bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of furosemide on distortion product otoacoustic emissions and on neuronal responses in the anteroventral cochlear nucleus
Authors: Rubsamen R. , Mills D. M. , Rubel E. W.
Published: December 2017

1. The objective of this study was to precisely evaluate the relationship between the threshold of neurons in the anteroventral cochlear nucleus (AVCN) and the properties of distortion product otoacoustic emissions (DPOAEs). Response areas of multiunit clusters in the AVCN and DPOAEs in the ear canal were measured alternately in the adult gerbil during furosemide-induced changes of the endocochlear potential. Stimulus frequencies of the probe tones for DPOAE measurement were in the range of f1 = 1.7-7.6 kHz and f2 = 2.0-9.0 kHz; the ratio f2:f1 was always 1.18. Stimulus amplitudes were varied in 5-dB steps from 30 to 80 dB SPL, with either equal amplitudes (L1 = L2) or unequal, with L1 set 10 dB above L2. Multiunit response areas were determined from cluster responses to a series of 100-ms tone bursts presented with a pseudo-random sequence in frequency and intensity. 2. Changes in the multiunit discharge properties after 50-75 mg/kg furosemide injection were as follows: the best frequency (BF) threshold increased from initial values in the range of 20-30 dB SPL to 50-80 dB SPL at 10-20 min postinjection and then recovered fully by 60-90 min. The spontaneous discharge activity decreased to zero before any changes in the frequency threshold curve were observed and did not return to initial values for several hours. Likewise, total discharge rates of stimulus elicited responses were reduced and tended to stay reduced even after BF threshold had fully recovered. 3. From the DPOAE measurements, the changes observed in the cubic distortion tone (CDT, 2f1-f2) emission after furosemide injection were as follows: at high levels of the probe tones, changes in the emission intensities generally stayed within a 10-dB range. The CDT amplitudes for low stimulus levels, however, were typically reduced by up to 40 dB, but recovered (depending on the furosemide dosage) by approximately 60-90 min. 4. At low to moderate stimulus levels of 40-60 dB SPL, there was a near perfect, minute-by-minute covariation of the ear canal CDT amplitude and the BF threshold measured in the AVCN. A 10-dB increase in threshold was associated with a 5- to 7-dB decrease in the CDT emission. 5. The optimum stimulus parameter set for the noninvasive estimation of cochlear performance from the CDT response was for stimulus amplitudes L1 = 50, L2 = 40 dB SPL. 6. This experiment demonstrates that CDT emissions at low stimulus levels are very good predictors of the thresholds of cochlear afferents, but this validity is lost for BF thresholds greater than approximately 60-70 dB SPL. 7. The ear canal CDT amplitude is better correlated with the BF threshold sensitivity of neuronal response areas in the AVCN than with the spontaneous discharge rate or absolute above-threshold discharge rates.
Frequency-dependent depression of excitatory synaptic transmission is independent of activation of MCPG-sensitive presynaptic metabotropic glutamate receptors in cultured hippocampal neurons
Authors: Maki R. , Cummings D. D. , Dichter M. A.
Published: December 2017

1. A paired-pulse paradigm, and a high-frequency train followed by a test pulse, were used to investigate the possible role of presynaptic metabotropic glutamate receptors (mGluRs) in frequency-dependent modulation of the amplitude of excitatory post-synaptic currents (EPSCs). Paired whole cell patch-clamp recordings from monosynaptically connected hippocampal neurons maintained in very low-density cultures were performed, using the mGluR antagonist (RS)-alpha-methyl-4-carboxyphenylglycine (MCPG, 500 microM) and the mGluR agonist (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid [(1S,3R)-ACPD, 100 microM]. 2. Paired-pulse depression (PPD) was observed in all the excitatory pairs recorded. The average PPD ratio (amplitude of the 2nd EPSC divided by the amplitude of the 1st EPSC) was 0.80 +/- 0.1 (SD) (n = 8). Application of the mGluR antagonist MCPG had no effect on the amplitude of the EPSCs and did not affect the ratio of the two EPSCs (PPD ratio 0.79 +/- 0.2). 3. The amplitudes of 10 successive EPSCs stimulated at a high frequency (20 Hz) decremented on average in both 4 mM extracellular Ca2+ (n = 5) and in 1 mM extracellular Ca2+ (n = 6). In all pairs tested, posttetanic depression (PTD) was observed (PTD ratio 0.7 +/- 0.2). Bath application of MCPG (500 microM) did not affect the amplitudes of the EPSCs during the train; MCPG also did not affect PTD. 4. The mGluR agonist (1S,3R)-ACPD depressed the amplitudes of the EPSCs in both the paired-pulse (1st EPSC, 35 +/- 9%; 2nd EPSC, 36 +/- 10%) and posttetanic pulse (1 and 4 mM extracellular Ca2+) paradigms. The amount of depression observed, both PPD and PTD, remained unaffected by application of (1S,3R)-ACPD. Coapplication of the antagonist MCPG (500 microM) blocked the effects of (1S,3R)-ACPD (100 microM). 5. We conclude that frequency-dependent depression of EPSC amplitudes occurs independent of endogenous activation of MCPG-sensitive mGluRs in cultured hippocampal neurons. Moreover, we demonstrate that exogenous activation of mGluRs by the agonist (1S,3R)-ACPD can produce additional EPSC depression above that already present due to frequency-dependent mechanisms.
Properties of channels mediating the apamin-insensitive afterhyperpolarization in vagal motoneurons
Authors: Sah P.
Published: December 2017

1. Whole cell recordings were obtained from neurons of the dorsal motor nucleus of the vagus in transverse slices of guinea pig medulla. From a holding potential of -40 mV, short depolarizing voltage steps activated two calcium-dependent potassium currents, Gk(Ca),1 and Gk(Ca),2. 2. Gk(Ca),1 was completely blocked by apamin (100 nM). Gk(Ca),2 was apamin insensitive, voltage independent, and reversed close to the potassium equilibrium potential. 3. Activation of Gk(Ca),2 was associated with an increase in current variance. The channels underlying the slow component were analyzed by stationary and nonstationary fluctuation analysis. Current variance was linearly related to mean current for small current amplitudes but clearly deviated from linearity near the peak of Gk(Ca),2. The predicted single channel conductance was 6.8 +/- 2.5 (SE) pS. Probability of channel opening rose to at most 0.68. The average number of available Gk(Ca),2 channels on vagal neurons was 4,437 +/- 591. 4. Power spectra were constructed from the peak current. Spectra were well fitted with a single Lorentzian with a corner frequency of 72 +/- 7 Hz. The mean burst duration of the channels was 3.8 +/- 0.5 ms. These results indicate that a new type of calcium-activated channel underlies Gk(Ca),2.
Motor adaptation to Coriolis force perturbations of reaching movements: endpoint but not trajectory adaptation transfers to the nonexposed arm
Authors: Dizio P. , Lackner J. R.
Published: December 2017

1. Reaching movements made in a rotating room generate Coriolis forces that are directly proportional to the cross product of the room's angular velocity and the arm's linear velocity. Such Coriolis forces are inertial forces not involving mechanical contact with the arm. 2. We measured the trajectories of arm movements made in darkness to a visual target that was extinguished at the onset of each reach. Prerotation subjects pointed with both the right and left arms in alternating sets of eight movements. During rotation at 10 rpm, the subjects reached only with the right arm. Postrotation, the subjects pointed with the left and right arms, starting with the left, in alternating sets of eight movements. 3. The initial perrotary reaching movements of the right arm were highly deviated both in movement path and endpoint relative to the prerotation reaches of the right arm. With additional movements, subjects rapidly regained straight movement paths and accurate endpoints despite the absence of visual or tactile feedback about reaching accuracy. The initial postrotation reaches of the left arm followed straight paths to the wrong endpoint. The initial postrotation reaches of the right arm had paths with mirror image curvature to the initial perrotation reaches of the right arm but went to the correct endpoint. 4. These observations are inconsistent with current equilibrium point models of movement control. Such theories predict accurate reaches under our experimental conditions. Our observations further show independent implementation of movement and posture, as evidenced by transfer of endpoint adaptation to the nonexposed arm without transfer of path adaptation. Endpoint control may occur at a relatively central stage that represents general constraints such as gravitoinertial force background or egocentric direction relative to both arms, and control of path may occur at a more peripheral stage that represents moments of inertia and muscle dynamics unique to each limb. 5. Endpoint and path adaptation occur despite the absence both of mechanical contact cues about the perturbing force and visual or tactile cues about movement accuracy. These findings point to the importance of muscle spindle signals, monitoring of motor commands, and possibly joint and tendon receptors in a detailed trajectory monitoring process. Muscle spindle primary and secondary afferent signals may differentially influence adaptation of movement shape and endpoint, respectively.
Nitric oxide mediates the inhibitory effects of SDPNFLRFamide, a nematode FMRFamide-related neuropeptide, in Ascaris suum
Authors: Bowman J. W. , Winterrowd C. A. , Friedman A. R. , Thompson D. P. , Klein R. D. , Davis J. P. , Maule A. G. , Blair K. L. , Geary T. G.
Published: December 2017

1. The physiological effects of two Phe-Met-Arg-Phe-NH2 (FMRFamide)-related neuropeptides isolated from the free-living nematode Panagrellus redivivus, SDPNFLRFamide (PF1) and SADPNFLRFamide (PF2), were examined using neuromuscular preparations from the parasitic nematode Ascaris suum. 2. PF1 and PF2 hyperpolarized muscle membrane and induced sustained flaccid paralysis, independent of external Cl-, in both innervated and denervated preparations. 3. PF1 reversed spastic contractions induced by the cholinomimetic levamisole, elevated K+, or the excitatory nematode FMRFamide-related neuropeptides KNEFIRFamide or KHEYLRFamide. 4. PF1 reversal of levamisole contraction was blocked by pretreatment with agents that interfere with nitric oxide (NO) synthesis (e.g., N-nitro-L-arginine), whereas sodium nitroprusside, which releases NO in solution, mimicked PF1 and PF2. 5. NO synthase activity, monitored by the conversion of [3H]arginine to [3H]citrulline, was twice as abundant in A. suum hypodermis as in muscle, but was not present in reproductive tissue. The relative abundance of NO synthase activity in these tissues was similar to the observed specific binding of [3H]PF1. 6. These results suggest that the inhibitory effects of PF1 and PF2 on nematode somatic muscle are mediated by NO, and that the hypodermis may serve a role in this process analogous to that of the endothelium in vertebrate vasculature.
Slow and fast synaptic inhibition evoked by pattern-generating neurons of the gastric mill network in spiny lobsters
Authors: Elson R. C. , Selverston A. I.
Published: December 2017

1. In this paper we begin an assessment of the role of synaptic properties, especially synaptic time course, in the function of the central pattern generator circuit (CPG) that controls rhythmic movements of the gastric mill in the foregut of spiny lobster (Panulirus interruptus). 2. The majority of neurons in the gastric CPG are motor neurons (MNs) that innervate striated muscles of the gastric mill but that also make electrical and inhibitory chemical interconnections within the neuropil of the stomatogastric ganglion. We studied the ionic dependence, pharmacology, and time course of inhibitory postsynaptic potentials (IPSPs) evoked by two such MNs, the dorsal gastric (DG) and lateral gastric (LG), in their central synaptic partners. In the periphery, LG and DG are thought to release glutamate. 3. LG and DG evoke two types of IPSPs in follower neurons. The first, fast type of IPSP rises rapidly (the graded component within 100-300 ms, the spike-mediated components within a few tens of ms), is mediated by increased chloride and potassium conductances, and is blocked by < or = 10 microM picrotoxin (PTX). These fast IPSPs closely resemble the glutamatergic IPSPs described in the pyloric circuit of the same ganglion. 4. The second, slow type of IPSP has a long rise time (1-2 s), is mediated by increased conductance to potassium (with little or no involvement of chloride), and is not blocked by 10 microM PTX, 5 mM tetraethylammonium chloride, or 0.1 mM scopolamine. These properties distinguish slow IPSPs from the forms of glutamatergic and cholinergic inhibition that have been described in the pyloric circuit. 5. Fast inhibition occurs alone at connections from DG and LG to power stroke MNs (median gastric and gastric mill). Slow inhibition occurs in parallel with fast inhibition (producing dual-component responses) at connections from LG to return stroke neurons [lateral posterior gastric MNs, (LPGs) and interneuron 1]. DG seems to evoke only a slow IPSP in LPGs. 6. The transmitter mediating the fast IPSPs is likely to be glutamate. We discuss possible mechanisms for the slow IPSP but have no evidence at present concerning the transmitter(s) involved. Slow inhibition is likely to be an important synaptic "building block" in the gastric CPG; it is "tuned" to the duration of gastric bursts and may contribute to the long cycle period of gastric rhythms.
Relationship between changes of glomus cell current and neural response of rat carotid body
Authors: Cheng P. M. , Donnelly D. F.
Published: December 2017

1. Mature rat carotid bodies were harvested and sinus nerve activity was recorded in vitro during superfusion with Ringer saline. Membrane currents of glomus cells were simultaneously recorded using conventional whole cell or perforated-patch whole cell recording. Presumptive glomus cells were identified by the presence of a rapidly activated, voltage-dependent outward current above a threshold of -20 mV. 2. Outward current of presumptive glomus cells was inhibited by tetraethylammonium chloride (TEA) (20 mM) and by verapamil (5-10 microM), consistent with previous studies in which isolated glomus cells were used. Somal capacitance, calculated from the current transient following a step hyperpolarization, was 7.47 +/- 0.54 (SE) pF (n = 52). Membrane resistance for perforated-patch recordings was 820 +/- 187 M omega. 3. In perforated-patch recordings, brief periods of hypoxia (30-45 s) caused a marked increase in nerve activity to 21.6 +/- 2.7 times baseline spiking frequency (n = 59) but no significant change in membrane resistance or outward current. No change in holding current was detected, although the low amplifier gain precluded high-resolution measurement. Similar results were obtained using conventional whole cell recording, except that outward current significantly decreased during hypoxia but failed to recover in the immediate posthypoxia period. 4. TEA (20 mM) rapidly inhibited outward current to 55 +/- 7% (n = 15) of predrug current, but nerve activity only slightly increased to 2.0 +/- 0.3 times baseline spike frequency (n = 15). Brief anoxia (40 s in duration) in the presence of TEA evoked a brisk increase in nerve activity to 30 +/- 13 times baseline frequency (n = 3), demonstrating that organ function was not blocked by TEA. 5. Charybdotoxin (10 nM) significantly reduced outward current by 12.1 +/- 3.0% (n = 11) but did not significantly alter nerve activity, holding current, or membrane resistance. Apamin (100 nM) did not significantly affect nerve activity, membrane resistance, or holding current. Outward current decreased by 11.4 +/- 6.1% (n = 13). 6. These results show a dissociation between changes in glomus cell voltage-gated outward currents and changes in afferent nerve activity. This suggests that modulation of glomus cell K+ current by hypoxia is not the primary step in initiating the nerve response to hypoxia in the rat carotid body.
Lateralization of prefrontal activation during internal mental calculation: a functional magnetic resonance imaging study
Authors: Burbaud P. , Degreze P. , Lafon P. , Franconi J. M. , Bouligand B. , Bioulac B. , Caille J. M. , Allard M.
Published: December 2017

1. Functional magnetic resonance imaging (fMRI) at 1.5 T was used to investigate the lateralization of prefrontal cortex activity during internal mental calculation in 16 human volunteers (8 right-handed and 8 left-handed). Subjects were asked to perform two different tasks: 1) a serial subtraction of prime numbers and 2) a control task in which they mentally recited numbers. 2. Signal modifications were regularly observed in the prefrontal cortex (Brodmann's area 46) during the serial subtraction of prime numbers, whereas the number listing task poorly activated the same areas. 3. In right-handed subjects, activation was clearly lateralized in the left dorsolateral prefrontal cortex, whereas a frequent bilateral activation was found in left-handed subjects. 4. We conclude that prefrontal activation during mental calculation is lateralized in a manner similar to that reported during linguistic tasks, i.e., a clear lateralization in right- but not in left-handed subjects.
Unexpected motor patterns for hindlimb muscles during slope walking in the cat
Authors: Smith J. L. , Carlson-Kuhta P.
Published: December 2017

1. Hindlimb kinematics and motor patterns were assessed from high-speed cine film synchronized with electromyographic (EMG) data from cats trained to walk on a walkway placed at four grades (25, 50, 75, and 100%). 2. Flexor muscles of the hip (iliopsoas) and ankle (tibialis anterior) had similar activity patterns for the swing phase of up- and down-slope walking; both flexor muscles also had stance-related activity during down-slope walking and this was unexpected. Extensor muscles of the hip (anterior biceps femoris and anterior semimembranosus), knee [vastus lateralis (VL)], and ankle [lateral gastrocnemius (LG)] were active during the stance phase of up-slope walking. The VL and LG activity was reduced in duration during stance of down-slope walking and centered around paw contact. Hip extensors, however, were totally inactive during stance of down-slope walking, and this was not expected. 3. Flexor muscles at the hip and ankle (not extensor muscles) dominated the stance phase of down-slope walking, especially at the steeper slopes. This switch in motor patterns may be required to counterbalance external forces that produced extension at the hip and ankle joints during the stance phase of down-slope walking. Neural mechanisms for programming stance-related activity of flexor muscles are discussed.
Amplification of synaptic current by persistent sodium conductance in apical dendrite of neocortical neurons
Authors: Schwindt P. C. , Crill W. E.
Published: December 2017

1. Evidence for amplification of synaptic current by voltage-gated channels in dendrites of neocortical pyramidal neurons was demonstrated by examining the effect of specific channel blocking agents on the current arriving at the soma during iontophoresis of glutamate at a distal site on the apical dendrite. 2. Dendritic noninactivating Na+ channels were implicated in this voltage-dependent amplification of the transmitted current because it was maintained for > 1 s and because tetrodotoxin (TTX) eliminated much of this amplification. 3. Specific blockers of N-methyl-D-aspartate (NMDA) glutamate receptors reduced the amplitude of the glutamate-evoked current at all potentials and also reduced the non-TTX-sensitive component of voltage-dependent augmentation. The effects of TTX were identical whether or not NMDA channels were blocked. 4. We conclude that a persistent Na+ conductance exists in the apical dendrite of neocortical neurons. Together with the NMDA conductance at the synaptic site it provides a mechanism for the graded, voltage-dependent amplification of tonic, excitatory synaptic input. This amplification results in much more effective transmission of tonic excitatory current to the soma than would occur in a passive dendrite.
Neurotransmitters acting via different G proteins inhibit N-type calcium current by an identical mechanism in rat sympathetic neurons
Authors: Ehrlich I. , Elmslie K. S.
Published: December 2017

1. We studied the mechanism of voltage-dependent inhibition of N-type calcium current by norepinephrine (NE) and vasoactive intestinal peptide (VIP) in adult rat superior cervical ganglion (SCG) neurons using the whole cell patch-clamp technique. 2. The voltage dependence of inhibition is manifest in the reversal of inhibition by strong depolarization. We tested the hypothesis that this voltage dependence results from disruption of G proteins binding to calcium channels. According to this hypothesis, the kinetics of calcium current reinhibition following a strong depolarization should become faster for higher concentrations of active G proteins. 3. Assuming that larger inhibitions result from higher concentrations of active G proteins, we used different concentrations of NE to alter the amplitude of inhibition and, thus, the active G protein concentration. We found that the kinetics of reinhibition at -80 mV following a depolarizing pulse to +80 mV were faster for larger inhibitions. 4. VIP induces voltage-dependent inhibition of N-current via a different G protein (Gs) than that of NE (Go). We found that the effect of VIP on reinhibition kinetics was identical to that produced by NE. 5. Combined application of NE and VIP did not greatly increase the amplitude of the inhibition but significantly increased the rate of reinhibition. Thus NE plus VIP appear to greatly increase the concentration of the molecule binding to the channel (G protein according to the hypothesis). 6. The kinetics of calcium current disinhibition during strong depolarization (step to +80 mV) did not change with the size of the inhibition induced by NE, VIP or application of NE and VIP together. 7. Both the concentration-dependent reinhibition kinetics and concentration-independent disinhibition kinetics are consistent with the hypothesis that active G proteins bind directly to N-type calcium channels to modulate their activity in rat sympathetic neurons.
Morphology of functional long-ranging primary afferent projections in the cat spinal cord
Authors: Koerber H. R. , Mirnics K.
Published: December 2017

1. A beta-cutaneous primary afferent fibers were impaled in the dorsal columns of alpha-chloralose-anesthetized cats. Penetrations were made with the use of electrodes filled with 2 or 5% N-(2-aminoethyl) biotinamide hydrochloride (Neurobiotin, NB) in 0.1 or 1 M KCl. After determining its adequate stimulus, each fiber was activated by current pulses (18 Hz) injected via the microelectrode. The resulting cord dorsum potential (CDP) was recorded at four locations. NB was then injected into the fiber with the use of positive current pulses (11-22 nA) and a 75% duty cycle. 2. After allowing 2-8 h for diffusion, animals were perfused with saline (37 degrees C) followed by 4% paraformaldehyde (4 degrees C). Frozen 50-microns sections were cut in either the transverse or sagittal plane, processed on slides with the use of standard avidin-biotin protocols, and visualized by the nickel-enhanced diaminobenzidine (DAB) reaction. 3. A total of 15 A beta-cutaneous afferents innervating both rapidly (RA) and slowly adapting (SA) receptors were adequately stained and their central projections recovered. For selected fibers the rostrocaudal and laminar bouton distributions were determined and compared with the distribution of monosynaptic CDP amplitudes recorded at the four surface locations. 4. The rostrocaudal extent of a single A beta-afferent fiber bouton distribution visualized with NB ranged from 8 to 17.5 mm (14.4 +/- 2.4 mm, mean +/- SD), or two to three times greater than that previously shown with the use of horseradish peroxidase (HRP). 5. The strong correlation between the rostrocaudal distribution of boutons and monosynaptic CDP amplitudes, and the improved agreement between modeled and observed CDP amplitudes over that seen previously with the use of HRP (mean percent error, HRP = 23 +/- 2.9%; NB = 9 +/- 2.3%), suggest that boutons along the entire length of the visualized distribution contribute to the recorded potentials. 6. Taken together, these findings suggest that inputs from a given point on the skin can directly influence sensory information processing over a much greater rostrocaudal extent than predicted by dorsal horn somatotopic maps. These findings are discussed in terms of their implications for spinal cord plasticity.
Expression of LTP by AMPA and/or NMDA receptors is determined by the extent of NMDA receptors activation during the tetanus
Authors: Aniksztejn L. , Ben-Ari Y.
Published: December 2017

1. We have tested, in CA1 hippocampal slices, the hypothesis that the expression of long-term potentiation (LTP) by alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and/or N-methyl-D-aspartate (NMDA) receptors depends on the degree of NMDA receptors activation during the tetanus. 2. Slices were perfused in an artificial cerebrospinal fluid (ACSF) containing glycine (1 microM), bicuculline (5 microM) and a low Mg2+ concentration (0.3 mM). To measure the AMPA and NMDA receptor-mediated field excitatory postsynaptic potential (fEPSPA and fEPSPN, respectively), we have used the following procedure: control fEPSPA was first measured, 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 10 microM) was then added, and fEPSPN was evoked. CNQX was washed, and once control fEPSPA was recorded, the Schaffer collaterals were tetanized at a weak or a strong intensity. The slope of fEPSPA was measured for 30-45 min followed by that of fEPSPN after the application of CNQX. 3. At a weak intensity (TW, which corresponds to a fEPSPA of approximately 0.3 mV of amplitude and no fEPSPN), the tetanic stimulation generated LTP of fEPSPA (58.7 +/- 8.1% mean +/- SE, n = 9) but no significant potentiation of the fEPSPN (11.2 +/- 2.2%, n = 9). These values were significantly different (P < 0.05, analysis of variance, Fisher test). 4. In 9 of 13 slices, tetanic stimulation of strong intensity (Ts, intensity corresponding to a fEPSPN of approximately 0.3 mV of amplitude) generated LTP of fEPSPN (89.1 +/- 17.2%) but not of fEPSPA (9.44 +/- 2.8%). In the four remaining slices the tetani induce LTP of both fEPSPA and fEPSPN (81.7 +/- 14.7% and 101 +/- 35.6%, respectively, both values were not significantly different). 5. We then examined the effects of decreasing fEPSPN by 50% in LTP generated by Ts and Tw. In the presence of 7-Chlorokynurenate (7Cl(-)-Kyn; 6 microM; n = 6), an antagonist of the allosteric glycine site of the NMDA receptors, Ts generated LTP of fEPSPA (63.2 +/- 8.2%) but not of fEPSPN (12.6 +/- 4.0%). Both values were significantly different. Tw still evoked LTP of fEPSPA but of smaller magnitude (29.8 +/- 6.3%, n = 8) than the one obtained in the absence of the antagonist (58.7 +/- 8.1%). Both values were significantly different. 6. The present observation suggests that l) LTP of fEPSPA has a lower threshold than that of fEPSPN, i.e., stronger activation of NMDA receptors during the tetani is required to induce LTP of fEPSPN than the one required for inducing LTP of fEPSPA; and 2) there is a bell-shaped relationship between the degree of activation of NMDA receptors during the tetani and the magnitude of LTP of the fEPSPA: tetani that generate LTP of fEPSPN have a low probability to induce LTP of fEPSPA. We suggest that AMPA and NMDA components are potentiated through two different presumably postsynaptic processes.
Intracellular recordings from intramural neurons in the guinea pig urinary bladder
Authors: Hanani M. , Maudlej N.
Published: December 2017

1. Intracellular recordings were made from intramural neurons in the urinary bladder of guinea pigs. 2. The neurons were located in two types of ganglia: those where the cells were densely packed and those where the neurons were loosely packed. Staining of the cells by intracellular injections of markers showed that the cells had between one to three long processes and several short dendrites. 3. The resting potential measured in 230 neurons was -55.20 +/- 0.67 (SE) mV, and the input resistance was 58.37 +/- 1.78 M omega. 4. Injection of depolarizing currents from the recording electrode evoked two types of firing patterns. In 86.2% of the neurons, depolarizing currents evoked a prolonged firing of action potentials (tonic cells). In the rest of the neurons, a depolarization elicited one to three action potentials only (phasic cells). In all the cells tested, the action potentials were reversibly blocked by tetrodotoxin (TTX; 1 microM). In the presence of TTX. Ca2+ spikes were observed in 50% of the cases. 5. Single action potentials were followed by fast hyperpolarizations having mean duration of 92.7 +/- 6.0 ms and amplitude of 13.3 +/- 1.0 mV. In 62.5% of the cells repetitive firing of action potentials was followed by delayed, slow hyperpolarizations (duration 3.8 +/- 0.5 s), which were diminished by the K+ channel blocker 4-aminopyridine and in Ca+2-free high-Mg2+ medium. These results indicate that the prolonged after-spike hyperpolarizations were due to opening of Ca(2+)-induced K+ channels. 6. Electrical stimulation of nerve fiber tracts evoked fast excitatory synaptic potentials that were blocked by the nicotinic receptor antagonist hexamethonium (0.2 mM). Exogenous acetylcholine elicited depolarizations that were also blocked by hexamethonium. Nerve stimulation at frequencies of 0.1 Hz or higher caused strong facilitation of the synaptic potentials. Stimulation at 10-20 Hz did not evoke slow synaptic potentials.
Dopamine modulates the slow Ca(2+)-activated K+ current IAHP via cyclic AMP-dependent protein kinase in hippocampal neurons
Authors: Pedarzani P. , Storm J. F.
Published: December 2017

1. The effects of dopamine on the slow Ca(2+)-dependent K+ current (IAHP; AHP, afterhyperpolarization) and spike frequency adaptation were studied by whole cell voltage-clamp and sharp microelectrode current-clamp recordings in rat CA1 pyramidal neurons in rat hippocampal slices. 2. Dopamine suppressed IAHP in a dose-dependent manner, under whole cell voltage-clamp conditions. Similarly, under current-clamp conditions, dopamine inhibited spike frequency adaptation and suppressed the slow afterhyperpolarization. 3. The effect of dopamine on IAHP was mimicked by a D1 receptor agonist and blocked by dopamine receptor antagonists only in a minority of the cells. 4. Dopamine suppressed IAHP after blocking or desensitizing the beta-adrenergic receptors and, hence, did not act by cross-reacting with this receptor type. 5. The effects of dopamine on IAHP and spike frequency adaptation were suppressed by blocking the adenosine 3',5'-cyclic monophosphate (cAMP)-dependent kinase (PKA) with Rp-cAMPS and, hence, are probably mediated by the activation of this kinase. 6. We conclude that dopamine increases hippocampal neuron excitability, like other monoamine neurotransmitters, by suppressing IAHP and spike frequency adaptation, via cAMP and protein kinase A. The receptor type mediating this effect of dopamine remains to be defined.
Pallidal neuron activity during sequential arm movements
Authors: Mushiake H. , Strick P. L.
Published: December 2017

1. We examined the activity of neurons in the globus pallidus (GP) while monkeys (n = 2) performed sequential pointing movements under two task conditions: visually guided (TRACK task) and remembered (REM task). 2. Almost two-thirds of the task-related neurons in GP (155/236) were considered task dependent because they displayed exclusive or enhanced (greater than +/- 50%) changes in activity for one of the two task conditions. 3. More than 65% of the task-dependent neurons were termed REM neurons because they either displayed changes in activity that occurred only during the REM task or displayed changes that were more pronounced (greater than +/- 50%) during the REM task than during the TRACK task. 4. Nearly half of the REM neurons in GP displayed changes in activity that were limited to a single phase of the REM task (i.e., phase specific). Phase-specific neurons varied in the extent to which their activity depended on the particular sequence of movements performed. Some displayed a change in activity for all of the eight different movement sequences. Others displayed a change in activity during only one of the eight different sequences (i.e., phase and sequence specific). 5. We speculate that an ensemble of GP neurons with phase-specific responses could be used to encode the detailed spatio-temporal characteristics of a sequential movement. In this way, GP neurons would provide part of the neural substrate that solves the "serial order of motor behavior problem".
Block of cyclic nucleotide-gated channels in salamander olfactory receptor neurons by the guanylyl cyclase inhibitor LY83583
Authors: Leinders-Zufall T. , Zufall F.
Published: December 2017

1. Using whole cell voltage-clamp recordings, the guanylyl cyclase inhibitor LY83583 [6-(phenylamino)-5,8-quinolinedione] is shown to act as a potent blocker of cyclic nucleotide-gated (CNG) channels in isolated olfactory receptor neurons (ORNs) of the tiger salamander. 2. Under our experimental conditions, onset of the blockade by LY83583 occurs on the time scale of seconds and is completely reversed upon wash-out of the drug. Dose-response curves reveal a Kd of 1.4 microM (at -60 mV). Other data suggest that LY83583 acts within the CNG channel pore and that the channels must be in an activated state before the drug can exert its effect. 3. It appears that LY83583 can act on both CNG channels and soluble guanylyl cyclase (sGC) and that these two effects can be distinguished by their different recovery behaviors. The LY83583-induced blockade of CNG channels activated directly by guanosine 3',5' cyclic monophosphate (cGMP) is rapidly reversible (with a recovery time constant of approximately 3 s), whereas previous results have shown that no recovery is obtained during minute-long washing periods when the channels are activated indirectly through exogenous carbon monoxide application, which acts as a stimulator of sGC in ORNs. 4. LY83583 appears to be a novel and useful agent in examining neural functions due to CNG channel responses.
Area postrema voltage-activated calcium currents
Authors: Hay M. , Hasser E. M. , Lindsley K. A.
Published: December 2017

1. Calcium currents in rabbit area postrema neurons were studied with the perforated patch-clamp technique. Experimental conditions eliminated Na+ and K+ currents and identified both low- and high-threshold voltage-activated calcium currents. 2. Low-threshold, T-type calcium currents were observed in 64% of the area postrema neurons recorded. This current activated near -60 mV and had an average peak amplitude of -36.2 +/- 5 pA (mean +/- SE) at -40 mV. This current began rapid inactivation near -95 mV, reached half-maximal inactivation at -71 mV and was totally inactivated by -40 mV. 3. A high-threshold transient current was recorded in all area postrema neurons, which consisted of both a transient and sustained component. This current was present at voltages greater than -40 mV and the transient component of this current was responsible for the majority of the total Ca2+ current. 4. Nickel ions (10 microM) effectively reduced both the T-type current and the high-threshold current. Cadmium ions (100 microM) effectively reduced the high-threshold current while having insignificant effects on the low-threshold current. 5. Application of the dihydropyridine antagonist nimodipine (1-10 microM) had no effect on either the low- or high-threshold voltage-activated calcium Ca2+ in area postrema neurons. In addition, application of omega-conotoxin-GVIA (2-10 microM) was also without effect on either the low- or high-threshold voltage-activated Ca2+ current, suggesting that area postrema neurons possess neither L- or N-type voltage-activated Ca2+ currents. 6. Application of omega-conotoxin MVIIC (10 microM) significantly inhibited the peak high-threshold Ca2+ current by 65.4% suggesting that area postrema neurons do possess a omega-conotoxin MVIIC-sensitive high-threshold Ca2+ channel. 7. Arg-vasopressin (150 nM) significantly increased the transient component of the high-threshold Ca2+ current but had little effect on either the low-threshold or the high-threshold sustained component.
Dopaminergic modulation of glutamate-induced excitations of neurons in the neostriatum and nucleus accumbens of awake, unrestrained rats
Authors: Kiyatkin E. A. , Rebec G. V.
Published: December 2017

1. Single-unit recording and iontophoresis were used in awake, unrestrained rats to assess the action of dopamine (DA) and glutamate (GLU) on the spontaneous activity of neurons in the neostriatum and nucleus accumbens. 2. A total of 88 neurons (40 neostriatal and 48 accumbal) was recorded from 7 rats during 13 recording sessions. During quiet rest, spontaneously active neurons discharged at a slow rate and irregular pattern of activity. Accumbal neurons had a significantly faster level of basal activity than neostriatal neurons (modal values of 10.3 vs. 2.1 imp/s, respectively). 3. Neuronal responses to separate applications of DA and GLU (5-80 nA; 15-30 s) were tested on 40 and 76 units (195 and 227 applications), respectively, during the quiet resting period. The effect of prolonged DA iontophoresis (5-80 nA; 2-3 min) on GLU-induced changes in impulse activity was tested on 38 units (72 applications). 4. GLU activated all cells in both structures. This response appeared with a latency of 0.5-4.0 s at different ejection currents (5-40 nA; mean threshold of 22.2 nA) and was highly variable (103-11,520% of basal activity). Response magnitude correlated strongly with the rate of basal activity (r = 0.822). 5. DA inhibited 75% of spontaneously active neostriatal and accumbal cells with a mean threshold of 20.4 nA. In contrast to the GLU excitation, the DA-induced inhibition was relatively weak in magnitude (10-90% of basal activity) and occurred with relatively longer on- and offset latencies than GLU (2-20 s). The inhibitory effect of DA was absent during phasic activations of neuronal activity associated with movement. Two neostriatal neurons responded to DA with a dose-dependent excitation. 6. Prolonged DA iontophoresis altered both basal impulse activity (causing a decrease in 36 of 72 applications and an increase in 4) and the magnitude of the GLU-induced activation (decreasing it in 27 of 72 applications and increasing it in 12). The net result was an overall enhancement of the GLU response relative to the DA-induced change in basal activity (74% of cases). This increase in the GLU response occurred at relatively low DA ejection currents (10-30 nA). It was stronger in the nucleus accumbens than in the neostriatum and was most evident on cells having both a moderate level of basal activity and a relatively small initial response to GLU. When DA was ejected at high currents (> 40 nA) and/or the magnitude of the preceding GLU-induced activation was high (> 800% of basal activity), DA tended to decrease the GLU response. 7. DA appears to exert a slight depression of striatal and accumbal activity, which has the effect of amplifying the phasic activation induced by GLU. Because forebrain DA release occurs in response to behaviorally important stimuli, the DA-induced modulation of the GLU response may play an important role in regulating goal-directed behavior.
Networks with lateral connectivity. I. dynamic properties mediated by the balance of intrinsic excitation and inhibition
Authors: Xing J. , Gerstein G. L.
Published: December 2017

1. We studied the rapid dynamic changes of neuron response properties in the somatosensory cortex by the use of computer simulations. The model consists of three feedforward layers of spiking neurons, corresponding to skin, subcortex, and cortex structures. Measurements and analysis of model activity throughout this work are similar to those used in neurophysiological experiments. 2. The effects of various parameters on response properties of model neurons were investigated. The most important parameters were the lateral excitation and inhibition in the simulated cortical network. 3. The balance between excitation and inhibition is a key factor in determining the stability of the network model. There is a large excitation-inhibition (E-I) parameter region within which the model can stably respond to inputs. 4. The input-output relations and receptive field (RF) sizes of simulated neurons are modifiable by the E-I balance. The shapes of RFs are determined by both feedforward projections and the spatial distribution of lateral connections. 5. We simulated changes in temporal and spatial properties of neurons in response to manipulations that mimic bicuculine methiodide or glutamate application to the cortex. Simulation results agreed well with experimental data, suggesting that cortical transmitter levels play an important role in the dynamic responses of the neural net through their effects on E-I balance. 6. With parameters of the model set to an inhibition-dominant scheme, the model was able to reproduce experimentally observed rapid RF expansions that follow cortical lesion or input denervation. Simulation results also suggested that spontaneous inputs to a sensory system can serve as a source of tonic inhibition in the cortex. 7. We conclude that lateral connections could produce and maintain a cortical network having dynamic properties without the need to invoke synaptic plasticity. Individual neuron properties could be modified by changing the balance of cortical layer excitation and inhibition. In a real brain, this could be achieved either by changing levels of cortical transmitter (gamma-aminobutyric acid. for example) or by changing tonic background input to the cortical network.
Networks with lateral connectivity. II. Development of neuronal grouping and corresponding receptive field changes
Authors: Xing J. , Gerstein G. L.
Published: December 2017

1. Using a three-layered network model defined in the previous paper, we studied the basic features of neurons in the cortical layer while the synaptic strengths of lateral excitatory connections were made modifiable by a Hebbian learning rule and a normalization process. 2. We found that neurons in the cortical layer formed groups through their lateral excitatory connections after the network was trained with sequential random dot stimulations. Neurons within a group connected tightly; neurons in different groups connected weakly. 3. The effects of model parameters and input parameters on the formation of neuronal groups were investigated. Results showed that the average size and rough shapes of groups were mainly determined by the spatial distribution of lateral connections within the cortical layer, irrespective of input parameters and training methods. Thus groups are structure dependent. 4. Lateral inhibition in the network is the only key factor that affects the grouping of neurons. Without an appropriate amount of distant inhibition, group formation does not occur. Group formation is very robust to all other parameters we tested. On the other hand, group locations are very easily disturbed by inputs or changes of parameters, suggesting that such neuronal groups are dynamically maintained. 5. With the development of neuronal groups, neurons can be divided into two response types. TN-1 neurons respond weakly to inputs and have small receptive fields or do not respond at all (silent); TN-II neurons, approximately 30-40% of all, respond strongly to inputs and have large receptive fields. The two types of neurons also differ with respect to response threshold and temporal firing patterns. After groups formed, receptive fields of TN-II neurons within the same group clustered spatially with high overlap, whereas receptive fields of TN-I neurons with detectable responses shifted systematically with the neuron's spatial location. 6. The two types of neurons are homogeneously distributed across the cortical layer. The population of each type of neuron produces a full representation of the input layer with weak or strong responses, respectively. 7. We concluded that neurons in the cortical network naturally assembled into functional groups. Such groups are dynamic and amenable to change by input stimuli. A fraction of neurons (30-40%) within the same group shares a similar receptive field and strongly respond together to stimuli, so that the network has more robust response to inputs. On the other hand, the responses of a large portion (60-70%) of neurons become weak or silent: these neurons are available for other (unknown) functional purposes.
Single-channel properties of a G-protein-coupled inward rectifier potassium channel in brain neurons
Authors: Grigg J. J. , Kozasa T. , Nakajima Y. , Nakajima S.
Published: December 2017

1. In cultured rat locus coeruleus neurons, somatostatin or met-enkephalin induces an inwardly rectifying K+ conductance. This inward rectifier was analyzed at the single-channel level. 2. Using the inside-out patch-clamp, guanosine 5'-triphosphate (GTP) application to the cytoplasmic side in the presence of somatostatin or met-enkephalin in the pipette produced a large increase in channel activity, which disappeared on switching from GTP to guanosine 5'-diphosphate. 3. The unitary conductance was approximately 30 pS at -95 mV with an extracellular K+ concentration of 156 mM and an intracellular K+ concentration of 124 mM at 23 degrees C. The channel showed burst behavior, and the closed time histogram was fit by two exponentials, with the fast time constant being 0.4 ms. The burst time histogram was also fit by two exponentials, with time constants of 0.24 and 2.0 ms (at 10 nM somatostatin). When the somatostatin concentration was changed from 500 to 1 nM, the kinetic behavior of the channel did not change, except that the open probability of the patch was decreased. 4. The current-voltage relation of the unitary channel current showed inward rectification. The reversal potential coincided with the K+ equilibrium potential, and it shifted according to a change in the K+ equilibrium potential. 5. In the presence of external somatostatin, the application of guanosine 5'-O-(3-thiotriphosphate) to the cytoplasmic side induced an irreversible activation of this channel. 6. These results indicate that this K+ channel is the microscopic counterpart of the somatostatin- or met-enkephalin-induced inwardly rectifying K+ current in whole cell recording, and that the channel is activated by a G protein without a diffusible second messenger. Thus this channel is identified as a neuronal G-protein-coupled inward rectifier K+ channel. 7. Analysis of the burst behavior, based on a close-close-open kinetic model, revealed that there are at least four states in the K+ channel, a short gap, a longer closing, a short opening, and a long opening, and that the neuronal inward rectifier is activated at faster rates than the atrial inward rectifier.