more common in AL than in the striatum, showed no frequency specificity (untuned cells). These responded to a wide range of frequencies, even at intensities near threshold. A third group, found mainly in AL (approximately 60% of the total population of cells examined in AL), exhibited rapid habituation to auditory stimuli. These tended to have high thresholds (80–100 dB). Because these cells habituated so quickly, frequency specificity could not be determined. Responses in AL and the striatum were compared with responses in the “specific” auditory relay nucleus of the thalamus, the ventral division of the medial geniculate body, where cells had shorter onset latencies, narrower tuning functions, and lower-intensity thresholds than cells in AL and striatal areas. These findings show that cells in AL exhibit a wide range of auditory tuning properties and suggest that information processing in the amygdala might be fruitfully studied as a direct extension of processing in sensory afferent structures.