bluuebunny/crossref_metadata_2025 huggingface dataset:
Increased glutamate decarboxylase mRNA levels in the striatum and pallidum of MPTP-treated primates
Authors: Soghomonian JJ , Pedneault S , Audet G , Parent A
Published: April 2018

The mRNA levels encoding for the enzyme glutamate decarboxylase (GAD67) were measured by computerized image analysis after in situ hybridization histochemistry and radioautography in the striatum and pallidum of normal squirrel monkeys (Saimiri sciureus), or after treatment with the neurotoxin 1-methyl-4-phenyl-1,2,3,6- tetrahydropyridine (MPTP). All MPTP-injected monkeys exhibited profound motor deficits including akinesia. The dopaminergic innervation, as visualized and quantified on x-ray films after 3H-mazindol binding on tissue sections, was uniformly lost throughout the striatum of MPTP- treated monkeys. Brain sections processed with a probe synthesized from a feline or human GAD67 cDNA exhibited intense radioautographic labeling throughout the striatum. When measured on x-ray films, the intensity of GAD67 mRNA labeling was increased in the striatum of MPTP- treated versus control monkeys. Increased labeling reached statistical significance in the dorsolateral sector of the rostral putamen and throughout the putamen and the caudate at the caudal, postcommissural, level. Analysis of emulsion radioautographs demonstrated that the increase in GAD67 mRNA labeling in MPTP-treated monkeys occurred in individual neurons of the striatum. In the external and internal segments of the pallidum, numerous neurons labeled with the GAD67 cRNA probe were visualized on emulsion radioautographs. The intensity of GAD67 mRNA labeling in single neurons of both pallidal segments was increased in MPTP-treated versus control monkeys. Construction of the histograms of frequency distribution of labeling indicated that this increase occurred in a majority of labeled neurons. The present study demonstrates that GAD67 mRNA levels are significantly altered in the striatum and pallidum of parkinsonian monkeys. The preferential increase of GAD67 mRNA labeling in the dorsolateral putamen, which receives afferents from the sensorimotor cortex, provides further evidence of the involvement of GABAergic transmission in the expression of the motor deficits elicited after MPTP. In addition, increased GAD67 mRNA levels in the internal segment of the pallidum support the hypothesis of an increased activity of GABAergic neurons in the output structures of the basal ganglia in parkinsonism.
Correlations of cortical Hebbian reverberations: theory versus experiment
Authors: Amit DJ , Brunel N , Tsodyks MV
Published: April 2018

Interpreting recent single-unit recordings of delay activities in delayed match-to-sample experiments in anterior ventral temporal (AVT) cortex of monkeys in terms of reverberation dynamics, we present a model neural network of quasi-realistic elements that reproduces the empirical results in great detail. Information about the contiguity of successive stimuli in the training sequence, representing the fact that training is done on a set of uncorrelated stimuli presented in a fixed temporal sequence, is embedded in the synaptic structure. The model reproduces quite accurately the correlations between delay activity distributions corresponding to stimulation with the uncorrelated stimuli used for training. It reproduces also the activity distributions of spike rates on sample cells as a function of the stimulating pattern. It is, in our view, the first time that a computational phenomenon, represented on the neurophysiological level, is reproduced in all its quantitative aspects. The model is then used to make predictions about further features of the physiology of such experiments. Those include further properties of the correlations, features of selective cells as discriminators of stimuli provoking different delay activity distributions, and activity distributions among the neurons in a delay activity produced by a given pattern. The model has predictive implications also for the dependence of the delay activities on different training protocols. Finally, we discuss the perspectives of the interplay between such models and neurophysiology as well as its limitations and possible extensions.
TTX-sensitive dendritic sodium channels underlie oscillatory discharge in a vertebrate sensory neuron
Authors: Turner RW , Maler L , Deerinck T , Levinson SR , Ellisman MH
Published: April 2018

Immunocytochemical and electrophysiological techniques were used to localize TTX-sensitive sodium channels (NaChs) over the soma-dendritic axis of basilar and nonbasilar pyramidal cells of the electrosensory lateral line lobe (ELL) of weakly electric fish (Apteronotus leptorhynchus). Dense NaCh-like immunolabel was detected on the membranes of basilar and nonbasilar pyramidal cell somata. Punctate regions of immunolabel (approximately 15 microns) were separated by nonlabeled expanses of membrane over the entire extent of basal dendrites. Similar punctate immunolabel was observed over the apical dendrites, and frequently on membranes of afferent parallel fiber boutons in the distal apical dendritic region. Intracellular recordings from pyramidal cell somata or proximal apical dendrites (75–200 microns) were obtained using an in vitro ELL slice preparation. TTX- sensitive potentials were identified by focal pressure ejection of TTX. Somatic recordings demonstrated both TTX-sensitive fast spike discharge and a slow prepotential; similar but lower amplitude potentials were recorded in apical dendrites. Dendritic spikes were composed of at least two active components triggered by a fast prepotential (FPP) generated by the somatic spike. TTX-sensitive spikes propagated in a retrograde fashion over at least the proximal 200 microns of the apical dendrites, as determined by the conduction of an antidromic population spike and focal TTX ejections. Somatic spikes were followed by a depolarizing afterpotential (DAP) that was similar in duration and refractory period to that of proximal dendritic spikes. During repetitive spike discharge, the DAP could increase in amplitude and attain somatic spike threshold, generating a high-frequency spike doublet and a subsequent hyperpolarization that terminated spike discharge. Repetition of this process gave rise to an oscillatory burst discharge (2–6 spikes/burst) with a frequency of 40–80 Hz. Both the DAP and oscillatory discharge were selectively blocked by TTX ejections restricted to the proximal apical dendritic region. The present study demonstrates an immunolocalization of NaChs over somatic and dendritic membranes of a vertebrate sensory neuron that correlates with the distribution of TTX-sensitive potentials. The interaction of somatic and dendritic action potentials is further shown to underlie an oscillatory discharge believed to be important in electrosensory processing.
The mechanism of noradrenergic alpha 1 excitatory modulation of pontine reticular formation neurons
Authors: Stevens DR , McCarley RW , Greene RW
Published: April 2018

The alpha 1 adrenergic receptor occurs in all major divisions of the CNS and is thought to play a role in all behaviors influenced by norepinephrine (NE). In the medial pontine reticular formation (mPRF), the proposed site of adrenergic enhancement of startle responses (Davis, 1984), alpha 1 agonists excite most neurons (Gerber et al., 1990). We here report that alpha 1 excitation results from a reduction of a voltage- and calcium-dependent potassium current, not previously recognized as ligand-modulated. The calcium sensitivity is suggested by its antagonism with Mg2+, Cd2+, Ba2+, low concentrations of tetraethylammonium, and charybdotoxin. The voltage sensitivity of this conductance falls within the membrane potential range critical to action potential generation. Based on this voltage sensitivity, the change in repetitive firing characteristics may be predicted according to a mathematical model of the mPRF neuronal electrophysiology. The predicted response to a 50% decrease in the phenylephrine (PE)- sensitive conductance is similar to the observed responses, with respect to both the current response under voltage-clamp conditions and alterations of the AHP and frequency/current curve. In contrast, modeling a reduction of a voltage-insensitive leak current predicts none of these changes. Thus, the noradrenergic reduction of this current depolarizes the membrane, increases the likelihood of an initial response to depolarizing input, and increases firing rate during sustained depolarization in a manner consistent with an NE role as an excitatory neuromodulator of the mPRF.
Waiting periods versus early innervation: the development of axonal connections in the zebra finch song system
Authors: Mooney R , Rao M
Published: April 2018

This study examines the development of two neural pathways within the zebra finch forebrain that function respectively in the juvenile acquisition and the adult production of learned song. In the adult male zebra finch forebrain, the song nuclei L-MAN and HVc both innervate nucleus RA; L-MAN plays a crucial role in juvenile song acquisition but, unlike HVc and RA, is not essential for adult song production. Previous studies have shown that HVc axons arrive at the dorsal border of RA as early as posthatch day 15 (day 15), and only enter the male RA after days 25–30, but never enter the female RA. The present study examines the development of axonal projections from L-MAN to RA and finds that, in contrast to HVc axons, L-MAN terminals are present within the male and female RA by day 15, and persist there throughout adult life. Unlike RA-projecting HVc neurons, HVc neurons projecting to area X innervate this target by day 20. Like L-MAN, area X plays a transient role in song acquisition. These results suggest that in the zebra finch forebrain, neural pathways essential to juvenile song learning develop before those needed for adult song production.
Axons of early generated neurons in cingulate cortex pioneer the corpus callosum
Authors: Koester SE , O'Leary DD
Published: April 2018

The internal capsule and corpus callosum are the two major efferent axonal pathways of the mammalian neocortex. Previous studies have shown that the first cortical axons to grow through the internal capsule, the pathway from cortex to its subcortical targets, are extended by subplate neurons, which are the earliest generated neurons in the neocortex. Here, we characterize the origin of the first axons to project through the other major efferent pathway of the cortex, the midline corpus callosum, which connects the two cortical hemispheres. Using anterograde Dil tracing, we show that cortical axons first cross the midline through the nascent corpus callosum at E17. Retrograde Dil labeling from medial cortex at E18 reveals that these axons originate from a discrete group of neurons in medial (presumptive cingulate) cortex. These early callosal cells have complex morphologies with highly branched dendrites and later appear to take on a pyramidal form characteristic of callosal neurons in deep layers of cingulate cortex. 3H-thymidine birthdating demonstrates that these cells are predominantly generated on E14, making them among the earliest generated neurons in this cortical region. Injections of retrograde tracers in one cortical hemisphere at late embryonic or early postnatal ages result in substantial numbers of neurons labeled in the ipsilateral subplate, but only a few neurons labeled in the contralateral subplate. Thus, subplate neurons do not pioneer or ever project in significant numbers through the corpus callosum. We conclude that the two major efferent pathways from cortex, the corpus callosum and the internal capsule, are pioneered by developmentally and spatially distinct populations of early generated cortical neurons.
Effect of adenosine-induced changes in presynaptic release probability on long-term potentiation in the hippocampal CA1 region
Authors: Asztely F , Xiao MY , Wigstrom H , Gustafsson B
Published: April 2018

In the present study some characteristics of long-term potentiation (LTP) in the hippocampal CA1 region were examined under different conditions of transmitter release. Adenosine A1 agonist/antagonists, or in some instances changes in the extracellular calcium/magnesium ratio, were used to alter release probability. The overall LTP time course (onset latency, growth phase, and subsequent decay for both the non- NMDA and NMDA receptor-mediated EPSPs) following a brief tetanus was essentially the same over an almost 10-fold variation in release probability (measured as change in field EPSP magnitude). The major difference observed was a faster initial decay of LTP evoked at low levels of release probability, possibly related to impaired induction conditions. It was also observed that LTP induced at one level of release probability occluded that induced at a lower (or higher) level, and that changes in release probability induced by adenosine agonist/antagonists affected potentiated and “naive” EPSPs to an equal extent. Taken together, these data do not provide support for the notion of different locations for LTP expression at different conditions of release probability. The results are also more compatible with the notion of a single, rather than several, expression mechanism(s) within the first hour of LTP in the hippocampal CA1 region.
The S cell: an interneuron essential for sensitization and full dishabituation of leech shortening
Authors: Sahley CL , Modney BK , Boulis NM , Muller KJ
Published: April 2018

Sensory neurons in the leech excite the S interneuron, which in turn excites motoneurons that shorten the leech, although activity in the S cell reportedly cannot by itself shorten the animal. Experiments were performed in semi-intact leeches using established dishabituation and sensitization protocols. S-cell activity increased during reflexive shortening once the animal was sensitized or dishabituated with a strong shock. S-cell activity otherwise was not associated with shortening. To test the role of the S-cell in dishabituation and sensitization of the shortening reflex, single S cells were ablated in vivo by intracellular injections of pronase. S-cell lesions reduced but did not eliminate dishabituation; however, sensitization was completely disrupted. This was consistent with recent evidence that separate processes contribute to dishabituation and sensitization. Since the S cell in each ganglion is a link in a rapidly conducting chain along the length of the animal, it may be sufficient to break the chain at a single point to eliminate sensitization.
Activation of metabotropic glutamate receptors inhibits calcium currents and GABA-mediated synaptic potentials in striatal neurons
Authors: Stefani A , Pisani A , Mercuri NB , Bernardi G , Calabresi P
Published: April 2018

The transmitter release from GABAergic synapses is thought to be calcium (Ca2+) dependent. The pharmacological modulation of Ca2+ currents in central GABAergic neurons may strongly affect GABA release from synaptic sites. The source of striatal GABA-containing synapses is intrinsic to the striatum and mainly originates from axon collaterals of projecting medium-spiny neurons. In order to characterize the role of metabotropic glutamate receptors (mGluRs) in the modulation of central GABA release, we have combined the study of high-voltage- activated (HVA) Ca2+ currents in isolated striatal neurons with the analysis of GABA-mediated synaptic potentials evoked by local stimulation in striatal slices. The mGluR agonists t-ACPD and 1S,3R- ACPD produced a reversible and dose-dependent decrease of both HVA Ca2+ currents and GABA-mediated synaptic potentials. The mGluR-mediated inhibition of GABA-mediated synaptic potentials was not coupled with changes of the membrane responses to exogenously applied GABA, suggesting an effect on the transmitter release rather than on the GABA receptor sensitivity. The reduction of Ca2+ currents persisted in nifedipine, but not in omega-conotoxin, supporting the involvement of an N-type Ca2+ channel in this pharmacological effect. The GABA- mediated synaptic potentials were greatly reduced by omega-conotoxin. The inhibitory action of 1S,3R-ACPD on residual GABA-mediated potentials was fully occluded in the presence of omega-conotoxin. In neurons dialyzed with GTP-gamma-S, the reduction of HVA currents was irreversible, suggesting an involvement of a G-protein-mediated mechanism. Preincubation in staurosporine blocked neither the reduction of Ca2+ currents nor the inhibition of synaptic potentials induced by mGluR activation, suggesting that staurosporine-sensitive kinases are not involved in these actions. L-AP3, a noncompetitive antagonist of mGluR-mediated alteration of phosphoinositide (PI) hydrolysis, failed to block both the mGluR-mediated reduction of Ca2+ current and the inhibition of GABA-mediated synaptic potentials. We conclude that activation of mGluRs depresses intrastriatal GA-BAergic transmission and Ca2+ currents recorded from putative GABAergic striatal cells. We suggest that a reduction of Ca2+ influx in the striatal GABAergic terminal may account for the mGluR-mediated inhibition of synaptic GABA release in this structure. The modulation of GABA release by mGluRs may have a profound implication in the physiopathology of basal ganglia activity.
The glutamate uptake inhibitor L-trans-pyrrolidine-2,4-dicarboxylate depresses excitatory synaptic transmission via a presynaptic mechanism in cultured hippocampal neurons
Authors: Maki R , Robinson MB , Dichter MA
Published: April 2018

Sodium-dependent high-affinity uptake of glutamate is thought to play a major role in the maintenance of very low extracellular concentrations of excitatory amino acids (EAA), and may modulate the actions of released transmitter at G-protein-coupled receptors and extrasynaptic receptors that are activated over a longer distance and time course. We have examined the effects of the recently developed uptake inhibitor L- trans-pyrrolidine-2,4-dicarboxylate (L-trans-PDC) on monosynaptically evoked excitatory postsynaptic currents (EPSCs) in very-low-density cultures of hippocampal neurons. L-Trans-PDC produced a decreased amplitude of both the non-NMDA and NMDA receptor-mediated components of monosynaptically evoked EPSCs. Examination of miniature EPSCs (mEPSCs) indicated that changes in the sensitivity of postsynaptic non-NMDA receptors did not underline the decrease in evoked EPSC amplitudes. The metabotropic receptor agonist (1S,3R)-1-aminocyclopentane-1,3- dicarboxylic acid (1S,3R-ACPD) also depressed both components of the EPSC. The competitive metabotropic receptor antagonist (RS)-alpha- methyl-4-carboxyphenylglycine (MCPG) blocked the depression of EPSC amplitude induced by 1S,3R-ACPD and also blocked the effects of L-trans- PDC. Finally, low concentrations of L-glutamate (2 microM) mimicked the effects of L-trans-PDC on EPSC amplitude. From these results we conclude that the application of L-trans-PDC to cultured hippocampal neurons results in the activation of presynaptic metabotropic receptors, leading to a decrease in synaptic transmission. We propose that this effect is due to an increase in ambient glutamate concentrations following inhibition of glutamate uptake, resulting in presynaptic inhibition of excitatory synaptic transmission.
Cocaine inhibits GABA release in the VTA through endogenous 5-HT
Authors: Cameron DL , Williams JT
Published: April 2018

The ventral tegmental area (VTA) is thought to be involved in the addictive properties of many drugs, including cocaine. It has been hypothesized that cocaine exerts its actions in the VTA by blocking the reuptake of dopamine released from the dendrites of the A10 dopamine neurons, thus prolonging the actions of dopamine at D2 autoreceptors. However, cocaine also blocks the reuptake of the other monoamines, including serotonin (5-HT). Using intracellular recordings from midbrain dopamine neurons in a brain slice preparation, we have found that cocaine (0.1–10 microM) inhibited the GABAB IPSP in a dose- dependent manner. This effect was observed in the presence of the D2 dopamine receptor antagonists sulpiride (1 microM) and eticlopride (0.1 microM). 5-HT mimicked this effect, as did the selective 5-HT1D receptor agonist sumatriptan and the 5-HT-releasing agent fenfluramine. The actions of both 5-HT and cocaine were attenuated by the 5-HT1C/D antagonist metergoline. Pretreatment of slices with the 5-HT-depleting agent p-chloroamphetamine (pCA; 10 microM) abolished the inhibition of the GABAB IPSP by cocaine but failed to affect the actions of sumatriptan. We conclude that cocaine acts to modulate the GABA input to A10 dopamine neurons via inhibition of the 5-HT transporter, increasing the concentration of 5-HT at presynaptic 5-HT1D receptors. These actions of cocaine were apparent at lower concentrations than those required to act via inhibition of the dopamine transporter. This reduction of inhibitory synaptic input into the VTA would be expected to attenuate the GABA-mediated feedback inhibition from the nucleus accumbens, thus leading to increased activation of dopamine neurons.
Correlated quantitative studies of the neostriatum, nucleus accumbens, substantia nigra, and ventral tegmental area in normal and weaver mutant mice
Authors: Bayer SA , Triarhou LC , Thomas JD , Ghetti B
Published: April 2018

Normal mice (+/+) and homozygous weaver mutant mice (wv/wv) at 1 year of age were used for three-dimensional computer-aided reconstructions of the nucleus accumbens (NA) and neostriatum (ST) and for quantitative estimations of the total number of medium-sized neurons in the NA and ST, and for the total number of tyrosine hydroxylase (TH)-containing neurons in the ventral tegmental area (VTA) and substantia nigra (SN). The three-dimensional reconstructions showed that the weaver NA and ST are smaller than they are in +/+. Quantitative volumetric measurements of the NA and ST showed wv/wv were smaller than +/+ by nonsignificant differences of 14% and 13%, respectively. The wv/wv group showed statistically significant depletion of neurons in all four structures. On average, NA neurons are reduced by 27%, ST neurons by 22%, VTA-TH neurons by 40%, and SN-TH neurons by 79%. In wv/wv animals, there was a high positive correlation (r = 0.836) between the numbers of SN-TH neurons and ST neurons and a moderate positive correlation (r = 0.534) between the numbers of SN-VTA neurons and NA neurons. The nuclei in TH- containing neurons in wv/wv and +/+ had the same diameters, but in all animals, the SN-TH neurons contained larger nuclei than the VTA-TH neurons. Cytoarchitectonic measurements in control and weaver NA and ST were also similar. In all animals, the NA contains more densely packed neurons with smaller nuclei than those in the ST.
The oculomotor neural integrator uses a behavior-related coordinate system
Authors: Crawford JD
Published: April 2018

Coordinate systems are a central issue in computational neuroscience: are they explicitly represented at some reductive level of brain function, and if so, are they only trivial products of associated anatomic geometries? This investigation examined these questions in the neural network that holds eye position, the so-called oculomotor integrator. Since neural activity in the integrator is behaviorally constrained by Listing's law to encode horizontal and vertical eye positions within Listing's plane and zero rotation about the orthogonal torsional axis, it was hypothesized that any integrator coordinate system would be developmentally predisposed to align with Listing's plane. A test for this hypothesis was developed with the use of a kinematically correct model of the three-dimensional saccade generator. Three mathematical integrators were used to represent the neuron populations that control torsional, vertical, and horizontal eye position. Simulated failure of the torsional and vertical integrators produced eye position drift that was parallel to the horizontal plane containing the intrinsic coordinate axes for these components. Furthermore, this drift settled toward a resting range parallel to the intrinsic vertical coordinate axis (for horizontal rotation). To experimentally identify these intrinsic population coordinates, three- dimensional eye positions were measured in four Macaca fascicularis after injection of muscimol into the mesencephalic interstitial nucleus of Cajal (INC), a technique that disrupts the torsional and vertical integrators (Crawford et al., 1991). INC inactivation produced exponential, position-dependent decay in vertical and torsional eye position. There was no position-dependent horizontal drift, but in the original coordinate system (defined arbitrarily by the measurement apparatus) there was a constant-direction horizontal drift. However, this extraneous horizontal drift was eliminated when the data were transformed into a coordinate system that aligned with Listing's plane. The direction of torsional drift correlated well (r = 0.85), across all experiments, with the normal to Listing's plane. On average, these two directions were only 0.06 degrees from perfect alignment. In contrast, drift direction did not correlate with stereotaxic coordinates (r = 0.10). Furthermore, the drift settled toward a range parallel to and correlated with Listing's plane (r = 0.94), whereas this range did not correlate well with stereotaxic coordinates (r = 0.02). On average, the resting range was aligned within 0.98 degrees of Listing's plane. Finally, this resting range was near orthogonal (average 91.9 degrees across all experiments) to the direction of torsional drift. These results show that integrator cell populations use an orthogonal, craniotopic coordinate system that aligns with Listing's plane.(ABSTRACT TRUNCATED AT 250 WORDS)
An innocuous bias in whisker use in adult rats modifies receptive fields of barrel cortex neurons
Authors: Armstrong-James M , Diamond ME , Ebner FF
Published: April 2018

The effect of innocuously biasing the flow of sensory activity from the whiskers for periods of 3–30 d in awake, behaving adult rats on the receptive field organization of rat SI barrel cortex neurons was studied. One pair of adjacent whiskers, D2 and either D1 or D3, remained intact unilaterally (whisker pairing), all others being trimmed throughout the period of altered sensation. Receptive fields of single cells in the contralateral D2 barrel were analyzed under urethane anesthesia by peristimulus time histogram (PSTH) and latency histogram analysis after 3, 7–10, and 30 d of pairing and compared with controls, testing all whiskers cut to the same length. Response magnitudes to surround receptive field in-row whiskers D1 and D3 were not significantly different for control animals. The same was found for surround in-arc whiskers C2 and E2. However, after 3 d of whisker pairing a profound bias occurred in response to the paired D-row surround whisker relative to the opposite trimmed surround D-row whisker and to the C2 and E2 whiskers. This bias increased with the duration of pairing, regardless of which surround whisker (D1 or D3) was paired with D2. For all three periods of pairing the mean response to the paired surround whisker was increased relative to controls, but peaked at 7–10 d. Response to the principal center-receptive (D2) whisker was increased for the 3 and 7–10 d groups and then decreased at 30 d. Responses to trimmed arc surround whiskers (C2 and E2) were decreased in proportion to the duration of changed experience. Analysis of PSTH data showed that earliest discharges (5–10 msec poststimulus) to the D2 whisker increased progressively in magnitude with duration of pairing. For the paired surround whisker similar early discharges newly appeared after 30 d of pairing. At 3 and 7–10 d of pairing, increases in response to paired whiskers and decreases to cut surround whiskers were confined to late portions of the PSTH (10–100 msec poststimulus). Changes at 3–10 d can be attributed to alterations in intracortical synaptic relay between barrels. Longer-term changes in response to both paired whisker inputs (30 d) largely appear to reflect increases in thalamocortical synaptic efficacy. Our findings suggest that novel innocuous somatosensory experiences produce changes in the receptive field configuration of cortical cells that are consistent with Hebbian theories of experience-dependent potentiation and weakening of synaptic efficacy within SI neocortical circuitry, for correlated and uncorrelated sensory inputs, respectively.
Characterization of neurons of the supramammillary nucleus and mammillary body that discharge rhythmically with the hippocampal theta rhythm in the rat
Authors: Kocsis B , Vertes RP
Published: April 2018

We examined the activity of single cells of the supramammillary nucleus (SUM), the mammillary body (MB), and adjacent regions of the diencephalon with respect to the hippocampal electroencephalogram (EEG) in urethane-anesthetized rats. Twenty-nine of 170 cells were found to discharge synchronously with the theta rhythm of the hippocampus (theta- related neurons). All of the 29 theta-related cells were localized to the SUM or MB. A subset of theta-related cells of SUM and MB discharged in short-duration bursts comparable to the pyramidal complex spike cells of the hippocampus. In contrast to hippocampal complex spikes, however, which predominantly exhibit this mode of firing during non- theta states, the burst firing of SUM/MB cells was strongly correlated with the theta rhythm. The proportion of bursting neurons was higher in MB than in SUM. Using partial coherence analysis, we examined the relationship between SUM/MB theta-related cells and the two generators of theta of the dorsal hippocampus. The theta-related cells of MB showed a stronger correlation with “CA1” than with “dentate” theta, whereas no such asymmetry was found in the relationship between neuronal firing of SUM cells and the two generators of theta in the hippocampus. The foregoing suggests that the theta-related cells of MB are driven by descending projections from the hippocampal formation (CA1), whereas those of the SUM are not. The SUM and MB are intimately connected with the hippocampal formation--the SUM mainly via ascending projections to the dentate gyrus, and the MB via direct descending projections from the subiculum. Theta-related SUM/MB cells may be directly involved in the generation of theta and/or the transfer of theta rhythmicity to various parts of the limbic system and forebrain.
On the role of arachidonic acid in M-current modulation by muscarine in bullfrog sympathetic neurons
Authors: Villarroel A
Published: April 2018

The modulation by muscarine or LHRH of the potassium M-current (IM) in whole-cell voltage-clamped bullfrog sympathetic neurons presents an initial phase of current reduction, followed, after agonist removal, by a transient enhancement or “overrecovery.” Employing a fast solution exchange system, an inhibitory process and an enhancing process were distinguished kinetically. The extent of overrecovery increased with the extent of the preceding inhibition. The rate and degree of inhibition increased with the concentration of agonist. In contrast, the rate of recovery and the extent of overrecovery were independent. The half-lives of the inhibitory and enhancing processes were 21 and 53 sec, respectively. Several observations suggest that arachidonic acid (AA) may be involved in overrecovery: (1) AA enhanced IM in a dose- dependent and reversible manner, with an IC50 of 2.8 microM. (2) Muscarine inhibited the A-current (IA), a potassium current that is blocked by AA. (3) Phospholipase A2 inhibitors (quinacrine and bromophenacyl bromide) and a lipoxygenase inhibitor (nordihydroguaiaretic acid) prevented overrecovery, without affecting the rate or extent of IM inhibition significantly. However, kinetic analysis indicates that these drugs were preventing overrecovery by prolonging the half-life of the inhibitory process to > 80 sec (e.g., not necessarily by blocking the enhancing pathway). In addition, the extent of IA inhibition was less than expected if AA was mediating both IM enhancement and IA inhibition. The observed relation between extent and rate of overrecovery, and the action of arachidonic acid metabolism inhibitors can be accounted for by a model proposing that the agonist alters the equilibrium between three pools of M-channels.
Dual effects of angiotensin II on calcium currents in neonatal rat nodose neurons
Authors: Bacal K , Kunze DL
Published: April 2018

Angiotensin II (AII) reversibly modulates calcium current in isolated neonatal rat nodose ganglion cells by two different pathways. A maximum inhibitory effect of 43 +/- 6% (n = 25) of the peak calcium current at - 10 mV was observed at 10 nM AII. The IC50 of the inhibitory response was 100 pM. Losartan, a specific antagonist for the AT1 type of AII receptor, abolished the AII-induced inhibition, as did preincubation with pertussis toxin (PTX). When omega-conotoxin GVIA (CTX) was added to the bath solution, AII produced no inhibition of the remaining calcium current, indicating that the AII inhibition was mediated through CTX-sensitive calcium channels. Reversible facilitation of calcium current was seen more rarely. The AII-induced facilitation was unaffected by losartan and PTX, indicating that the effect is mediated by a non-AT1 receptor and does not depend upon a PTX-sensitive G- protein. The facilitation is present when the CTX-sensitive current has been blocked and involves activation of a reserve pool of dihydropyridine (DHP)-sensitive channels. In general, a particular neuron exhibited either inhibition or facilitation. However, in some neurons both inhibition and facilitation could be demonstrated in the presence of the appropriate blocking agents.
Polysynaptic regulation of glutamate receptors and mitochondrial enzyme activities in the basal ganglia of rats with unilateral dopamine depletion
Authors: Porter RH , Greene JG , Higgins DS , Greenamyre JT
Published: April 2018

After nigrostriatal dopaminergic denervation, the output nuclei of the basal ganglia, the medial globus pallidus and substantia nigra pars reticulata (Snr), become overactive, in part, because of increased activity of excitatory afferents from the subthalamic nucleus (STN). Because STN uses glutamate as a transmitter, we examined whether there are regulatory changes in glutamate receptor binding in the basal ganglia. Rats received unilateral 6-hydroxydopamine lesions of the medial forebrain bundle and substantia nigra pars compacta that were confirmed by apomorphine-induced rotation and 3H-GBR-12935 binding. As an indirect index of relative synaptic activity, succinate dehydrogenase and cytochrome oxidase activities were assayed histochemically in sections adjacent to those used for receptor binding. There were increases in enzymatic activity in entopeduncular nucleus (EP; the rodent homolog of medial globus pallidus), SNr, and globus pallidus (GP, the rodent homolog of lateral globus pallidus) in the lesioned hemisphere, suggesting increased synaptic activity, perhaps due to increased firing of the STN. Ipsilateral to the lesion, and postsynaptic to the STN, there were profound decreases in the binding of 3H-AMPA (alpha-amino-3-hydroxy-5-methylisoxazole propionic acid) in EP and SNr (45% and 30%, respectively); there were no alterations in the striatum, globus pallidus, or STN, and binding throughout the unlesioned hemisphere was equivalent to that in unlesioned control animals. In contrast, 3H-MK-801 binding to the NMDA receptor ion channel was not reduced in SNr, and was too low to be measured reliably in EP and STN. 3H-MK-801 binding was reduced by 6% in striatum and 39% in globus pallidus.(ABSTRACT TRUNCATED AT 250 WORDS)
T-cadherin expression delineates specific regions of the developing motor axon-hindlimb projection pathway
Authors: Fredette BJ , Ranscht B
Published: April 2018

T-cadherin is a unique member of the cadherin family anchored to the membrane by a glycosyl phosphatidylinositol moiety (Ranscht and Dours- Zimmermann, 1991). T-cadherin's distribution in the developing motor axon pathway was mapped by immunocytochemistry in the chick lumbosacral region as spinal neurons project to and innervate hindlimb muscle. On growing motor axons, T-cadherin was expressed biphasically. Initially, uniform T-cadherin expression occurred on motor neurons as they projected between the spinal cord and the base of the hindlimb (stage 21–24), and then decreased as the axons sorted to form dorsal, ventral and muscle nerve trunks (stage 25–27). Later, as motor axons entered and formed terminal axon arbors and synapses in muscle (stages 28–36), expression reoccurred heterogeneously among motor neuron pools. Thus, T- cadherin may guide the growth and fasciculation of all motor neurons during early axon extension, but only affect particular populations during the later expression period. In the mesenchyme of the motor axon pathway, T-cadherin was restricted to regions avoided by growing axons: the posterior-half sclerotome before and during the projection of motor axons through the T-cadherin-negative anterior half, and the extrasynaptic surfaces of developing muscle. The temporal and spatial expression patterns of T-cadherin and neurite outgrowth-promoting N- cadherin were complementary both in nerve and muscle tissues. Thus, in the posterior sclerotome and in maturing muscle, T-cadherin may act as a negative regulator that works in concert with neurite growth- promoting molecules to guide motor axons to their peripheral targets.
Inhibition of nitric oxide synthase does not prevent the induction of long-term potentiation in vivo
Authors: Bannerman DM , Chapman PF , Kelly PA , Butcher SP , Morris RG
Published: April 2018

Nitric oxide (NO), a putative intercellular messenger in the CNS, may be involved in certain forms of synaptic plasticity and learning. This article reports a series of experiments investigating whether an inhibitor of NO synthase, N omega-nitro-L-arginine methyl ester (L- NAME), affects long-term potentiation (LTP) in vivo, as the results of recent in vitro experiments would predict. L-NAME, given as an acute injection at a dose sufficient to inhibit hippocampal NO synthase (> 90%), had no effect on perforant path-dentate gyrus LTP induced by a strongly suprathreshold tetanus, but appeared to impair LTP induced by a weak near-threshold tetanus that may be more physiologically relevant. However, subsequent studies revealed that chronic L-NAME treatment (> 95% inhibition of NO synthase) had no effect upon LTP induction, and that acute (but not chronic) treatment resulted in a gradual but significant reduction in nontetanized baseline field potentials. The baseline shift appeared to be of a magnitude sufficient to account for the apparent impairment of weak tetanus-induced LTP. This possibility was further examined in a two-hemisphere experiment in which the time course of changes in the field EPSP of the nontetanized pathway served as the within-subject control for the tetanized pathway. No impairment of LTP induction was observed; indeed, if anything, there was a trend for greater potentiation with L-NAME. Because NO has also been implicated in the control of vasodilation, the effect of L-NAME on cerebrovascular function was also investigated. Peripheral blood pressure was significantly increased by L-NAME at the same dose that affected the field EPSP. Local cerebral glucose utilization was unchanged, while local cerebral blood flow decreased significantly in various brain regions, including the hippocampus, indicating an uncoupling of cerebral metabolism and blood flow. Thus, while NO synthase inhibition does not appear to limit the induction of LTP in vivo, it does reduce the size of baseline field EPSPs and affect local cerebrovascular function.
Model for the pharmacological basis of spontaneous synchronous activity in developing retinas
Authors: Burgi PY , Grzywacz NM
Published: April 2018

Spontaneous waves of bursts of action potentials propagate across the ganglion-cell surface of developing retinas. A recent biophysical model postulated that this propagation is mediated by an increase in extracellular K+, following its ejection from ganglion cells during action potentials. Moreover, the model hypothesized that bursts might terminate due to the accumulation of intracellular Ca2+ and the subsequent activation of a Ca(2+)-dependent K+ conductance in the cells' dendrites. Finally, the model proposed that an excitatory synaptic drive causes a neuromodulation of the waves' properties. To test the feasibility of the model, we performed computer simulations of the network of developing ganglion cells under control and pharmacological-manipulation conditions. In particular, we simulated the effects of neostigmine, Cs+ and TEA, low Ca2+ concentrations, and Co2+. A comparison of the simulations with electrophysiological and pharmacological experimental data recently obtained in turtles (Sernagor and Grzywacz, 1993a), and cats and ferrets (Meister et al., 1991; Wong et al., 1993), showed that the model for the most part is consistent with the behavior of developing retinas. Moreover, modifications of the model to allow for GABAergic inputs onto ganglion cells (Sernagor and Grzywacz, 1994) and poor [K+]out buffering (Connors et al., 1982) improved the model's fits. These results lent further support to important roles of extracellular K+ concentration and synaptic drive for the propagation of waves.
Modulation of the axonal microtubule cytoskeleton by myelinating Schwann cells
Authors: Kirkpatrick LL , Brady ST
Published: April 2018

The Trembler PNS myelin-deficient mutant mouse offers a unique model for the study of axon-glial interactions. Previous work in our laboratory on Trembler mouse sciatic nerve established that myelinating Schwann cells exert a profound effect on the underlying neuronal cytoskeleton. Demyelinated axon segments exhibited decreases in the rate of slow axonal transport, axonal caliber, and neurofilament phosphorylation, as well as increases in neurofilament density. The present study considers effects on the microtubule cytoskeleton. At least two aspects of the microtubule cytoskeleton in Trembler PNS axons were altered by demyelination. First, the stability of the Trembler axonal microtubule cytoskeleton is decreased, as measured by decreased levels of insoluble tubulin (Sahenk and Brady, 1987). Second, the composition and phosphorylation of axonal microtubule-associated proteins, including tau, MAP 1A, and MAP 1B, are changed in Trembler demyelinated nerves. Further, the fraction of axonal tubulin moving at slow component b rates was increased (de Waegh and Brady 1990, 1991). These results provide further evidence that cell-cell interactions between myelinating glia and their underlying axons extend beyond a structural role, actively influencing biochemical and physiological properties of the axon.
Age-related decrease of GABAA receptor subunits and glutamic acid decarboxylase in the rat inferior colliculus
Authors: Gutierrez A , Khan ZU , Morris SJ , De Blas AL
Published: April 2018

A selective age-related decrease in both the protein and mRNA levels of the most abundant GABAA receptor subunits has been revealed in the rat inferior colliculus. The number (not affinity) of the native and fully assembled GABAA receptors assayed by 3H-muscimol binding was also decreased (35–49%). The decrease in GABA receptors was accompanied by a decrease in the protein and mRNA of the GABA-synthesizing enzyme glutamic acid decarboxylase. No other region of the rat brain showed such large age-related changes in these GABAergic synaptic molecules. Specific antibodies and riboprobes in conjunction with a computerized image analysis system were used to quantify immunocytochemistry and in situ hybridization. In old Sprague-Dawley rats, the combination of beta 2 and beta 3 peptide subunits was reduced 55%, while the beta 2 and beta 3 mRNAs were decreased 31% and 22%, respectively. The gamma 2S and gamma 2L subunit proteins decreased 43% and 21%, respectively, while the gamma 2 mRNA, including both short and long forms, was reduced 61%. The alpha 1 subunit protein was decreased 28%, whereas the alpha 1 mRNA decreased 40%. The glutamic acid decarboxylase protein was reduced 62% while GAD65 mRNA decreased 42%. Similar age-related changes were also observed in the inferior colliculus of Fischer-344 rats. In contrast, no changes were observed in the level of expression of some glial and/or neuronal proteins such as S-100, glial fibrillary acidic protein, and 160 KDa neurofilament protein in the inferior colliculus.(ABSTRACT TRUNCATED AT 250 WORDS)
Postnatal development of the tyrosine hydroxylase-containing cell population within the rat locus coeruleus: topological organization andphenotypic plasticity
Authors: Bezin L , Marcel D , Debure LI , Ginovart N , Rousset C , Pujol JF , Weissmann D
Published: April 2018

The cellular phenotypic characteristics of tyrosine hydroxylase (TH) expression have been studied within the rat locus coeruleus (LC) during postnatal development at six different stages: postnatal day 4 (PND4), PND10, PND14, PND21, PND30, and PND42. Coronal brain sections were selected at intervals of 80 microns along the caudorostral extent of the LC and processed for TH immunohistochemistry. At each anatomical level we (1) reconstructed the mean space of the LC delineated by the TH positive cell bodies, (2) enumerated the mean number of these cell bodies, and (3) determined the mean volume circumscribed by these cell bodies and their density. The topological study revealed a steady remodeling of the structure until the third week, with a progressive reducing of a ventral cellular group in the anterior LC, which was no longer observable at PND21, concomitant to the stretch of the structure toward its caudal limit. We have noted invariant and variant cellular phenotypic characteristics of TH expression. At any stage, the LC could be separated into a posterior and an anterior subregion and its total volume remained quite stable during the studied period. At PND14 and PND21, we observed a transient 33% increase in the total number of TH positive perikarya as compared to PND42. Conjoint analysis of the topological reconstruction and the density of TH positive cells suggested there were three distinct and precisely localized subsets of “quiescent” neurons. TH gene expression in these cells would have lowered between PND14 and PND21 inside two subsets and between PND21 and PND30 inside the last one. So topologically defined populations of cells could be involved in specific functions. If they have not definitively lost their TH expression capacity, they could contribute to increasing TH levels in LC occurring in response to physiological perturbations or pharmacological treatments.