bluuebunny/crossref_metadata_2025 huggingface dataset:
Dorsal Column Nuclei Neurons Recorded in a Brain Stem–Spinal Cord Preparation: Characteristics and Their Responses to Dorsal Root Stimulation
Authors: Deuchars Susan A. , Trippenbach T. , Spyer K. Michael
Published: December 2017

Recordings were obtained from dorsal column nucleus (DCN) neurons in a neonatal rat brain stem—spinal cord preparation to study their basic electrophysiological properties and responses to stimulation of a dorsal root. Whole-cell patch-clamp recordings were made from 21 neurons that responded to dorsal root stimulation with a fast excitatory postsynaptic potential (EPSP). These neurons were located lateral to, but at the level of, the area postrema at depths of 100–268 μm below the dorsal surface of the brain. The neurons could be divided into groups according to the shape of their action potentials or voltage responses to hyperpolarizing current steps; however, the response profiles of the groups of neurons to dorsal root stimulation were not significantly different and all neurons were considered together. Dorsal root stimulation elicited excitatory postsynaptic potentials (EPSPs) in all neurons with a very low variability in onset latency and an ability to follow 100-Hz stimulation, indicating that they were mediated by activation of a monosynaptic pathway. The peak amplitude of the EPSP increased with membrane hyperpolarization, and applications of the non-NMDA receptor antagonists 6-nitro-7-sulfamoylbenzo[f]quinoxaline-2,3-dione (NBQX) and 6,7-dinitroquinoxaline-2,3-dione (DNQX) decreased the amplitude of the EPSP to 14.2% of the control response ( n = 6). The descending phase of the EPSP decreased with membrane hyperpolarization and was reduced by the N-methyl-d-aspartate (NMDA) receptor antagonist AP-5 ( n = 2). The EPSPs were also reduced in amplitude by applications of the γ-aminobutyric acid-B (GABAB) receptor agonist baclofen, which had no effect on membrane potential or input resistance. These results show that fast EPSPs in DCN neurons elicited by dorsal root stimulation are mediated by an excitatory amino acid acting at both non-NMDA and, to a lesser extent, NMDA receptors. In addition, GABA acting at presynaptic GABAB receptors can inhibit these responses.
Persistent Activation of GABAAReceptor/Cl− Channels by Astrocyte-Derived GABA in Cultured Embryonic Rat Hippocampal Neurons
Authors: Liu Qi-Ying , Schaffner Anne E. , Chang Yoong H. , Maric Dragan , Barker Jeffery L.
Published: December 2017

Whole cell patch-clamp recordings using Cl−-filled pipettes revealed more negative levels of baseline current and associated current variance in embryonic rat hippocampal neurons co-cultured on a monolayer of astrocytes than those cultured on poly-d-lysine. These effects were mimicked by culturing neurons on poly-d-lysine in astrocyte-conditioned medium (ACM). The baseline current and variance decreased immediately in all cells after either local perfusion with saline or exposure to bicuculline, an antagonist of GABA at GABAAreceptor/Cl− channels. Baseline current and variance in all cells reached a nadir at ∼0 mV, the calculated equilibrium potential for Cl−. Perfusion of ACM rapidly induced a sustained current in neurons, which also reversed polarity at ∼0 mV. Bicuculline attenuated or eliminated the ACM-induced current at a concentration that completely blocked micromolar GABA-induced current. Quantitative analyses of spontaneously occurring fluctuations superimposed on the ACM-induced current revealed estimated unitary properties of the underlying channel activity similar to those calculated for GABA's activation of GABAA receptor/Cl−channels. Bicuculline-sensitive synaptic-like transients, which reversed at ∼0 mV, were also detected in neurons cultured in ACM, and these were immediately eliminated along with the negative baseline current and superimposed current fluctuations by perfusion. Furthermore bicuculline-sensitive synaptic-like transients were rapidly and reversibly triggered when ACM was acutely applied. ACM induced an increase in cytoplasmic Ca2+ in cultured embryonic hippocampal neurons that was completely blocked by bicuculline and strychnine. We conclude that astrocytes release diffusible substances, most likely GABA, that persistently activate GABAA receptor/Cl−channels in co-cultured neurons.
Fingertip Contact Suppresses the Destabilizing Influence of Leg Muscle Vibration
Authors: Lackner James R. , Rabin Ely , DiZio Paul
Published: December 2017

Touch of the hand with a stationary surface at nonmechanically supportive force levels (<1 N) greatly attenuates postural sway during quiet stance. We predicted such haptic contact would also suppress the postural destabilization caused by vibrating the right peroneus brevis and longus muscles of subjects standing heel-to-toe with eyes closed. In experiment 1, ten subjects were tested under four conditions: no-vibration, no-touch; no-vibration, touch; vibration, no-touch; and vibration, touch. A hand-held physiotherapy vibrator (120 Hz) was applied ∼5 cm above the malleolous to stimulate the peroneus longus and brevis tendons. Touch conditions involved contact of the right index finger with a laterally positioned surface (<1 N of force) at waist height. Vibration in the absence of finger contact greatly increased the mean sway amplitude of the center of pressure and of the head relative to the no-vibration, no-touch control condition ( P < 0.001). The touch, no-vibration and touch-vibration conditions were not significantly different ( P > 0.05) from each other and both had significantly less mean sway amplitude of head and of center of pressure than the other conditions ( P < 0.01). In experiment 2, eight subjects stood heel-to-toe under touch and no-touch conditions involving 40-s duration trials of peroneus tendon vibration at different duty cycles: 1-, 2-, 3-, and 4-son and off periods. The vibrator was attached to the subject's leg and remotely activated. In the no-touch conditions, subjects showed periodic postural disruptions contingent on the duty cycle and mirror image rebounds with the offset of vibration. In the touch conditions, subjects were much less disrupted and showed compensations occurring within 500 ms of vibration onset and mirror image rebounds with vibration offset. Subjects were able to suppress almost completely the destabilizing influence of the vibration in the 3- and 4-s duty cycle trials. These experiments show that haptic contact of the hand with a stable surface can suppress abnormal proprioceptive and motor signals in leg muscles.
Effects of Nucleus Prepositus Hypoglossi Lesions on Visual Climbing Fiber Activity in the Rabbit Flocculus
Authors: Arts M. P. , De Zeeuw C. I. , Lips J. , Rosbak E. , Simpson J. I.
Published: December 2017

The caudal dorsal cap (dc) of the inferior olive is involved in the control of horizontal compensatory eye movements. It provides those climbing fibers to the vestibulocerebellum that modulate optimally to optokinetic stimulation about the vertical axis. This modulation is mediated at least in part via an excitatory input to the caudal dc from the pretectal nucleus of the optic tract and the dorsal terminal nucleus of the accessory optic system. In addition, the caudal dc receives a substantial GABAergic input from the nucleus prepositus hypoglossi (NPH). To investigate the possible contribution of this bilateral inhibitory projection to the visual responsiveness of caudal dc neurons, we recorded the climbing fiber activity (i.e., complex spikes) of vertical axis Purkinje cells in the flocculus of anesthetized rabbits before and after ablative lesions of the NPH. When the NPH ipsilateral to the recorded flocculus was lesioned, the spontaneous complex spike firing frequency did not change significantly; but when both NPHs were lesioned, the spontaneous complex spike firing frequency increased significantly. When only the contralateral NPH was lesioned, the spontaneous complex spike firing frequency decreased significantly. Neither unilateral nor bilateral lesions had a significant influence on the depth of complex spike modulation during constant velocity optokinetic stimulation or on the transient continuation of complex spike modulation that occurred when the constant velocity optokinetic stimulation stopped. The effects of the lesions on the spontaneous complex spike firing frequency could not be explained when only the projections from the NPH to the inferior olive were considered. Therefore we investigated at the electron microscopic level the nature of the commissural connection between the two NPHs. The terminals of this projection were found to be predominantly GABAergic and to terminate in part on GABAergic neurons. When this inhibitory commissural connection is taken into consideration, then the effects of NPH lesions on the spontaneous firing frequency of floccular complex spikes are qualitatively explicable in terms of relative weighting of the commissural and caudal dc projections of the NPH. In summary, we conclude that in the anesthetized rabbit the inhibitory projection of the NPH to the caudal dc influences the spontaneous firing frequency of floccular complex spikes but not their modulation by optokinetic stimulation.
Functional Expression of L-, N-, P/Q-, and R-Type Calcium Channels in the Human NT2-N Cell Line
Authors: Neelands Torben R. , King Anthony P. J. , Macdonald Robert L.
Published: December 2017

The biophysical and pharmacological properties of voltage-gated calcium channel currents in the human teratocarcinoma cell line NT2-N were studied using the whole cell patch-clamp technique. When held at −80 mV, barium currents ( IBas) were evoked by voltage commands to above −35 mV that peaked at +5 mV. When holding potentials were reduced to −20 mV or 5 mM barium was substituted for 5 mM calcium, there was a reduction in peak currents and a right shift in the current-voltage curve. A steady-state inactivation curve for IBawas fit with a Boltzmann curve ( V1/2= −43.3 mV; slope = −17.7 mV). Maximal current amplitude increased from 1-wk (232 pA) to 9-wk (1025 pA) postdifferentiation. Whole cell IBas were partially blocked by specific channel blockers to a similar extent in 1- to 3-wk and 7- to 9-wk postdifferentiation NT2-N cells: 10 μM nifedipine (19 vs. 25%), 10 μM conotoxin GVIA (27 vs. 25%), 10 μM conotoxin MVIIC (15 vs. 16%), and 1.75 μM SNX-482 (31 vs. 33%). Currents were completely blocked by 300 μM cadmium. In the presence of nifedipine, GVIA, and MVIIC, ∼35% of current remained, which was reduced further by SNX-482 (7–14% of current remained), consistent with functional expression of L-, N-, and P/Q-calcium channel types and one or more R-type channel. The presence of multiple calcium currents in this human neuronal-type cell line provides a potentially useful model for study of the regulation, expression and cellular function of human derived calcium channel currents; in particular the R-type current(s).
Slow Dorsal-Ventral Rhythm Generator in the Lamprey Spinal Cord
Authors: Aoki Fumi , Wannier Thierry , Grillner Sten
Published: December 2017

In the isolated lamprey spinal cord, a very slow rhythm (0.03–0.11 Hz), superimposed on fast N-methyl-d-aspartate (NMDA)-induced locomotor activity (0.26–2.98 Hz), could be induced by a blockade of GABAAor glycine receptors or by administration of (1 s, 3 s)-l-aminocyclopentane-1,3-dicarboxylic acid a metabotropic glutamate receptor agonist. Ventral root branches supplying dorsal and ventral myotomes were exposed bilaterally to study the motor pattern in detail. The slow rhythm was expressed in two main forms: 1) a dorsal-ventral reciprocal pattern was the most common (18 of 24 preparations), in which bilateral dorsal branches were synchronous and alternated with the ventral branches, in two additional cases a diagonal dorsal-ventral reciprocal pattern with alternation between the left (or right) dorsal and the right (or left) ventral branches was observed; 2) synchronous bursting in all branches was encountered in four cases. In contrast, the fast locomotor rhythm occurred always in a left-right reciprocal pattern. Thus when the slow rhythm appeared in a dorsal-ventral reciprocal pattern, fast rhythms would simultaneously display left-right alternation. A longitudinal midline section of the spinal cord during ongoing slow bursting abolished the reciprocal pattern between ipsilateral dorsal and ventral branches but a synchronous burst activity could still remain. The fast swimming rhythm did not recover after the midline section. These results suggest that in addition to the network generating the swimming rhythm in the lamprey spinal cord, there is also a network providing slow reciprocal alternation between dorsal and ventral parts of the myotome. During steering, a selective activation of dorsal and ventral myotomes is required and the neural network generating the slow rhythm may represent activity in the spinal machinery used for steering.
Mechanisms Underlying Stabilization of Temporally Summated Muscle Contractions in the Lobster (Panulirus) Pyloric System
Authors: Morris Lee G. , Hooper Scott L.
Published: December 2017

Muscles are the final effectors of behavior. The neural basis of behavior therefore cannot be completely understood without a description of the transfer function between neural output and muscle contraction. To this end, we have been studying muscle contraction in the well-investigated lobster pyloric system. We report here the mechanisms underlying stabilization of temporally summating contractions of the very slow dorsal dilator muscle in response to motor nerve stimulation with trains of rhythmic shock bursts at a physiological intraburst spike frequency (60 Hz), physiological cycle periods (0.5–2 s), and duty cycles from 0.1 to 0.8. For temporal summation to stabilize, the rise and relaxation amplitudes of the phasic contractions each burst induces must equalize as the rhythmic train continues. Stabilization could occur by changes in rise duration, rise slope, plateau duration, and/or relaxation slope. We demonstrate a generally applicable method for quantifying the relative contribution changes in these characteristics make to contraction stabilization. Our data show that all characteristics change as contractions stabilize, but their relative contribution differs depending on stimulation cycle period and duty cycle. The contribution of changes in rise duration did not depend on period or duty cycle for the 1-, 1.5-, and 2-s period regimes, contributing ∼30% in all cases; but for the 0.5-s period regime, changes in rise duration increased from contributing 25% to contributing 50% as duty cycle increased from 0.1 to 0.8. At all cycle periods decreases in rise slope contributed little to stabilization at small duty cycles but increased to contributing ∼80% at high duty cycles. The contribution of changes in plateau duration decreased in all cases as duty cycle increased; but this decrease was greater in long cycle period regimes. The contribution of changes in relaxation slope also decreased in all cases as duty cycle increased; but for this characteristic, the decrease was greatest in fast cycle period regimes, and in these regimes at high duty cycles these changes opposed contraction stabilization. Exponential fits to contraction relaxations showed that relaxation time constant increased with total contraction amplitude; this increase presumably underlies the decreased relaxation slope magnitude seen in high duty cycle, fast cycle period regimes. These data show that changes in no single contraction characteristic can account for contraction stabilization in this muscle and suggest that predicting muscle response in other systems in which slow muscles are driven by rapidly varying neuronal inputs may be similarly complex.
Modulation of Ca2+ Signaling by K+Channels in a Hypothalamic Neuronal Cell Line (GT1–1)
Authors: Costantin James L. , Charles Andrew C.
Published: December 2017

The pulsatile release of gonadotropin releasing hormone (GnRH) is driven by the intrinsic activity of GnRH neurons, which is characterized by bursts of action potentials correlated with oscillatory increases in intracellular Ca2+. The role of K+ channels in this spontaneous activity was studied by examining the effects of commonly used K+ channel blockers on K+currents, spontaneous action currents, and spontaneous Ca2+signaling. Whole-cell recordings of voltage-gated outward K+ currents in GT1–1 neurons revealed at least two different components of the current. These included a rapidly activating transient component and a more slowly activating, sustained component. The transient component could be eliminated by a depolarizing prepulse or by bath application of 1.5 mM 4-aminopyridine (4-AP). The sustained component was partially blocked by 2 mM tetraethylammonium (TEA). GT1–1 cells also express inwardly rectifying K+ currents ( I K(IR)) that were activated by hyperpolarization in the presence of elevated extracellular K+. These currents were blocked by 100 μM Ba2+ and unaffected by 2 mM TEA or 1.5 mM 4-AP. TEA and Ba2+ had distinct effects on the pattern of action current bursts and the resulting Ca2+ oscillations. TEA increased action current burst duration and increased the amplitude of Ca2+ oscillations. Ba2+ caused an increase in the frequency of action current bursts and Ca2+oscillations. These results indicate that specific subtypes of K+ channels in GT1–1 cells can have distinct roles in the amplitude modulation or frequency modulation of Ca2+signaling. K+ current modulation of electrical activity and Ca2+ signaling may be important in the generation of the patterns of cellular activity responsible for the pulsatile release of GnRH.
Imaging Anoxic Depolarization During Ischemia-Like Conditions in the Mouse Hemi-Brain Slice
Authors: Joshi I. , Andrew R. D.
Published: December 2017

Focal ischemia evokes a sudden loss of membrane potential in neurons and glia of the ischemic core termed the anoxic depolarization (AD). In metabolically compromised regions with partial blood flow, peri-infarct depolarizations (PIDs) further drain energy reserves, promoting acute and delayed neuronal damage. Visualizing and quantifying the AD and PIDs and their acute deleterious effects are difficult in the intact animal. In the present study, we imaged intrinsic optical signals to measure changes in light transmittance in the mouse coronal hemi-brain slice during AD generation. The AD was induced by oxygen/glucose deprivation (OGD) or by ouabain exposure. Potential neuroprotective strategies using glutamate receptor antagonists or reduced temperature were tested. Eight minutes of OGD ( n = 18 slices) or 4 min of 100 μM ouabain ( n = 14) induced a focal increase of increased light transmittance (LT) in neocortical layers II/III that expanded concentrically to form a wave front coursing through neocortex and independently through striatum. The front was coincident with a negative voltage shift in extracellular potential. Wherever the LT front (denoting cell swelling) propagated, a decrease in LT (denoting dendritic beading) followed in its wake. In addition the evoked field potential was permanently lost, indicating neuronal damage. Glutamate receptor antagonists did not block the onset and propagation of AD or the extent of irreversible damage post-AD. Lowering temperature to 25–30°C protected the tissue from OGD damage by inhibiting AD onset. This study shows that anoxic depolarization evoked by global ischemia-like conditions is a spreading process that is focally initiated at multiple sites in cortical and subcortical gray. The combined energy demands of O2/glucose deprivation and the AD greatly exacerbate neuronal damage. Glutamate receptor antagonists neither block the AD in the ischemic core nor, we propose, block recurrent PID arising close to the core.
Amplification and Linear Summation of Synaptic Effects on Motoneuron Firing Rate
Authors: Prather Jonathan F. , Powers Randall K. , Cope Timothy C.
Published: December 2017

The aim of this study was to measure the effects of synaptic input on motoneuron firing rate in an unanesthetized cat preparation, where activation of voltage-sensitive dendritic conductances may influence synaptic integration and repetitive firing. In anesthetized cats, the change in firing rate produced by a steady synaptic input is approximately equal to the product of the effective synaptic current measured at the resting potential ( IN) and the slope of the linear relation between somatically injected current and motoneuron discharge rate ( f-I slope). However, previous studies in the unanesthetized decerebrate cat indicate that firing rate modulation may be strongly influenced by voltage-dependent dendritic conductances. To quantify the effects of these conductances on motoneuron firing behavior, we injected suprathreshold current steps into medial gastrocnemius motoneurons of decerebrate cats and measured the changes in firing rate produced by superimposed excitatory synaptic input. In the same cells, we measured INand the f-I slope to determine the predicted change in firing rate (Δ F = IN* f-I slope). In contrast to previous results in anesthetized cats, synaptically induced changes in motoneuron firing rate were greater-than-predicted. This enhanced effect indicates that additional inward current was present during repetitive firing. This additional inward current amplified the effective synaptic currents produced by two different excitatory sources, group Ia muscle spindle afferents and caudal cutaneous sural nerve afferents. There was a trend toward more prevalent amplification of the Ia input (14/16 cells) than the sural input (11/16 cells). However, in those cells where both inputs were amplified (10/16 cells), amplification was similar in magnitude for each source. When these two synaptic inputs were simultaneously activated, their combined effect was generally very close to the linear sum of their amplified individual effects. Linear summation is also observed in medial gastrocnemius motoneurons of anesthetized cats, where amplification is not present. This similarity suggests that amplification does not disturb the processes of synaptic integration. Linear summation of amplified input was evident for the two segmental inputs studied here. If these phenomena also hold for other synaptic sources, then the presence of active dendritic conductances underlying amplification might enable motoneurons to integrate multiple synaptic inputs and drive motoneuron firing rates throughout the entire physiological range in a relatively simple fashion.
Direct Actions of Cannabinoids on Synaptic Transmission in the Nucleus Accumbens: A Comparison With Opioids
Authors: Hoffman Alexander F. , Lupica Carl R.
Published: December 2017

The nucleus accumbens (NAc) represents a critical site for the rewarding and addictive properties of several classes of abused drugs. The medium spiny GABAergic projection neurons (MSNs) in the NAc receive innervation from intrinsic GABAergic interneurons and glutamatergic innervation from extrinsic sources. Both GABA and glutamate release onto MSNs are inhibited by drugs of abuse, suggesting that this action may contribute to their rewarding properties. To investigate the actions of cannabinoids in the NAc, we performed whole cell recordings from MSNs located in the shell region in rat brain slices. The cannabinoid agonist WIN 55,212-2 (1 μM) had no effect on the resting membrane potential, input resistance, or whole cell conductance, suggesting no direct postsynaptic effects. Evoked glutamatergic excitatory postsynaptic currents (EPSCs) were inhibited to a much greater extent by [Tyr-d-Ala2, N-CH3-Phe4, Gly-ol-enkephalin] (DAMGO, ∼35%) than by WIN 55,212-2 (<20%), and an analysis of miniature EPSCs suggested that the effects of DAMGO were presynaptic, whereas those of WIN 55,212-2 were postsynaptic. However, electrically evoked GABAergic inhibitory postsynaptic currents (evIPSCs), were reduced by WIN 55,212-2 in every neuron tested (EC50 = 123 nM; 60% maximal inhibition), and the inhibition of IPSCs by WIN 55,212-2 was completely antagonized by the CB1 receptor antagonist SR141716A (1 μM). In contrast evIPSCs were inhibited in ∼50% of MSNs by the μ/δ opioid agonistd-Ala2-methionine2-enkephalinamide and were completely unaffected by a selective μ-opioid receptor agonist (DAMGO). WIN 55,212-2 also increased paired-pulse facilitation of the evIPSCs and did not alter the amplitudes of tetrodotoxin-resistant miniature IPSCs, suggesting a presynaptic action. Taken together, these data suggest that cannabinoids and opioids differentially modulate inhibitory and excitatory synaptic transmission in the NAc and that the abuse liability of marijuana may be related to the direct actions of cannabinoids in this structure.
Multisensory Cortical Signal Increases and Decreases During Vestibular Galvanic Stimulation (fMRI)
Authors: Bense Sandra , Stephan Thomas , Yousry Tarek A. , Brandt Thomas , Dieterich Marianne
Published: December 2017

Functional magnetic resonance imaging blood-oxygenation-level-dependent (BOLD) signal increases (activations) and BOLD signal decreases (“deactivations”) were compared in six healthy volunteers during galvanic vestibular (mastoid) and galvanic cutaneous (neck) stimulation in order to differentiate vestibular from ocular motor and nociceptive functions. By calculating the contrast for vestibular activation minus cutaneous activation for the group, we found activations in the anterior parts of the insula, the paramedian and dorsolateral thalamus, the putamen, the inferior parietal lobule [Brodmann area (BA) 40], the precentral gyrus (frontal eye field, BA 6), the middle frontal gyrus (prefrontal cortex, BA 46/9), the middle temporal gyrus (BA 37), the superior temporal gyrus (BA 22), and the anterior cingulate gyrus (BA 32) as well as in both cerebellar hemispheres. These activations can be attributed to multisensory vestibular and ocular motor functions. Single-subject analysis in addition showed distinctly nonoverlapping activations in the posterior insula, which corresponds to the parieto-insular vestibular cortex in the monkey. During vestibular stimulation, there was also a significant signal decrease in the visual cortex (BA 18, 19), which spared BA 17. A different “deactivation” was found during cutaneous stimulation; it included upper parieto-occipital areas in the middle temporal and occipital gyri (BA 19/39/18). Under both stimulation conditions, there were signal decreases in the somatosensory cortex (BA 2/3/4). Stimulus-dependent, inhibitory vestibular-visual, and nociceptive-somatosensory interactions may be functionally significant for processing perception and sensorimotor control.
Axonal L-Type Ca2+ Channels and Anoxic Injury in Rat CNS White Matter
Authors: Brown Angus M. , Westenbroek Ruth E. , Catterall William A. , Ransom Bruce R.
Published: December 2017

We studied the magnitude and route(s) of Ca2+ flux from extra- to intracellular compartments during anoxia in adult rat optic nerve (RON), a central white matter tract, using Ca2+-sensitive microelectrodes to monitor extracellular [Ca2+] ([Ca2+]o). One hour of anoxia caused a rapid loss of the stimulus-evoked compound action potential (CAP), which partially recovered following re-oxygenation, indicating that irreversible injury had occurred. After an initial increase caused by extracellular space shrinkage, anoxia produced a sustained decrease of 0.42 mM (29%) in [Ca2+]o. We quantified the [Ca2+]o decrease as the area below baseline [Ca2+]o during anoxia and used this as a qualitative index of suspected Ca2+ influx. The degree of RON injury was predicted by the amount of Ca2+ leaving the extracellular space. Bepridil, 0 Na+ artificial cerebrospinal fluid or tetrodotoxin reduced suspected Ca2+ influx during anoxia implicating reversal of the Na+-Ca2+ exchanger as a route of Ca2+ influx. Diltiazem reduced suspected Ca2+ influx during anoxia, suggesting that Ca2+ influx via L-type Ca2+channels is a route of toxic Ca2+ influx into axons during anoxia. Immunocytochemical staining was used to demonstrate and localize high-threshold Ca2+channels. Only α1C and α1D subunits were detected, indicating that only L-type Ca2+ channels were present. Double labeling with anti-neurofilament antibodies or anti-glial fibrillary acidic protein antibodies, localized L-type Ca2+channels to axons and astrocytes.
Kappa Opioid Receptor Inhibition of Glutamatergic Transmission in the Nucleus Accumbens Shell
Authors: Hjelmstad Gregory O. , Fields Howard L.
Published: December 2017

Microinjection of κ-opioid receptor agonists into the nucleus accumbens produces conditioned place aversion. While attention has focused primarily on the inhibition of dopamine release by κ-receptor agonists as the synaptic mechanism underlying this effect, recent anatomical studies have raised the possibility that regulation of noncatecholaminergic transmission also contribute. We have investigated the effects of κ-receptor activation on fast excitatory synaptic transmission in an in vitro slice preparation using whole cell voltage-clamp or extracellular field recordings in the shell region of the nucleus accumbens. The κ-receptor agonist U69593 produces a pronounced, dose-dependent inhibition of glutamatergic excitatory postsynaptic currents (EPSCs) that can be reversed by 100 nM nor-BNI. Furthermore, U69593 causes an increase in the paired-pulse ratio as well as a decrease in the frequency of spontaneous miniature events, suggesting a presynaptic site of action. Despite anatomical evidence for κ-receptor localization on dendritic spines of nucleus accumbens neurons, no electrophysiological evidence of a postsynaptic effect was found. This presynaptic inhibition of excitatory synaptic transmission in the nucleus accumbens shell provides a novel mechanism that may contribute to the κ-receptor–mediated aversion observed in intact animals.
Cellular Mechanisms of Thalamically Evoked Gamma Oscillations in Auditory Cortex
Authors: Sukov William , Barth Daniel S.
Published: December 2017

The purpose of this study was to clarify the neurogenesis of thalamically evoked gamma frequency (∼40 Hz) oscillations in auditory cortex by comparing simultaneously recorded extracellular and intracellular responses elicited with electrical stimulation of the posterior intralaminar nucleus of the thalamus (PIL). The focus of evoked gamma activity was located between primary and secondary auditory cortex using a 64-channel epipial electrode array, and all subsequent intracellular recordings and single-electrode field potential recordings were made at this location. These data indicate that PIL stimulation evokes gamma oscillations in auditory cortex by tonically depolarizing pyramidal cells in the supra- and infragranular layers. No cells revealed endogenous membrane properties capable of producing activity in the gamma frequency band when depolarized individually with injected current, but all displayed both sub- and supra-threshold responses time-locked to extracellular fast oscillations when the population was depolarized by PIL stimulation. We propose that cortical gamma oscillations may be produced and propagated intracortically by network interactions among large groups of neurons when mutually excited by modulatory input from the intralaminar thalamus and that these oscillations do not require specialized pacemaker cells for their neurogenesis.
Bilateral Interactions During Contractions of Intrinsic Hand Muscles
Authors: Zijdewind Inge , Kernell Daniel
Published: December 2017

During demanding voluntary contractions (e.g., high force or fatigue), activation is not restricted to the target muscle but extends to other ipsilateral muscles; even contralateral muscles become activated. The contralateral “irradiation” of activity was measured in five subjects during submaximal and maximal voluntary contractions (MVCs) of the first dorsal interosseous (FDI) (index finger abduction) and during unfatigued and fatigued conditions. All subjects were tested five times with at least one week between tests. Unilateral MVCs were associated with a substantial amount of contralateral FDI activation [mean = 7.9 ± 6.7% (SD) MVC prior to fatigue]. The amount of such contralateral irradiation was significantly different between different individuals and was positively correlated between dominant and nondominant hands. During fatigue tests, the contractile activity of the contralateral “nontarget” index finger showed progressive increase (force, electromyogram) as was measured during both the submaximal task and interspersed MVCs of the target finger. In addition, a superimposed saw-tooth pattern of intermittently waxing and waning contractions commonly appeared contralaterally. The expression of contralateral irradiation force was itself fatigue-sensitive: less irradiation was seen in a recently fatigued muscle than was seen before the fatigue test. These fatigue effects could not be explained as having been caused by changes in muscle properties. Possible anatomical sites of contralateral irradiation are briefly discussed.
A Possible Explanation for a Neurotoxic Effect of the Anticancer Agent Oxaliplatin on Neuronal Voltage-Gated Sodium Channels
Authors: Grolleau Françoise , Gamelin Laurence , Boisdron-Celle Michèle , Lapied Bruno , Pelhate Marcel , Gamelin Erick
Published: December 2017

Oxaliplatin, a new widely used anticancer drug, displays frequent, sometimes severe, acute sensory neurotoxicity accompanied by neuromuscular signs that look like the symptoms observed in tetany and myotonia. The whole cell patch-clamp technique was employed to investigate the oxaliplatin effects on the electrophysiological properties of short-term cultured dorsal unpaired median (DUM) neurons isolated from the CNS of the cockroach Periplaneta americana. Within the clinical concentration range, oxaliplatin (40–500 μM), applied intracellularly, decreased the amplitude of the voltage-gated sodium current resulting in a reduction of half the amplitude of the action potential. For comparison, two other platinum derivatives, cisplatin and carboplatin, were found to be ineffective at reducing the sodium current amplitude. In addition, we compared the oxaliplatin action to those of its metabolites dichloro-diaminocyclohexane platinum (dach-Cl2-platin) and oxalate. Oxalate (500 μM) was found to be effective, like oxaliplatin, at reducing the inward sodium current amplitude, whereas dach-Cl2-platin (500 μM) failed to change the current amplitude. Interestingly, the effect of oxalate or oxaliplatin could be mimicked by using intracellularly applied 10 mM bis-( o-aminophenoxy)- N,N,N′,N′-tetraacetic acid (BAPTA), known as chelator of calcium ions. We concluded that oxaliplatin was capable of altering the voltage-gated sodium channels through a pathway involving calcium ions probably immobilized by its metabolite oxalate. The medical interest of preventing acute neurotoxic side effects of oxaliplatin by infusing Ca2+and Mg2+is discussed.
Disynaptic Inhibition of Omnipause Neurons Following Electrical Stimulation of the Superior Colliculus in Alert Cats
Authors: Yoshida Kaoru , Iwamoto Yoshiki , Chimoto Sohei , Shimazu Hiroshi
Published: December 2017

We investigated the synaptic organization responsible for the inhibition of omnipause neurons (OPNs) following stimulation of the superior colliculus (SC) in alert cats. Stimulation electrodes were implanted bilaterally in the rostral and caudal SC where a short-pulse train induced small and large saccades, respectively. Effects of single-pulse stimulation on OPNs were examined with intracellular and extracellular recordings. In contrast to monosynaptic excitatory postsynaptic potentials, which were induced by rostral SC stimulation, inhibitory postsynaptic potentials were induced with disynaptic latencies (1.3–1.9 ms) from both the rostral and caudal SC in most OPNs. Analysis of a larger extracellular sample complemented intracellular observations. Monosynaptic activation of OPNs was elicited more frequently from rostral sites than from caudal sites, whereas spike suppression with disynaptic latencies was induced by caudal as well as rostral stimulation with similar frequencies. The results imply that disynaptic inhibition is produced by activation of SC cells that are distributed over wide regions related to saccades of different sizes. We suggest that signals from these neurons initiate a saccadic pause of OPNs through single inhibitory interneurons.
Network Activity Evoked by Neocortical Stimulation in Area 36 of the Guinea Pig Perirhinal Cortex
Authors: Biella Gerardo , Uva Laura , de Curtis Marco
Published: December 2017

The perirhinal cortex is a key structure involved in memory consolidation and retrieval. In spite of the extensive anatomical studies that describe the intrinsic and extrinsic associative connections of the perirhinal cortex, the activity generated within such a network has been poorly investigated. We describe here the pattern of synaptic interactions that subtend the responses evoked in area 36 of the perirhinal cortex by neocortical and local stimulation. The experiments were carried out in the in vitro isolated guinea pig brain. The synaptic perirhinal circuit was reconstructed by integrating results obtained during intracellular recordings from layer II–III neurons with simultaneous current source density analysis of laminar profiles performed with 16-channel silicon probes. Both neocortical and local stimulation of area 36 determined a brief monosynaptic excitatory potential in layer II–III neurons, followed by a biphasic synaptic inhibitory potential possibly mediated by a feed-forward inhibitory circuit at sites close to the stimulation electrode and a late excitatory postsynaptic potential (EPSP) that propagated at distance within area 36 along the rhinal sulcus. During a paired-pulse stimulation test, the inhibitory postsynaptic potential (IPSP) and the late EPSP were abolished in the second conditioned response, suggesting that they are generated by poli-synaptic circuits. Current source density analysis of the field responses demonstrated that 1) the monosynaptic activity was generated in layers II–III and 2) the sink associated to the disynaptic responses was localized within the superficial layer of area 36. We conclude that the neocortical input induces a brief monosynaptic excitation in area 36 of the perirhinal cortex, that is curtailed by a prominent inhibition and generates a recurrent excitatory associative response that travels at distance within area 36 itself. The results suggest that the perirhinal cortex network has the potentials to integrate multimodal incoming neocortical information on its way to the hippocampus.
Listening Through Different Ears Alters Spatial Response Fields in Ferret Primary Auditory Cortex
Authors: Mrsic-Flogel Thomas D. , King Andrew J. , Jenison Rick L. , Schnupp Jan W. H.
Published: December 2017

The localization of sounds in space is based on spatial cues that arise from the acoustical properties of the head and external ears. Individual differences in localization cue values result from variability in the shape and dimensions of these structures. We have mapped spatial response fields of high-frequency neurons in ferret primary auditory cortex using virtual sound sources based either on the animal's own ears or on the ears of other subjects. For 73% of units, the response fields measured using the animals' own ears differed significantly in shape and/or position from those obtained using spatial cues from another ferret. The observed changes correlated with individual differences in the acoustics. These data are consistent with previous reports showing that humans localize less accurately when listening to virtual sounds from other individuals. Together these findings support the notion that neural mechanisms underlying auditory space perception are calibrated by experience to the properties of the individual.
Sonometric Measurements of Motor-Neuron-Evoked Movements of an Internal Feeding Structure (the Radula) in Aplysia
Authors: Orekhova Irina V. , Jing Jian , Brezina Vladimir , DiCaprio Ralph A. , Weiss Klaudiusz R. , Cropper Elizabeth C.
Published: December 2017

In many systems used to study rhythmic motor programs, the structures that generate behavior are at least partially internal. In these systems, it is often difficult to directly monitor neurally evoked movements. As a consequence, although motor programs are relatively well characterized, it is generally less clear how neural activity is translated into functional movements. This is the case for the feeding system of the mollusk Aplysia. Here we used sonomicrometry to monitor neurally evoked movements of the food-grasping organ in Aplysia, the radula. Movements were evoked by intracellular stimulation of motor neurons that innervate radula muscles that have been extensively studied in reduced preparations. Nevertheless our results indicate that the movements and neural control of the radula are more complex than has been assumed. We demonstrate that motor neurons previously characterized as radula openers (B48) and closers (B8, B15, B16) additionally produce other movements. Moreover, we show that the size of the movement evoked by a motor neuron can depend on the preexisting state of the radula. Specifically, the motor neurons B15 and B16 produce large closing movements when the radula is partially open but produce relatively weak closing movements in a preparation at rest. Thus the efficacy of B15 and B16 as radula closers is context dependent.
AMPA and NMDA Receptors Regulate Responses of Neurons in the Rat's Inferior Colliculus
Authors: Zhang Huiming , Kelly Jack B.
Published: December 2017

The contribution of N-methyl-d-aspartate (NMDA) and AMPA receptors to auditory responses in the rat's inferior colliculus was examined by recording single-unit activity before, during, and after local iontophoretic application of receptor-specific antagonists. Tone bursts and sinusoidal amplitude modulated sounds were presented to one ear, and recordings were made from the contralateral central nucleus of inferior colliculus (ICC). The receptor specific antagonists, (±)-3-(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP) for NMDA receptors and 1,2,3,4-tetrahydro-6-nitro-2,3-dioxo-benzo[f]quinoxaline-7-sulfonamide (NBQX) for AMPA receptors, were released at the recording site through a multi-barreled pipette. For most neurons, either CPP or NBQX alone resulted in a reversible reduction in the number of action potentials evoked by tonal stimulation. For neurons with an onset response pattern, NBQX either completely eliminated or greatly reduced the number of action potentials. CPP also reduced the number of action potentials but had a less pronounced effect than NBQX. For neurons with a sustained firing pattern, NBQX reduced the total number of action potentials, but had a preferential effect on the early part (first 10–20 ms) of the response. CPP also resulted in a reduction in the total number of action potentials, but had a more pronounced effect on the later part (>20 ms) of the response. These results indicate that both AMPA and NMDA receptors contribute to sound evoked excitatory responses in the ICC. They have a selective influence on early and late components of tone-evoked responses. Both receptor types are involved in generating excitatory responses across a wide range of sound pressure levels as indicated by rate level functions obtained before and during drug application. In addition, both CPP and NBQX reduced responses to sinusoidal amplitude modulated sounds. The synchrony of firing to the modulation envelope as measured by vector strength at different rates of modulation was not greatly affected by either CPP or NBQX in spite of the decrease in firing rate.
Synaptic Noise Improves Detection of Subthreshold Signals in Hippocampal CA1 Neurons
Authors: Stacey William C. , Durand Dominique M.
Published: December 2017

Stochastic resonance (SR) is a phenomenon whereby the detection of a low-level signal is enhanced in a nonlinear system by the introduction of noise. Studies of the effects of SR in neurons have suggested that noise could play a prominent role in improving detection of small signals. Most experimental SR research has focused on the role of noise in sensory neurons using physiological stimuli. Computer simulations show that signal detection in hippocampal neurons is improved by the addition of physiological levels of noise applied extracellularly to synaptic inputs. These results were confirmed experimentally. We now report that endogenous noise sources can also improve signal detection. The noise source was generated by modulating the random synaptic activity on the apical dendrites of CA1 cells in rat hippocampal slices using subthreshold cathodic current. Intracellular recordings of CA1 cells showed that even small increases of synaptic noise are able to greatly improve the detection of an independent, synaptic, subthreshold stimulus as predicted by the simulations. The noise variance in the CA1 cell was compared with the resting variance and with variance changes caused by several endogenous noise sources. In all cases, the increased noise variance was well within the physiological range. These results were supplemented and analyzed with a CA1 computer model. The improved signal detection with small amounts of endogenous noise suggests that the diverse inputs to CA1 are able to improve detection of subthreshold synaptic signals and could provide a means to modulate detection of specific inputs in the hippocampus.
Dopamine D4 Receptor Activation Inhibits Presynaptically Glutamatergic Neurotransmission in the Rat Supraoptic Nucleus
Authors: Price Christopher J. , Pittman Quentin J.
Published: December 2017

Oxytocin and vasopressin release from magnocellular neurons of the supraoptic nucleus is under the control of glutamate-dependent excitation. The supraoptic nucleus also receives a generalized dopaminergic input from hypothalamic sources. To determine if dopamine can influence this excitatory drive onto the magnocellular neurons, we used whole-cell patch clamp to record the effect of dopamine on evoked and miniature excitatory postsynaptic currents in rat hypothalamic slices. Dopamine exposure (30 μM to 1 mM) induced a large and reversible reduction in the amplitude of evoked excitatory postsynaptic current in nearly all magnocellular cells tested. D4 receptors appeared to mediate dopamine's activity, based on inhibition of the response with 50 μM clozapine, but not by SCH 23390 or sulpiride, and mimicry of dopamine's action with the D4 specific agonist, PD 168077. Analysis of paired-pulse experiments and miniature postsynaptic currents indicated that dopamine's action involved a presynaptic mechanism, since the frequency of miniature postsynaptic currents was reduced with dopamine exposure without any change in current kinetics or amplitude, while the paired-pulse ratio increased. We therefore have demonstrated for the first time a role for dopamine D4 receptors in the supraoptic nucleus in the presynaptic inhibition of glutamatergic neurotransmission onto magnocellular neurons.