bluuebunny/crossref_metadata_2025 huggingface dataset:
A molecular model of low-voltage-activated calcium conductance
Authors: Miller A. , Hu B.
Published: December 2017

1. T-type or low-voltage-activated Ca2+ channels (IT) expressed in the mammalian thalamus play an important physiological role in the induction of membrane potential oscillations and in the regulation of the timing of synaptic signaling. On the basis of recent molecular studies on Ca2+, Na+, and K+ channels, a structure-kinetic model has been proposed for IT. 2. The model considers that the pore-opening process of IT is governed by three of the four protein domains that are arranged asymmetrically across the membrane plane. The three cytoplasmic linkers connecting individual channel domains serve as inactivation gates. On a membrane voltage change, each domain may engage independently into a sequential, thermodynamically coupled conformational change, thereby causing channel activation and inactivation. 3. A linear Marcov chain reaction with coupled channel activation and inactivation was adopted to test the kinetic feasibility of this trimeric model in a single-compartmental thalamic cell. The differential equations for voltage-dependent rate constants and transitional rates were solved to produce macroscopic T-type Ca2+ current. 4. Our simulation results indicate that this novel structure-kinetic model produces excellent predictions of the macroscopic behaviors of IT, and, more importantly, it provides some new insights into the microscopic mechanism underlying channel recovery.
Electrical stimulation in forebrain nuclei elicits learned vocal patterns in songbirds
Authors: Vicario D. S. , Simpson H. B.
Published: December 2017

1. Microstimulation (trains of biphasic current pulses at 50-400 Hz lasting 2-4 s) was delivered unilaterally to known vocal control areas in the brains of zebra finches and canaries to elicit vocalizations. 2. Simple vocalizations were elicited from the midbrain, and the lowest thresholds were obtained from the dorsomedial nucleus of the intercollicular complex (DM). 3. Vocalizations elicited from forebrain vocal control nuclei higher vocal center (HVC) and robustus archistriatalis (RA) were complex, with features specific not only to the species, but to the individual bird's own learned song. 4. Complex acoustic features depended on innervation of the bird's vocal organ and were lost when the tracheosyringeal nerve was cut. 5. We suggest that stimulation of the forebrain vocal pathway activates a dedicated neural circuit that generates the temporal structure of song and whose specific pattern of activity is programmed during sensorimotor learning in each individual.
Cholinergic modulation of cortical oscillatory dynamics
Authors: Liljenstrom H. , Hasselmo M. E.
Published: December 2017

1. The effect of cholinergic modulation on cortical oscillatory dynamics was studied in a computational model of the piriform (olfactory) cortex. The model included the cholinergic suppression of neuronal adaptation, the cholinergic suppression of intrinsic fiber synaptic transmission, the cholinergic enhancement of interneuron activity, and the cholinergic suppression of inhibitory synaptic transmission. 2. Electroencephalographic (EEG) recordings and field potential recordings from the piriform cortex were modeled with a simplified network in which cortical pyramidal cells were represented by excitatory input/output functions with gain parameters dependent on previous activity. The model incorporated distributed excitatory afferent input and excitatory connections between units. In addition, the model contained two sets of inhibitory units mediating inhibition with different time constants and different reversal potentials. This model can match effectively the patterns of cortical EEG and field potentials, showing oscillatory dynamics in both the gamma (30-80 Hz) and theta (3-10 Hz) frequency range. 3. Cholinergic suppression of neuronal adaptation was modeled by reducing the change in gain associated with previous activity. This caused an increased number of oscillations within the network in response to shock stimulation of the lateral olfactory tract, effectively replicating the effect of carbachol on the field potential response in physiological experiments. 4. Cholinergic suppression of intrinsic excitatory synaptic transmission decreased the prominence of gamma oscillations within the network, allowing theta oscillations to predominate. Coupled with the cholinergic suppression of neuronal adaptation, this caused the network to shift from a nonoscillatory state into an oscillatory state of predominant theta oscillations. This replicates the longer term effect of carbachol in experimental preparations on the EEG potential recorded from the cortex in vivo and from brain-slice preparations of the hippocampus in vitro. Analysis of the model suggests that these oscillations depend upon the time constant of neuronal adaptation rather than the time constant of inhibition or the activity of bursting neurons. 5. Cholinergic modulation may be involved in switching the dynamics of this cortical region between those appropriate for learning and those appropriate for recall. During recall, the spread of activity along intrinsic excitatory connections allows associative memory function, whereas neuronal adaptation prevents the spread of activity between different patterns. During learning, the recall of previously stored patterns is prevented by suppression of intrinsic excitatory connections, whereas the response to the new patterns is enhanced by suppression of neuronal adaptation.
5-HT1B/1D agonist CGS-12066B attenuates clasp knife reflex in the cat
Authors: Miller J. F. , Paul K. D. , Rymer W. Z. , Heckman C. J.
Published: December 2017

1. The effect of intrathecal injection of the selective serotonin (5-HT)1B/1D receptor agonist CGS-12066B maleate (825 nmol) was assessed on stretch-evoked clasp knife inhibition of hindlimb ankle extensor muscle reflex force in precollicular decerebrate cats in which neural transmission in dorsolateral spinal pathways was blocked bilaterally by focal cooling. 2. During cold block, ramp and hold stretches of the medial gastrocnemius muscle (MG) evoked only a brief reflex excitation that was followed by powerful, long-lasting inhibition (the clasp knife reflex). Both the amplitudes of peak force evoked by the ramp and sustained force output during the last 500 ms of the hold phase of the stretch were depressed by > 50%. 3. Reflex force output during the hold portion of stretch was significantly improved on postdrug cold block trials, although peak force remained depressed. CGS-12066B did not significantly alter stretch-evoked force output in decerebrate cats when spinal cord neural transmission was unimpaired. 4. These data suggest that selective 5-HT1B/1D agonists may be of therapeutic usefulness in the treatment of reflex disorders arising from partial spinal cord injury.
Vectorial coding of movement: vision, proprioception, or both?
Authors: Rossetti Y. , Desmurget M. , Prablanc C.
Published: December 2017

1. Subjects were asked to point toward visual targets without visual reafference from the moving hand in two conditions. In both conditions the pointing fingertip was viewed only before movement onset. 2. In one condition, the pointing fingertip was viewed through prisms that created a visual displacement without altering the view of the target. In another experimental condition, vision of the fingertip was not displaced. Comparison of these two conditions showed that virtually shifting finger position before movement through prisms induced a pointing bias in the direction opposite to the shift. The extent of this pointing bias was about one third of the prismatic shift applied to the fingertip. 3. Analysis of movement initial direction demonstrated that it was also less deviated than predicted from the prismatic shift. In addition, the reaction time and movement time of the reaching movement were increased. 4. This result is interpreted in the framework of the vectorial coding of reaching movement. Proprioception and vision provide two possible sources of information about initial hand position, i.e., the origin of the movement vector. The question remains as to how these two sources of information interact in specifying initial hand position when they are simultaneously available. 5. Our results are thus discussed with respect to a visual-to-visual movement vector hypothesis and a proprioceptive-to-visual vector hypothesis. It is argued that the origin of the putative movement vector is encoded by weighted fusion of the visual and the proprioceptive information about hand initial position.
Diverse current and voltage responses to baclofen in an identified molluscan photoreceptor
Authors: Matzel L. D. , Muzzio I. A. , Rogers R. F.
Published: December 2017

1. gamma-Aminobuturic acid-B (GABAB) receptors play a role in the mediation of slow inhibitory postsynaptic potentials in mammalian as well as some nonmammalian species. In identified photoreceptors from the marine mollusc Hermissenda, recent evidence has suggested that GABA, as well as the GABAB receptor agonist baclofen, might simultaneously modulate multiple conductances on the postsynaptic membrane. Here, using intracellular current-clamp and single-electrode voltage-clamp techniques, we have characterized responses to baclofen in the B photoreceptors of the Hermissenda eye. 2. Microapplication of baclofen (12.5–62.5 microM) to the terminal branches of the B photoreceptors induced a slow, concentration-dependent hyperpolarization (approximately 3–8 mV) that was accompanied by a cessation of spontaneous action potentials and a positive shift in firing threshold. Both the hyperpolarization and the shift in spike threshold in response to baclofen were attenuated largely by the K+ channel blocker tetraethylammonium chloride (TEA; 50 mM). 3. Bath application of baclofen (100 microM) decreased the amplitude, duration, and the afterhyperpolarization (AHP) of evoked action potentials. Although baclofen's effect on spike duration and amplitude persisted in the absence of extracellular Ca2+, the reduction of the AHP by baclofen was eliminated, suggesting that multiple conductances mediated the baclofen-induced modification of the action potential. 4. Using a single-electrode voltage-clamp technique, microapplication of baclofen to the terminal branches of the B photoreceptor produced a slow, net outward current (< 0.5 nA) that reversed near the equilibrium potential for K+ and shifted to more positive potentials when extracellular K+ was increased, in approximate agreement with the Nernst equation for K+. 5. Baclofen induced an increase in amplitude of the nonvoltage dependent leak conductance (IL), and the increase was blocked by TEA. The baclofen-induced increase of IL was accompanied by an increase in amplitude and a negative shift in the voltage dependence of a slow, steeply voltage-dependent K+ current (IK), which displays selective sensitivity to TEA but does not normally contribute to leak conductance. The amplitude and steady-state inactivation of a fast, transient K+ current, as well as the amplitude of an inwardly rectifying K+ current were unaffected by baclofen. 6. Both the rate of activation as well as the amplitude of a voltage-dependent Ca2+ current (ICa) were reduced by baclofen. The reduction of ICa resulted in a concomitant suppression of a Ca(2+)-dependent K+ current (IK-Ca) that was sufficient to account for the reduction of the AHP after evoked action potentials.(ABSTRACT TRUNCATED AT 400 WORDS)
Extracellular inhibition and intracellular enhancement of Ca2+ currents by Pb2+ in bovine adrenal chromaffin cells
Authors: Sun L. R. , Suszkiw J. B.
Published: December 2017

1. Effects of highly neurotoxic, inorganic lead ions (Pb2+) on voltage-dependent calcium channels were investigated with the use of the whole cell patch-clamp technique in bovine adrenal chromaffin cells maintained in short-term primary culture (1–5 days). 2. Extracellularly applied Pb2+ induced a concentration-dependent, reversible inhibition of Ca2+ currents, with an estimated IC50 approximately equal to 3.0 x 10(-7) M free Pb2+. 3. Elevation of the intracellular free Ca2+ concentration above 10(-8) M dose-dependently reduced the amplitude of the initial Ca2+ current and increased the exponential rate of current rundown. 4. Intracellularly applied Pb2+ prevented the Ca(2+)-dependent reduction of the initial Ca2+ current amplitude and altered the current rundown kinetics from exponential to linear. The effect was dose dependent and saturable, with an estimated EC50 approximately equal to 2.0 x 10(-10) M free Pb2+. 5. These results indicate that in contrast to extracellular blockade, intracellular Pb2+ promotes Ca2+ currents by attenuating the Ca(2+)-dependent, steady-state inactivation of calcium channels. This provides a novel mechanism through which Pb2+ may disrupt calcium signaling in chronically lead-exposed cells.
Information coding in the rodent prefrontal cortex. I. Single-neuron activity in orbitofrontal cortex compared with that in pyriform cortex
Authors: Schoenbaum G. , Eichenbaum H.
Published: December 2017

1. Extracellular spike activity was recorded from 1,942 single neurons in orbitofrontal cortex (OF) and 591 single neurons in pyriform cortex (PIR) over multiple sessions in rats performing an eight-odor discrimination task in which the stimulus sequence contained predictable associations between particular odor pairs. Neural firing patterns were examined in relation to task events in the current trial and variables associated with current sensory processing, events of recent past trials, and long-term associations involving the odor cues. 2. Overall, 34% of single neurons in OF and 30% of single neurons in PIR fired selectively during one or more salient trial events including trial initiation, odor sampling, performance of the discriminative response, and water consumption. The activity of other cells recorded in OF (13%) and PIR (10%) was suppressed for the duration of each trial. Although the proportion of some cell types differed between the two areas, the firing patterns of OF and PIR neurons were qualitatively indistinguishable. 3. Firing during odor sampling and the discriminative response was influenced by the identity of the current odor. Some cells fired selectively to a single odor, but most cells were coarsely tuned such that they fired to several of the eight odors to differing degrees consistent with previous reports. Considerable odor coding was observed in both OF and PIR. 4. Firing during trial initiation and odor sampling was also influenced by the identity and reward association of the odor presented in the immediately preceding trial. The influence of past odor identity and valence was observed in both OF and PIR. 5. Firing during trial events was also influenced by the acquired associations between odors and their assigned reward contingencies and between pairs of odors involved in predictive relationships. The reward valence of the current odor significantly influenced firing during odor sampling and the discriminative response; some cells responded preferentially to rewarded odors and others to nonrewarded odors. Firing during trial initiation and odor sampling reflected whether or not the odor in the current trial had been predicted by the odor in the preceding trial. In addition, firing during odor sampling reflected the expectation of reward in the following trial that could be inferred from the predictable associations between odors. Each of these properties was observed in both OF and PIR. 6. The findings in OF were consistent with the view that prefrontal subdivisions mediate the temporal organization of complex behaviors within specific informational domains. OF appears to be concerned with the specific domain of olfaction.(ABSTRACT TRUNCATED AT 400 WORDS)
Low-threshold neuronal activity of spinal dorsal horn neurons increases during REM sleep in cats: comparison with effects of anesthesia
Authors: Kishikawa K. , Uchida H. , Yamamori Y. , Collins J. G.
Published: December 2017

1. Cats were prepared for chronic recordings from the lumbar enlargement of the spinal dorsal horn. At the beginning of each recording session, a tungsten microelectrode was advanced through the dura in a physiologically intact, awake, drug-free animal, until amplitude discrimination provided a single neuron with a receptive field on the hindquarters. 2. Extracellular recordings of activity of each neuron were made during receptive field stimulation with tactile and thermal nonnoxious and noxious stimuli. 3. Baseline responses obtained in the awake state were compared with responses of the same neurons during slow-wave or rapid-eye-movement (REM) sleep. In a subpopulation of neurons, the effects of anesthesia (propofol, 7.5 mg/kg iv) were observed after the completion of sleep studies. 4. The low-threshold receptive fields of the seven neurons studied during REM sleep were all increased in size when compared with the baseline value. The average increase was 52.6% (range 26.2–96.7%). 5. The low-threshold receptive fields of the seven neurons studied during REM sleep were reduced by propofol anesthesia by an average of 49.1% (range 29–74%). 6. Neuronal response to receptive field brushing was observed in 15 neurons during REM sleep. The effect of propofol on receptive field brushing was observed in 8 of those neurons. In only one of those eight neurons were the effects of REM sleep and anesthesia in the same direction. 7. Changes in neuronal responses were less consistent during slow-wave sleep but still differed from changes induced by propofol.(ABSTRACT TRUNCATED AT 250 WORDS)
Changes in inhibitory neurotransmission in the CA1 region and dentate gyrus in a chronic model of temporal lobe epilepsy
Authors: Mangan P. S. , Rempe D. A. , Lothman E. W.
Published: December 2017

1. In this report we compare changes in inhibitory neurotransmission within the CA1 region and the dentate gyrus (DG) in a model of chronic temporal lobe epilepsy (TLE). Extracellular and intracellular recordings were obtained in combined hippocampal-parahippocampal slices > or = 1 mo after a period of self-sustaining limbic status epilepticus (SSLSE) induced by continuous hippocampal stimulation. 2. Polysynaptic inhibitory postsynaptic potentials (IPSPs) were induced by positioning electrodes to activate specific afferent pathways and evoking responses in the absence of glutamate receptor antagonists [D(-)-2-amino-5-phosphonovaleric acid (APV) and 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX)]. Polysynaptic IPSPs were evoked in CA1 pyramidal cells from electrodes positioned in stratum radiatum and in stratum lacunosum/moleculare. Polysynaptic IPSPs were evoked in DG granule cells from electrodes positioned over the perforant path located in the subiculum. Monosynaptic IPSPs were induced by positioning electrodes within 200 microns of the intracellular recording electrode (near site stimulation) and stimulating in the presence of APV and CNQX to block ionotropic glutamate receptors. Monosynaptic IPSPs were evoked in CA1 pyramidal cells with electrodes positioned in the stratum lacunosum/moleculare and stratum pyramidale. Monosynaptic IPSPs were evoked in DG granule cells with electrodes positioned in the stratum moleculare. 3. Population spike (PS) amplitudes were employed to assure that a full range of stimulus strengths, from subthreshold for action potentials to an intensity giving maximal-amplitude PSs, was used to elicit polysynaptic IPSPs in CA1 pyramidal cells in both post-SSLSE and control slices. In control tissue, polysynaptic IPSPs were biphasic, composed of early and late events. In post-SSLSE tissue, polysynaptic IPSPs were markedly diminished. The diminution of polysynaptic IPSPs was detected at all levels of stimulus intensity. Both early IPSPs [mediated by gamma-aminobutyric acid-A (GABAA) receptors] and late IPSPs (mediated by GABAB receptors) were diminished. Polysynaptic IPSPs were diminished with both stratum radiatum and with stratum lacunosum/moleculare stimulation. 4. Reversal potentials for either polysynaptic early or polysynaptic late IPSPs evoked in CA1 pyramidal cells by stratum radiatum stimulation were not different in slices from post-SSLSE animals as compared with control animals. Likewise, reversal potentials for either polysynaptic early or polysynaptic late IPSPs evoked by stratum lacunosum/moleculare stimulation did not differ in the two groups. These findings excluded changes in driving force as an explanation for the diminished amplitude of IPSPs in CA1 pyramidal cells in the post-SSLSE model.(ABSTRACT TRUNCATED AT 400 WORDS)
GABA- and glycine-activated currents in the rod bipolar cell of the rabbit retina
Authors: Gillette M. A. , Dacheux R. F.
Published: December 2017

1. Voltage- and ligand-gated currents were recorded from solitary rabbit rod bipolar cells using the whole cell patch-clamp technique. The rod bipolar cell forms a single, stereotypical physiological and morphological class of cells that was easily identified from other neurons and support cells after enzymatic and mechanical dissociation from isolated retina. Protein kinase C immunoreactivity confirmed the validity of using a purely morphological identification of this cell type. 2. Voltage steps in 15-mV increments from a holding potential of -45 mV elicited a large outward current activated near -30 mV. These voltage-gated currents were eliminated by using equimolar substitutions of Cs+ and tetraethylammonium+ for K+ in the pipette, indicating that they represent a mixture of K+ currents. 3. The putative inhibitory neurotransmitters gamma-aminobutyric acid (GABA) and glycine activated inward Cl- currents when pressure-applied from pipettes placed near the axon terminals of rod bipolar cells, which were voltage-clamped at -45 mV. With changes in intracellular or extracellular Cl- concentration, the reversal potential of these ligand-gated currents changed as predicted by the Nernst equation for Cl- activity. The dose-response curves for GABA and glycine were sigmoidal with saturating concentrations of 100 and 300 microM, respectively. 4. GABA-activated currents were 1) reversibly reduced by the allosteric inhibitor picrotoxin and the competitive antagonist bicuculline; 2) potentiated by the benzodiazepine diazepam and the barbiturate barbital sodium; and 3) indistinguishable from muscimol-activated currents. There was no response to the GABAB agonist baclofen. Collectively, these data strongly suggest that the GABA-activated currents in rabbit rod bipolar cells are mediated by the GABAA receptor. This is similar to the GABA-activated currents in other mammalian rod bipolar cells. 5. Application of the conformationally restricted GABA analogue cis-4-aminocrotonic acid (CACA) failed to elicit a response, whereas the conformationally extended GABA analogue trans-4-aminocrotonic acid (TACA) elicited a response similar to that of GABA. Although bicuculline appeared to suppress the GABA-activated current slightly more than the TACA-activated current (not significant using Student's t-distribution), GABA- and TACA-activated currents were equally suppressed by picrotoxin and equally enhanced by diazepam and barbital sodium. These data, coupled with the inefficacy of CACA, argue against the existence of a GABAC-type channel in the rod bipolar cell of the rabbit and suggest that GABA and TACA were activating the same GABAA receptor-channel complex.(ABSTRACT TRUNCATED AT 400 WORDS)
Spreading depression in isolated spinal cord
Authors: Streit D. S. , Ferreira Filho C. R. , Martins-Ferreira H.
Published: December 2017

1. Isolated spinal cord of amphibians is able to express Leao's spreading depression (SD). 2. SD can be evoked when the spinal cord is in an appropriated medium. There are two conditions that favor its elicitation: hypotonicity and low [Cl-] levels in the extracellular microenvironment. 3. Spinal cord SD is accompanied by a stereotyped negative extracellular voltage transient of 17.3 +/- 4.9 (standard deviation) mV amplitude and 1.2 +/- 0.5 min duration concomitantly with a reversible [K+]o increase up to 21.1 +/- 4.6 mM in the extracellular fluid. 4. Potassium salt solution can trigger SD waves that spread at 12 +/- 4.7 mm/min. 5. SD waves occur “spontaneously” in preparations superfused by Ringer solutions with very low [Cl-] (< 20 mM). The frequency of these waves decreases, and they may stop if [Mg2+] is increased.
Synaptic current kinetics in a solely AMPA-receptor-operated glutamatergic synapse formed by rat retinal ganglion neurons
Authors: Taschenberger H. , Engert F. , Grantyn R.
Published: December 2017

1. Postnatal rat retinal ganglion cells (RGCs) can be maintained and identified in dissociated long-term culture. After 4-7 days in vitro they form glutamatergic synapses with other RGCs or putative amacrine cells. Here we intended to characterize the postsynaptic features of these in vitro synapses. 2. Pair patch-clamp recordings in the whole cell configuration were performed to study the properties of synaptic glutamate receptors. Immunohistochemically and physiologically identified RGCs were activated by short depolarizing voltage steps. This elicited glutamatergic excitatory postsynaptic currents (EPSCs) in coupled neurons. At room temperature, evoked EPSCs (eEPSCs) had latencies between 3 and 7 ms and amplitudes between 36.4 and 792.6 pA. 3. Postsynaptic neurons were electrotonically compact and therefore well suited for analysis of fast synaptic events. All cells were responsive to exogenous glutamate, alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and N-methyl-D-aspartate (NMDA). The current-voltage relationships of AMPA-activated currents were linear, whereas NMDA-induced whole cell currents displayed the typical characteristics including a negative slope conductance in the presence of Mg2+. In contrast to AMPA-activated currents, NMDA-activated currents had the usual slow onset and decay. 4. RGCs obviously failed to generate NMDA-receptor-mediated EPSCs, because all postsynaptic cells lacked a slow current component even in the absence of added Mg2+ and in the presence of glycine. Retinal eEPSCs were completely blocked by 6,7-dinitroquinoxaline-2,3-dione (DNQX). 5. eEPSCs as well as spontaneous EPSCs (sEPSCs) were characterized by a very rapid time course. In eEPSCs, 20-80% rise times and time constants of decay (tau DS) were on average 0.64 and 1.96 ms, respectively. eEPSCs were extremely fast, with average rise times of 0.34 ms and tau DS of 1.20 ms. The latter numbers closely correspond to the values obtained for DNQX-sensitive miniature EPSC (mEPSC) in postnatal day 5 rat RGCs in situ. 6. To clarify whether the decay of fast AMPA-receptor-mediated EPSCs of retinal neurons was determined by the onset of glutamate receptor desensitization, we compared the decay of sEPSCs with the decay of the glutamate response of excised out-side-out membrane patches. Glutamate-activated currents were elicited by a rapid superfusion device (time constant of rise = 0.7 ms). The response to 1 mM of glutamate decayed 2 to 4 times more slowly than the sEPSCs. 7. These results suggest that desensitization did not limit the rate of decay of purely AMPA-mediated EPSCs in response to ganglion cell activation.(ABSTRACT TRUNCATED AT 400 WORDS)
Accumulation of inactivation in a cloned transient K+ channel (AKv1.1a) of Aplysia
Authors: Furukawa Y.
Published: December 2017

1. Inactivation of a cloned Aplysia K+ channel, AKv1.1a, expressed in Xenopus oocytes was examined by a cell-attached macropatch recording. A fast macroscopic inactivation (the time constant for decay was in the range of 20-40 ms) in response to a depolarizing command pulse was insensitive to the concentration of external K+ (2-100 mM KCl). 2. By contrast, recovery from inactivation was extremely slow and dependent on external K+. When the concentration of external KCl was 2-3 mM, a patched membrane had to be held at hyperpolarized potential for > 40 s for a full recovery. The recovery was greatly accelerated if external K+ concentration was increased. A tail current following a command pulse long enough to inactivate most of the channels showed a marked rising phase. 3. A consequence of the slow recovery from inactivation was that AKv1.1a showed a marked accumulation of the inactivation following repetitive pulses, even at low frequency (< 0.1 Hz). When two depolarizing pulses were applied at a short interval, the current during a second pulse was smaller than the current at the end of the preceding pulse. This is a phenomenon called "cumulative inactivation." The onset and the extent of cumulative inactivation of AKv1.1a were voltage dependent but relatively insensitive to external K+ concentration. An amino terminal deletion mutant of AKv1.1a that lacks the fast N-type inactivation did not show cumulative inactivation. 4. These results suggest that the inactivation gating by the amino terminal region of AKv1.1a has a similarity to open-channel blockade, and that the cumulative inactivation can also be dependent on the amino terminal cytoplasmic domain of K+ channels.
Effect of MLF transection on the vertical vestibulocollic reflex in decerebrate cats
Authors: Thomson D. B. , Ikegami H. , Wilson V. J.
Published: December 2017

1. In the cat, motoneurons supplying biventer cervicis, complexus and rectus capitis posterior receive disynaptic input from the posterior semicircular canals and from the contralateral anterior canal via the medial vestibulospinal tract (MVST). Disynaptic excitation from the ipsilateral anterior canal reaches these motoneurons via the lateral vestibulospinal tract. 2. We hypothesized that if the MVST has a unique role in the production of the vertical vestibulocollic reflex (VCR) in these muscles then interruption of this tract by transection of the medial longitudinal fasciculus (MLF) would change the VCR responses. Specifically, response vector orientations would shift toward the plane of the ipsilateral anterior canal, and response gains would drop at high frequencies. 3. We lesioned the MLF bilaterally and observed no substantial effect on neck-muscle responses. Response vector orientations did not shift systematically toward a single plane, nor was there a consistent decrease in response gains at high frequencies. 4. As in the horizontal VCR, there is no unique contribution from MVST neurons; parallel pathways must play an important role in the vertical VCR.
Computation of long-distance propagation of impulses elicited by Poisson-process stimulation
Authors: Moradmand K. , Goldfinger M. D.
Published: December 2017

1. The purpose of this work was to determine whether computed temporally coded axonal information generated by Poisson process stimulation were modified during long-distance propagation, as originally suggested by S. A. George. Propagated impulses were computed with the use of the Hodgkin-Huxley equations and cable theory to simulate excitation and current spread in 100-microns-diam unmyelinated axons, whose total length was 8.1 cm (25 lambda) or 101.4 cm (312.5 lambda). Differential equations were solved numerically, with the use of trapezoidal integration over small, constant electrotonic and temporal steps (0.125 lambda and 1.0 microsecond, respectively). 2. Using dual-pulse stimulation, we confirmed that for interstimulus intervals between 5 and 11 ms, the conduction velocity of the second of a short-interval pair of impulses was slower than that of the first impulse. Further, with sufficiently long propagation distance, the second impulse's conduction velocity increased steadily and eventually approached that of the first impulse. This effect caused a spatially varying interspike interval: as propagation proceeded, the interspike interval increased and eventually approached stabilization. 3. With Poisson stimulation, the peak amplitude of propagating action potentials varied with interspike interval durations between 5 and 11 ms. Such amplitude attenuation was caused by the incomplete relaxation of parameters n (macroscopic K-conductance activation) and h (macroscopic Na-conductance inactivation) during the interspike period. 4. The stochastic properties of the impulse train became less Poisson-like with propagation distance. In cases of propagation over 99.4 cm, the impulse trains developed marked periodicities in Interevent Interval Distribution and Expectation Density function because of the axially modulated transformation of interspike intervals. 5. Despite these changes in impulse train parameters, the arithmetic value of the mean interspike interval did not change as a function of propagation distance. This work showed that in theory, whereas the pattern of Poisson-like impulse codes was modified during long-distance propagation, their mean rate was conserved.
Transfer characteristics of X LGN neurons in cats reared with early discordant binocular vision
Authors: Cheng H. , Chino Y. M. , Smith E. L. , Hamamoto J. , Yoshida K.
Published: December 2017

1. The effects of early discordant binocular vision on the functional development of the cat lateral geniculate nucleus (LGN) were investigated by quantitatively comparing responses of individual LGN neurons with their direct retinal inputs. 2. Unilateral convergent strabismus (esotropia) was surgically induced in 11 kittens at the age of 3 wk. After the animals had reached 9 mo of age, extracellular microelectrode recordings were made from individual X LGN units in lamina A and A1 of anesthetized and paralyzed cats. Responses were measured for drifting sinusoidal gratings. Within-unit comparisons of LGN action potentials (LGN output) and S potentials (retinal input) were performed to determine the nature of signal transfer in the units driven by the deviating (N = 42) or nondeviating eyes (N = 29) of strabismic cats. The results were compared with similar data (N = 29) obtained from nine normal control cats. 3. The spatial resolution of many individual LGN units in strabismic cats was abnormally reduced relative to their retinal inputs. These differences were more pronounced in units that received inputs from the nasal retina of the contralateral eye. The resolution loss was closely associated with a dramatic decrease in the strength of the receptive field center mechanism of LGN units relative to their retinal inputs. Moreover, the efficiency of signal transfer for high-spatial-frequency stimuli, determined by the transfer ratio (response amplitude of LGN action potentials/amplitude of S potentials), was significantly lower in strabismic cats compared with normal controls. 4. In strabismic cats, contrast thresholds for the action potentials of individual LGN units were significantly higher than those determined for the S potentials. In normal cats, the input-output differences in contrast threshold were negligible. The observed contrast sensitivity loss was more pronounced for high-spatial-frequency stimuli. 5. The speed of signal transfer was significantly decreased in the LGNs of strabismic animals. The visual response latencies of many, but not all, X LGN cells in the strabismic cats were abnormally long when compared with those in normal control units, whereas SP latencies were virtually the same for strabismic and normal cats. Abnormal latencies were prevalent in units that exhibited contrast threshold deficits, and were more severe among the units receiving input from the contralateral nasal retina. 6. The deficits in strabismic cats were found in the LGN units innervated by the deviating and nondeviating eyes. However, for the majority of response measures, the units innervated by the deviating eyes showed notably larger deficits. 7. We conclude that the fidelity of signal transfer from the retina to the LGN is significantly reduced in cats reared with discordant binocular visual experience. Thus the adverse effects of early strabismus are not confined, at least in cats, to the visual cortex.
Calcium-activated release of nitric oxide potentiates excitatory synaptic potentials in immature rat sympathetic preganglionic neurons
Authors: Wu S. Y. , Dun N. J.
Published: December 2017

1. Whole cell patch recordings were made from sympathetic preganglionic neurons (SPNs), the majority of which contain brain nitric oxide synthase (bNOS), in transverse spinal cord slices of 12- to 16-day-old rats. 2. Repetitive discharge of SPNs induced by a train of depolarizing current pulses (40 Hz. 10 s) was followed by a long-lasting increase (140 +/- 22%, mean +/- SD) of the amplitude of excitatory postsynaptic potentials (EPSPs) evoked by stimulation of lateral funiculus in 50 of 75 SPNs. 3. In slices pretreated with the nitric oxide synthase inhibitors, NG-monomethyl-L-arginine (L-NMA: 100 microM) or Nw-nitro-L-arginine (L-NARG; 30 microM) or with bovine hemoglobin (100 microM), repetitive discharge of SPNs was not followed by a significant increase of EPSPs. 4. Superfusing the slices with L-arginine (L-Arg, 300 microM) but not D-Arg reversibly increased the EPSPs by an average of 140 +/- 19%. 5. Inclusion of the Ca2+ chelator 1.2-bis(2-aminophenoxy)- ethane-N,N,N',N'-tetraacetic acid (BAPTA, 1 mM) in the patch electrodes resulted in no significant increase of EPSPs after repetitive discharge in all cells studied. 6. It is concluded that during repetitive discharge of SPNs, Ca2+ influx via voltage-gated channels activates bNOS, resulting in a release of nitric oxide and potentiation of EPSPs.
Acute activation and inactivation of macaque frontal eye field with GABA-related drugs
Authors: Dias E. C. , Kiesau M. , Segraves M. A.
Published: December 2017

1. This project tests the behavioral effects of reversible activation and inactivation of sites within the frontal eye field of rhesus monkeys with microinjections of the gamma-aminobutyric acid (GABA)-related drugs bicuculline and muscimol. 2. Muscimol injections impaired the monkeys' ability to make both visually and memory-guided saccades to targets at the center of the area represented by the injection site. The latencies of saccades to targets in regions flanking the injection were increased. For memory-guided saccades, saccades in the direction opposite to that represented by the injection site, were made with shorter latency than controls and often occurred before the movement cue. 3. Bicuculline injections produced irrepressible saccades equivalent to the saccade vector represented by the injection site, often in a staircase of several closely spaced movements. 4. Both substances decreased the accuracy of fixation of a central light. The distribution of points of fixation on different trials was diffuse, and the angle of gaze tended to deviate towards the side of the injection. 5. The results of these acute injections are similiar to those observed in the superior colliculus and are much more substantial than the effects observed in the long term after surgical removal of the frontal eye field. The results of this study promote a central role for the frontal eye field in the generation of all voluntary saccades and in the control of fixation.
Contrasting locations of pallidal-receiving neurons and microexcitable zones in primate thalamus
Authors: Buford J. A. , Inase M. , Anderson M. E.
Published: December 2017

1. In two awake, juvenile male Macaca fascicularis monkeys, microstimulation was applied in ventralis anterior (VA), ventralis lateralis (VL), or ventralis posterior lateralis (VPL) of the thalamus. Thalamic recording was used to identify the region that contained pallidal-receiving (PR) thalamic neurons, cells that responded orthodromically to stimulation in the internal pallidal segment (GPi). Thalamic stimulation was used to elicit motor responses. Penetrations in the thalamus and the pallidum focused on areas with activity related to contralateral arm movement. Fifty-one PR cells were identified electrophysiologically in VL oralis (VLo), VL caudalis (VLc) and VA pars parvocellularis (VApc). 2. With a subject at rest, trains of stimuli were applied through the thalamic microelectrode. Palpable or visible muscle twitches or joint movements were evoked by short trains (12 pulses) of stimuli applied in VLc and VPL oralis (VPLo); thresholds there ranged from 5 to 75 microA. In VA and VLo, areas where PR neurons were located, even longer trains (24 pulses) of stimuli with currents up to 200 microA usually failed to evoke movement. In the caudal portions of VLo, near VPLo, there were some microexcitable sites found near PR cells where stimuli at approximately 50 microA elicited movement. 3. From microstimulation studies combined with histological reconstruction, Ashe and co-workers hypothesized that microexcitable zones were cerebellar receiving areas (CR) and nonexcitable zones were PR areas. Our data support theirs and add electrophysiological identification of PR areas. Further, we injected wheat germ agglutinin-horseradish peroxidase (WGA-HRP) into the thalamus at one of the more rostral microexcitable sites, just caudal and lateral to identified PR cells. The tetra-methyl benzidine-reacted HRP label was found in the contralateral deep cerebellar nuclei (DCN) but not in ipsilateral GPi, showing that even this rostral microexcitable zone was a CR area. 4. Together with evidence from the literature, the data are consistent with the hypothesis that PR cells have relatively weak access to spinal-destined motor outputs, whereas thalamocortical neurons from VPLo and VLc have more secure access. In addition to characteristics of cell discharge and responses to somatosensory stimulation, microexcitability may be a further aid in tentative electro-physiological identification of PR versus CR areas of the motor thalamus without necessarily recording thalamic neuronal responses to stimulation in GPi or the DCN.
Activity patterns of the B31/B32 pattern initiators innervating the I2 muscle of the buccal mass during normal feeding movements in Aplysia californica
Authors: Hurwitz I. , Neustadter D. , Morton D. W. , Chiel H. J. , Susswein A. J.
Published: December 2017

1. B31 and B32 are pattern-initiator neurons in the buccal ganglia of Aplysia. Along with the B61/B62 neurons, B31/B32 are also motor neurons that innervate the 12 buccal muscle via the I2 nerve. This research was aimed at determining the physiological functions of the B31/B32 and B61/B62 neurons, and of the I2 muscle. 2. Stimulating the I2 muscle in the radula rest position produces radula protraction. In addition, in behaving animals lesioning either the muscle or the I2 nerve greatly reduces radula protraction. 3. During buccal motor programs in reduced preparations, B31/B32 and B61/62 fire preceding activity in neuron B4, whose firing indicates the onset of radula retraction. In addition, during both ingestion-like and rejection-like patterns the activity in the I2 nerve is correlated with protraction. 4. B31/B32 fire at frequencies of 15-25 Hz. Neither B31/B32 nor B61/B62 elicit facilitating end-junction potentials (EJPs) and electromyograms (EMGs) in the I2 muscle. EMGs from B31/B32 are smaller than those from B61/B62. B31/B32 and B61/B62 innervate all areas of the muscle approximately uniformly. 5. In behaving animals, EMGs consistent with B31/B32 activity are seen in the I2 muscle during the protraction phase of biting, swallowing, and rejection movements. In addition, the I2 muscle receives inputs that cannot be attributed to either the B31/B32 or B61/B62 neurons, either because the potentials are too large, firing frequencies are too low, or a prominent facilitation is seen. Such potentials are associated with lip movements, and also with radula retraction. 6. EMGs were recorded from the I2 muscle during feeding behavior after a lesion of the I2 nerve. Animals that had severe deficits in protraction showed no activity consistent with B31/B32 or B61/B62, but did show activity during retraction. 7. Our data indicate that the I2 muscle and the B31/B32 motor neurons are essential constituents contributing to protraction movements. Activity in these neurons is associated with radula protraction, which occurs as a component of a number of different feeding movements. The I2 muscle may also contribute to retraction, via activation by other motor neurons.
AMPA receptor heterogeneity in rat hippocampal neurons revealed by differential sensitivity to cyclothiazide
Authors: Fleck M. W. , Bahring R. , Patneau D. K. , Mayer M. L.
Published: December 2017

1. The kinetics of onset of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor desensitization by glutamate, and the extent of attenuation of AMPA receptor desensitization by cyclothiazide, showed pronounced cell-to-cell variation in cultures of rat hippocampal neurons. Cultures prepared from area CA1 stratum radiatum tended to show weaker modulation by cyclothiazide than cultures prepared from the whole hippocampus. 2. Kinetic analysis of concentration jump responses to glutamate revealed multiple populations of receptors with fast (approximately 400 ms), intermediate (approximately 2-4 s), and slow (> 20 s) time constants for recovery from modulation by cyclothiazide. The amplitudes of these components varied widely between cells, suggesting the existence of at least three populations of AMPA receptor subtypes, the relative density of which varied from cell to cell. 3. The complex patterns of sensitivity to cyclothiazide seen in hippocampal neurons could be reconstituted by assembly of recombinant AMPA receptor subunits generated from cDNAs encoding the flip (i) and flop (o) splice variants of the GluR-A and GluR-B subunits. Recovery from modulation by cyclothiazide was slower for GluR-AiBi and GluR-AoBi than for GluR-AiBo and GluR-AoBo. 4. Coexpression of the flip and flop splice variants of GluR-A, in the absence of GluR-B, revealed that heteromeric AMPA receptors with intermediate sensitivity to cyclothiazide, similar to responses observed for the combinations GluR-AoBi or GluR-AiBo, could be generated independently of the presence of the GluR-B subunit. However, recovery from modulation by cyclothiazide was twofold slower for GluR-AiBi than for homomeric GluR-Ai, indicating that the GluR-A and GluR-B subunits are not functionally equivalent in controlling sensitivity to cyclothiazide. 5. These results demonstrate that AMPA receptors expressed in hippocampal neurons are assembled in a variety of subunit and splice variant combinations that might serve as a mechanism to fine-tune the kinetics of synaptic transmission.