bluuebunny/crossref_metadata_2025 huggingface dataset:
Adenosine modulates voltage-gated Ca2+ channels in adult rat sympathetic neurons
Authors: Zhu Y. , Ikeda S. R.
Published: December 2017

1. Ca(2+)-channel modulation by adenosine was investigated in enzymatically dispersed adult rat superior cervical ganglion (SCG) neurons using the whole-cell variant of the patch-clamp technique. 2. Adenosine produced a concentration-dependent decrease in the Ca(2+)-current amplitude with an EC50 of 174 nM and maximum inhibition of 36%. The effects of adenosine on the Ca2+ current were both time and voltage dependent. The inhibition was maximal at +10 mV and decreased at either hyperpolarizing or depolarizing potentials. 3. The inhibitory response desensitized after prolonged (> 1 min) exposure to 10 microM adenosine, whereas multiple brief (< 30 s) applications slightly decreased the subsequent response. 4. Adenosine-induced Ca2+ current inhibition was mediated by an A1-type adenosine receptor, because the half-maximal inhibition value for an A1 receptor selective agonist, chloro-N-cyclopentyladenosine, was 1,000-fold lower than that for an A2 receptor selective agonist, 2-p-(2-carboxyethyl)phenethylamino-5'-N-ethylcarbozamido adenosine hydrochloride (33 nM vs. 40 microM, respectively). 5. A guanine nucleotide binding protein (G protein) appeared to be involved in the action of adenosine, because: 1) the adenosine-induced current inhibition could be largely relieved by depolarizing voltage prepulses; 2) tail current analysis revealed that adenosine shifted Ca(2+)-channel activation to more depolarized potentials; and 3) adenosine inhibition was abolished by 2 mM intracellular guanosine 5'-O-(2-thiodiphosphate) or 500 ng/ml pertussis toxin pretreatment. 6. Adenosine did not appear to inhibit L-type Ca2+ channels, because the prolonged tail current component induced by the dihydropyridine "agonist" 2,6-dimethy-3-carbomethoxy-5-nitro-4-(2-trifluoromethyl-phenyl)- 1,4-dihydropyridine (2 microM) was not affected by adenosine. 7. Adenosine-induced inhibition was reduced to approximately 15% after application of 10 microM omega-conotoxin GVIA, suggesting that adenosine primarily inhibits N-type Ca2+ channels. The Ca(2+)-current component resistant to omega-conotoxin GVIA was also resistant to omega-agatoxin IVA (200 nM), suggesting a lack of P-type of Ca2+ channels in SCG neurons. 8. In conclusion, adenosine produces a dose-, time-, and voltage-dependent inhibition of Ca2+ currents in SCG neurons. Adenosine acts on an A1 adenosine receptor subtype in SCG neurons via a pertussis toxin-sensitive G protein to inhibit N-type Ca2+ channels and an unidentified Ca(2+)-current component. Modulation of Ca2+ currents by adenosine may be an important mechanism for its inhibitory effect on neurotransmitter release in sympathetic neurons.
Regular oscillations of synaptic activity in spinal networks in vitro
Authors: Streit J.
Published: December 2017

1. Spontaneous synaptic potentials were recorded in motoneurons grown in organotypic slice cultures of embryonic rat spinal cord. In 71 of 85 cells these potentials appeared without obvious temporal structure (random patterns); in the remaining 14 cells they appeared in bursts (rhythmic patterns). 2. Random activity patterns could be converted into rhythmic patterns by treating the cultures with strychnine, bicuculline, or both. The excitatory amino acid N-methyl-D-aspartate (NMDA) transiently increased the rate of spontaneous synaptic activity without inducing rhythmic patterns. The NMDA antagonist 7-chloro-kynurenate reduced the burst rate while leaving the burst length unchanged in rhythmic patterns. In random patterns it reduced the rate of spontaneous synaptic activity by 68%. 3. Histograms of interevent times of the random patterns were best fitted by the sum of two expontentials, suggesting that the random type of activity could not be described simply as a Poisson process but involved at least one additional mechanism. 4. Rhythmic patterns consisted of bursts of activity with a mean burst length of 2.2 s that were separated by interburst intervals with a mean length of 6.6 s. Within the bursts autocorrelograms revealed regular oscillations with a mean period of 226 ms in 6 of 11 experiments with rhythmic patterns. The period showed little variation between individual experiments (202-288 ms). In random patterns no oscillations were detected. 5. Within the spontaneous bursts the excitatory postsynaptic potentials (EPSPs) progressively declined in amplitude. A corresponding depression of EPSPs was observed when trains of electrical stimuli were applied at 5 Hz to the dorsal horns of the spinal cord slices.(ABSTRACT TRUNCATED AT 250 WORDS)
Opioid-glutamate interactions in rat locus coeruleus neurons
Authors: Oleskevich S. , Clements J. D. , Williams J. T.
Published: December 2017

1. The effect of mu-opioids on the glutamate response was investigated in rat locus coeruleus (LC) neurons by intracellular recording in the brain slice preparation. Glutamate responses were evoked by bath application of selective glutamate agonists, glutamate iontophoresis, and stimulation of excitatory afferents. 2. The mu-opioid agonist D-Ala2-MePhe4-Gly-ol5-enkephalin (DAMGO; 1 microM) potentiated the response to bath application of N-methyl-D-aspartate (NMDA) and alpha-amino-3-hydroxy-5-methyl-4-isoxazole proprionic acid by 91 and 142%, respectively, in slices cut in the horizontal plane. The mechanism of action of this effect was investigated under conditions that limited the DAMGO-induced hyperpolarization and improved the space clamp of the neuron through 1) addition of barium, 2) increase in extracellular potassium concentration, 3) sectioning of the LC in the coronal plane, and 4) addition of carbenoxolone. Each experimental manipulation decreased the DAMGO outward current and reduced the mu-opioid potentiation of the glutamate response. The results suggest that the mu-opioid-mediated potentiation of the glutamate response is dependent on membrane hyperpolarization. 3. Neither forskolin nor the phorbol ester 4b-phorbol 12,13-dibutyrate (PDBu) altered the glutamate-mediated inward currents. The potentiation of the glutamate response by DAMGO was not affected by PDBu. 4. The mu-opioids DAMGO and [met]5enkephalin (10 microM) did not significantly affect the NMDA receptor-mediated depolarization (mean 14%) evoked by local application of glutamate but inhibited the NMDA receptor-mediated synaptic potential (mean 25%).(ABSTRACT TRUNCATED AT 400 WORDS)
Responses of caudal medullary raphe neurons to natural vestibular stimulation
Authors: Yates B. J. , Goto T. , Kerman I. , Bolton P. S.
Published: December 2017

1. Over two thirds of caudal medullary raphespinal neurons respond to electrical stimulation of the vestibular nerve, and it has been suggested that these neurons may participate in the generation of vestibulospinal and vestibulosympathetic reflexes. The objective of the present study was to determine which vestibular endorgans (semicircular canals or otolith organs) provide inputs to these cells. 2. Experiments were conducted on decerebrate cats that were baroreceptor denervated and vagotomized, and that had a cervical spinal cord transection so that inputs from tilt-sensitive receptors outside of the labyrinth did not influence the units we recorded. 3. In most experiments, vertical vestibular stimulation was used to stimulate the anterior and posterior semicircular canals and the otolith organs. The plane of whole body rotation that produced maximal modulation of a neuron's firing rate (response vector orientation) was measured at one or more frequencies between 0.1 and 0.5 Hz. Neuron dynamics were then studied with sinusoidal (0.02-1 Hz) stimuli aligned with this orientation. Alternatively, in two animals horizontal rotations at 0.5 and 1.0 Hz were employed to stimulate the horizontal semicircular canals. 4. The properties of raphespinal neurons were similar to those of a larger sample of raphe neurons studied that either could not be antidromically activated from the cervical spinal cord or were not tested for a spinal projection. In response to vertical vestibular stimulation, > 85% of caudal medullary raphe neurons had response gains that remained relatively constant across stimulus frequencies, like regularly firing otolith afferents.(ABSTRACT TRUNCATED AT 250 WORDS)
Voltage-dependent block by neomycin of the ATP-induced whole cell current of guinea-pig outer hair cells
Authors: Lin X. , Hume R. I. , Nuttall A. L.
Published: December 2017

1. The effects of externally applied ATP and neomycin on whole cell currents of isolated guinea pig cochlear outer hair cells (OHCs) were studied using the whole cell voltage-clamp technique. In OCHs held at -70 mV, ATP activated a large inward current. In the presence of neomycin, the ATP-induced whole cell current activated along a relatively unaltered time course, but the current then decreased to a reduced steady level. The neomycin inhibition of the ATP-induced current was dose dependent. The half-inhibitory concentration (IC50) of neomycin measured at steady state was estimated to be 90 microM. 2. Neomycin inhibition of the ATP response could not be reversed by increasing the concentration of ATP, indicating that the effect was noncompetitive. The inhibition was voltage dependent and was greatly reduced when OHCs were held at positive potentials. 3. Cells treated with 100 microM ATP gave maximal current responses. Addition of neomycin substantially increased membrane current noise of the 100 microM ATP responses. When neomycin concentration was varied from 10 to 500 microM, the current noise level peaked between 50 and 100 microM. The noise increase was observed at negative holding potentials but not at positive potentials. 4. The neomycin-induced whole cell current noise was used to estimate the size of the underlying elementary current. The ATP-induced single channel current of OHCs at -70 mV was estimated to be approximately 0.3 pA. The number of ATP-activated channels in a single OHC was estimated to be in the range of a few thousand. 5. The characteristics of the neomycin inhibition of ATP-induced currents were consistent with an open channel blocking mechanism. Analysis of the voltage dependence of the steady state neomycin inhibition suggested a neomycin binding site at an electrical distance of 0.3 from the extracellular side.
Dietary Na(+)-restriction prevents development of functional Na+ channels in taste cell apical membranes: proof by in vivo membrane voltage perturbation
Authors: Ye Q. , Stewart R. E. , Heck G. L. , Hill D. L. , DeSimone J. A.
Published: December 2017

1. Chorda tympani (CT) neural responses to NaCl were recorded while the potential across the apical membrane of taste cells was perturbed by voltage clamp in rats fed a Na(+)-restricted diet pre- and postnatally (Na(+)-restricted rats) and in controls. 2. Control rats gave CT responses that were enhanced at negative voltage clamp and suppressed at positive voltage clamp. In contrast, CT responses from Na(+)-restricted rats were virtually voltage insensitive. 3. Analysis of the voltage-sensitivity of the CT response shows that Na(+)-restricted rats have < 10% of the density of functional apical Na+ channels normally present in control rats demonstrating that early dietary Na(+)-restriction prevents the functional expression of these key elements in salt taste transduction. Furthermore, the data demonstrate the value of this technique in assessing involvement of distinct cellular domains in taste transduction.
Neuronal activity in the caudolateral peribrachial pons: relationship to PGO waves and rapid eye movements
Authors: Datta S. , Hobson J. A.
Published: December 2017

1. The present study was performed to examine the hypothesis that the caudolateral peribrachial area (C-PBL) may be directly involved in shifting the brain from the nonpontogeniculooccipital (non-PGO)-related states of waking (W) and slow-wave sleep (S) to the PGO-related states of slow-wave sleep with PGO waves (SP) and rapid eye movement (REM) sleep. 2. To test this hypothesis at the cellular level, we have recorded a sample of 226 spontaneously discharging units of the C-PBL during natural sleep-waking cycles in unanesthetized head-restrained cats and have correlated the action-potential data with the PGO waves. 3. Of these 226 cells, 67.26% (n = 152) were called PGO state-on units because they increased or began firing 15'5 s before the first PGO wave of SP and maintained their high firing rate throughout SP (31.30 +/- 6.0 Hz, mean +/- SD) and REM sleep (39.46 +/- 6.70 Hz); their firing rates in W (0.45 +/- 0.85) and S (0.70 +/- 1.26) were much lower. Among these PGO state-on neurons, 28.94% (n = 44) discharged high-frequency (> 500 Hz) spike bursts on the background of tonically increased firing rates during the PGO-related states. Contrastingly, 14.16% (n = 32) of the cells (called PGO state-off units) fired tonically during W (11.54 +/- 4.15) and S (9.43 +/- 3.87) but stopped or decreased firing 25–15 s before the first PGO wave of SP; their activity remained suppressed throughout SP (0.19 +/- 0.44) and REM sleep (0.03 +/- 0.17). The remaining 18.58% (n = 42) cells fired (9–10 Hz) tonically but were unrelated to the wake-sleeping cycle. 4. During SP and REM sleep, primary PGO waves were found to appear with equal frequency in each lateral geniculate body (LGB). During REM sleep these primary waves were ipsilateral to the direction of phasic rapid eye movements as previously reported by Nelson et al. (1983). 5. During SP and REM sleep PGO state-on burst cells fired high-frequency bursts on a background of tonic activity in association with each ipsilateral primary LGB PGO wave. The first spike of a burst preceded the beginning of the negative component of the ipsilateral LGB PGO waves by 25 +/- 7.5 ms. On the basis of their sustained firing and the latency of their PGO-related bursting, we call these neurons long-lead PGO-on burst-tonic cells.(ABSTRACT TRUNCATED AT 400 WORDS)
Corticocortical and thalamocortical responses of neurons in the monkey primary motor cortex and their relation to a trained motor task
Authors: Aizawa H. , Tanji J.
Published: December 2017

1. We studied the responsiveness of neurons in the primary motor cortex (MI) of monkeys (Macacafuscata) to electrical stimulation of the supplementary motor area (SMA), primary sensory cortex (SI), and the ventral subnucleus of the thalamus (VPLo) with chronically implanted electrodes. 2. All neurons examined in this study were characterized by their relation to a motor task performed by the animals. They responded to stimulation of the cortical or thalamic area with excitation from one area alone (n = 128) or from multiple areas (n = 84) of all combinations. In a majority of neurons, response latencies to both cortical and thalamic stimulation were within 5 ms. 3. A vast majority of neurons (80%) that were active during a preparatory period for forthcoming reaching movements were activated by SMA stimulation. They were activated only infrequently by SI or thalamic stimulation. 4. Movement-related neurons (active immediately before and during reaching movements) were activated by thalamic, SI, or SMA stimulation or by any combination of those stimuli. More than half of the movement-related neurons activated exclusively by either thalamic or SMA stimulation exhibited activity onset times earlier than those observed in the earliest muscles. By contrast, most movement-related neurons that responded only to SI stimulation were late in their activity onset. 5. These findings suggest that the SMA input to MI is important in developing a preparatory type of activity in MI, whereas the thalamus (VPLo) provides substantial inputs in movement execution. The roles played by inputs from SI and SMA in relation to motor execution are debatable and are discussed here with reference to previous reports.
Modeling three-dimensional velocity-to-position transformation in oculomotor control
Authors: Schnabolk C. , Raphan T.
Published: December 2017

1. A considerable amount of attention has been devoted to understanding the velocity-position transformation that takes place in the control of eye movements in three dimensions. Much of the work has focused on the idea that rotations in three dimensions do not commute and that a "multiplicative quaternion model" of velocity-position integration is necessary to explain eye movements in three dimensions. Our study has indicated that this approach is not consistent with the physiology of the types of signals necessary to rotate the eyes. 2. We developed a three-dimensional dynamical system model for movement of the eye within its surrounding orbital tissue. The main point of the model is that the eye muscles generate torque to rotate the eye. When the eye reaches an orientation such that the restoring torque of the orbital tissue counterbalances the torque applied by the muscles, a unique equilibrium point is reached. The trajectory of the eye to reach equilibrium may follow any path, depending on the starting eye orientation and eye velocity. However, according to Euler's theorem, the equilibrium reached is equivalent to a rotation about a fixed axis through some angle from a primary orientation. This represents the shortest path that the eye could take from the primary orientation in reaching equilibrium. Consequently, it is also the shortest path for returning the eye to the primary orientation. Thus the restoring torque developed by the tissue surrounding the eye was approximated as proportional to the product of this angle and a unit vector along this axis. The relationship between orientation and restoring torque gives a unique torque-orientation relationship. 3. Once the appropriate torque-orientation relationship for eye rotation is established the velocity-position integrator can be modeled as a dynamical system that is a direct extension of the one-dimensional velocity-position integrator. The linear combination of the integrator state and a direct pathway signal is converted to a torque signal that activates the muscles to rotate the eyes. Therefore the output of the integrator is related to a torque signal that positions the eyes. It is not an eye orientation signal. The applied torque signal drives the eye to an equilibrium orientation such that the restoring torque equals the applied torque but in the opposite direction. The eye orientation reached at equilibrium is determined by the unique torque-orientation relation. Because torque signals are vectors, they commute.(ABSTRACT TRUNCATED AT 400 WORDS)
Defense reaction in the pond snail Planorbis corneus. II. Central pattern generator
Authors: Arshavsky Y. I. , Deliagina T. G. , Okshtein I. L. , Orlovsky G. N. , Panchin Y. V. , Popova L. B.
Published: December 2017

1. In the isolated CNS of the pond snail Planorbis corneus, spontaneous bursts of activity in the motor neurons (MNs) supplying the columellar muscle were occasionally observed. The biphasic pattern of this activity, with a shorter (3-5 s) initial burst and longer (20-40 s) subsequent burst, was similar to that of the motor output during the general ("whole-body") defense reaction. In preparations consisting of the CNS isolated with the columellar muscle or with the lung, spontaneous biphasic contractions of the muscle as well as openings of the pneumostome with a temporal pattern characteristic of the defense reaction were observed. These findings demonstrated that the efferent pattern of the defense reaction in the snail is, to a large extent, produced by a special neuronal mechanism (the central pattern generator, CPG) triggered by the sensory input, rather than generated by ongoing processing of sensory input. The CPG consists of two components responsible for generation of two phases of the defense reaction. A characteristic feature of the CPG is that the magnitude of its response depends in a graded fashion on the strength of the initial stimulus. 2. In the pleural ganglia there are at least two electrically connected interneurons (DRN1s) that play an important role in generation of the first phase of the defense reaction. Processes of the DRN1s form a ring passing through all (except pedal and buccal) ganglia. The DRN1s received an excitatory input when a peripheral nerve was stimulated. They generated action potentials of long (0.2-2 s) duration. The DRN1 from the right ganglion was studied in more detail.(ABSTRACT TRUNCATED AT 250 WORDS)
Mechanosensory inputs to the central pattern generators for locomotion in the lamprey spinal cord: resetting, entrainment, and computer modeling
Authors: McClellan A. D. , Jang W.
Published: December 2017

Pages 2442–2454: A. D. McClellan and W. Jang, “Mechanosensory inputs to the central pattern generators for locomotion in the lamprey spinal cord: resetting, entrainment, and computer modeling.” The oscillator PRCs (Fig. 2 B) used in the computer simulations (Figs. 10—14) were inverted which was implemented by making the PRC scalars negative

See PDF for Equation

Thus synaptic inputs to an oscillator that produce phase delay (phase advance), which is represented by positive (negative) values in the PRCs in Fig. 2 B, will contribute a negative (positive) phase shift to the expression for oscillator phase ( Eq. 1) so that it takes a longer (shorter) time for the oscillator phase vector to complete one cycle.
The spatiotemporal transfer function of crayfish lamina monopolar neurons
Authors: Glantz R. M. , Bartels A.
Published: December 2017

1. The graded, synaptic potentials of first-order visual interneurons (lamina monopolar cells) were examined with intracellular recordings. The spatiotemporal properties were characterized with drifting sine wave gratings and annuli. 2. Annulus-elicited inhibition is maximal for annulus-test pulse intervals of approximately 140 ms and declines exponentially. The inhibition declines with increasing annular internal radii (ri). 3. Grating responses were examined with respect to spatial and temporal frequency. The gratings elicit sinusoidal signals that are approximately linear with contrast. 4. Variations in spatial frequency produce response functions with a low-pass or modest band-pass characteristic, which are described by a difference of Gaussians sensitivity profile. The central Gaussian approximates the sensitivity profile of photoreceptors. The inhibitory Gaussian is similar to the inhibitory field estimated with annulus pulses. The peak of the inhibitory Gaussian is approximately 18% of the peak excitatory Gaussian. 5. Variations in temporal frequency generally produce transfer functions with a band-pass characteristic and a peak at 1.0 Hz. These data were described by a difference of exponentials function convolved with a low-pass filter that approximates the photoreceptor response. The inhibitory time course estimated from these data was similar to that of the annulus measurements. 6. The spatiotemporal properties of lateral inhibition are consistent with inhibitory action by the lamina amacrine neurons. The proposed model is spatiotemporally inseparable and nonrecurrent. 7. Eleven of 20 monopolar cells tested exhibited a strong orientation preference with a bias to the vertical. Photoreceptors exhibit little or no orientation preference.
Corrigenda for Synchronization properties of spindle oscillations in a thalamic reticular nucleus model
Authors: Golomb D. , Wang X. -J. , Rinzel J.
Published: December 2017

Pages 1109–1126: D. Golomb, X.-J. Wang, and J. Rinzel, “Synchronization properties of spindle oscillations in a thalamic reticular nucleus model.” The following errors were inadvertently introduced when this article was printed. Page 1125, in the list of references, all the journal titles written as Physiol. Rev. should be Phys. Rev., and all the journal titles written as Physiol. Rev. Lett. should be Phys. Rev. Lett.
Ca(2+)-dependent Cl- conductance in taste cells from Necturus
Authors: Taylor R. , Roper S.
Published: December 2017

1. Taste responses adapt to a constant chemical stimulus. The present study describes a new ionic conductance in taste cells--a Ca(2+)-dependent anion conductance that may explain taste adaptation. 2. Patch-clamp recordings were made on isolated Necturus taste cells or on taste cells in lingual slices. When Na+ and K+ currents were eliminated with tetrodotoxin (TTX) and tetraethyl-ammonium (TEA) in the bath and replacing K+ with N-methyl-D-glucamine (NMDG+) in the pipette, Ca2+ currents were followed by prolonged outward currents. Outward current was abolished when Ca2+ was substituted with Ba2+ or when Cl- was replaced with large organic anions (methanesulfonate, isethionate, or ascorbate). 3. The outward, Ca-dependent current was reduced by certain agents that block Cl- conductances in other tissues, namely 4-acet-amido-4-isothiocyanostilbene-2,2-disulfonic acid (SITS) and 4,4-diisothiocyanostilbene-2,2-disulfonic acid (DIDS). However, other Cl- channel blockers--9-AC, furosemide and an antibody to Cl channels-had little or no specific effect on the Ca-dependent outward current in Necturus taste cells. 4. We postulate that the biological action of this Ca-dependent anion conductance in situ is to terminate depolarizing receptor potentials, even during maintained chemostimulation, thereby playing an important role in chemosensory adaptation and modulation of impulse discharge patterns in taste buds.
Multiple components of calcium current in acutely dissociated dentate gyrus granule neurons
Authors: Eliot L. S. , Johnston D.
Published: December 2017

1. Specific Ca2+ channel blocker were used to isolate and characterize different components of whole cell Ba2+ current in granule neurons acutely dissociated from guinea pig hippocampal slices. 2. Granule cell Ba2+ current peaked around +5 mV, whether elicited by step or ramp commands, and was completely blocked by 100 microM Cd2+. 3. Saturating doses (> or = 5 microM) of the dihydropyridine antagonist, nimodipine, blocked 39% of the total current, and the inhibition was partially reversible. Nimodipine had a greater effect on current at the end of a depolarizing step, suggesting some voltage dependence of its action. 4. Saturating doses (> or = 3 microM) of omega-conotoxin-GVIA irreversibly blocked 21% of the total current and did not occlude subsequent nimodipine inhibition. 5. High concentrations (> or = 100 nM) of omega-agatoxin-IVA irreversibly blocked another 20% of the total current. The effect of omega-Aga-IVA was quite slow, but saturated after several minutes at 200 nM concentration. A high dose (1 microM) produced rapid effects that were used to quantify the magnitude of block. 6. When applied together, all three blockers inhibited nearly the same amount of total current (77%) as would be expected from the sum of each blocker applied individually (80%), suggesting that the three antagonists blocked different channel types. 7. Quantitatively similar results were obtained for the effect of each blocker alone and in combination on currents elicited by depolarizing ramp commands. Ramp currents blocked by each antagonist (difference ramps) all peaked near the same potential as the initial control ramp, indicating very similar activation properties for the three current components. Difference currents elicited by step commands similarly showed little difference among the three components in their kinetics of inactivation during relatively brief (30 ms) depolarizations. With longer steps, however, the omega-CgTX-GVIA-sensitive component showed some inactivation, whereas the omega-Aga-IVA-sensitive current did not inactivate. 8. The component of current resistant to all three blockers (approximately 23% of total current) was not inhibited by omega-conotoxin-MVIIC, but was half blocked by 50 microM Ni2+. This Ni(2+)-sensitive component showed relatively rapid inactivation and peaked at a somewhat lower potential (-10 mV) than the control current. The resistant current was also inactivated by approximately 50% by holding at -60 compared with -80 mV.(ABSTRACT TRUNCATED AT 400 WORDS)
Multiple modes of activity in a model neuron suggest a novel mechanism for the effects of neuromodulators
Authors: Canavier C. C. , Baxter D. A. , Clark J. W. , Byrne J. H.
Published: December 2017

1. Previous examination of the phase space of a mathematical model of a bursting molluscan neuron has demonstrated the existence of multiple stable oscillatory modes. The present study examined the extent to which multistability could be regulated by known modulatory agents, the consequences of that regulation on the response of the neuron to synaptic inputs, the effects of noise, and the potential of multistability to enrich the repertoire of neuromodulatory effects. 2. Coexisting stable attractors may appear when a change is made in a voltage-dependent conductance in a manner that simulates the application of a neuromodulator. A small transient perturbation can shift the model neuron between stable modes, greatly amplifying the original perturbation. Thus the model becomes more sensitive to conventional synaptic inputs. These mode shifts are robust in the presence of low-amplitude synaptic noise. 3. In response to random high-amplitude synaptic noise, a model neuron rendered multistable by a simulated application of a neuromodulator produces apparently random activity, whereas in response to the same synaptic noise, a monostable model neuron produces barely perturbed regular activity. Thus an increase in the number of attractors enhances sensitivity to both conventional synaptic inputs and noise. Conversely, a decrease is associated with a reduction in sensitivity. 4. The response of a neuron to a subsequent transient perturbation in the level of neuromodulator depends on the steady-state level of the neuromodulator. For example, if the steady-state level is associated with a multistable neuron, a mode shift produced by such a transient change in the level of neuromodulator (manifested in our model as a conductance change) can persist after the conductance is returned gradually to its original value. Thus multistable dynamic activity permits the effects of a neuromodulator to persist when the neuromodulator is no longer present. 5. The mechanism of mode shifting between coexisting stable oscillatory modes introduces a number of novel possibilities with potentially profound implications for information processing and storage in a single neuron.
Glutamate metabotropic receptors increase a Ca(2+)-activated nonspecific cationic current in CA1 hippocampal neurons
Authors: Crepel V. , Aniksztejn L. , Ben-Ari Y. , Hammond C.
Published: December 2017

1. We studied the currents evoked in CA1 pyramidal neurons by the selective metabotropic glutamate receptor (mGluR) agonist 1S,3R-1-aminocyclopentane-1,3-dicarboxylate (1S,3R-ACPD; 100 microM, 2.30–5 min) with the single-electrode voltage-clamp technique in the continuous presence of tetrodotoxin (1 microM), bicuculline (10 microM), 6-cyano-7-nitroquinoxaline-2,3-dione (15 microM), and D-2-amino-5-phosphonovaleric acid (50 microM) to depress action potentials and synaptic activity. Microelectrodes were filled with 3M CsCl or 2 M Cs2SO4. 2. With CsCl-filled microelectrodes, bath application of 1S,3R-ACPD induced an inward current of -308 +/p 50 (SE) pA amplitude [holding potential (VH -60 mV, n = 12)] associated with a conductance decrease (26.5 +/- 5.6%, P < or = 0.0022, n = 12). The current-voltage (I–V) relation of the 1S,3R-ACPD-induced (difference) current investigated using ramp voltage commands from -130 to +10 mV had a V shape with two reversal potentials: -99.6 +/- 3.4 and -17.5 +/- 3.0 mV (n = 12). 3. In contrast, in the presence of external K+ channel blockers (2 mM Ba2+ and 6 mM Cs+ or 25 mM tetraethylammonium, 6 mM Cs+, and 3 mM 4-aminopyridine), 1S,3R-ACPD also generated an inward current, albeit of smaller amplitude (-114.2 +/- 27.5 pA, P < or = 0.003, VH -60 mV, n = 8). This current was associated with a conductance increase (20.7 +/- 3.1%, P < or = 0.0117, n = 8), decreased linearly with depolarization (from -130 to -60 mV), and reversed polarity at an estimated potential of -20.7 +/- 3.6 mV (n = 8). We refer to this current recorded in the presence of K+ channel blockers as IACPD. 4. In the presence of Cd2+ (200 microM, to block voltage-dependent Ca2+ channels that are readily activated in the presence of K+ channel blockers) and a low Ca2+ concentration (100 microM), IACPD decreased linearly from -130 to +10 mV and reversed polarity at -15.8 +/- 8.5 mV (n = 5).(ABSTRACT TRUNCATED AT 250 WORDS)
Compartmental models of type A and type B guinea pig medial vestibular neurons
Authors: Quadroni R. , Knopfel T.
Published: December 2017

1. We have developed compartmental models of guinea-pig medial vestibular nuclei neurons (MVNns). The structure and the parameters of the model cells were chosen to reproduce the responses of type A and type B MVNns as described in electrophysiological recordings. 2. Dynamics of membrane potentials were modeled in 46 and 61 branched electrical compartments for Type A and Type B MVNns, respectively. Each compartment was allowed to contain up to nine active ionic conductances: a fast inactivating sodium conductance, gNa, a persistent sodium conductance, gNap, a low-voltage activated calcium conductance, gCa(LVA), a high-voltage activated calcium conductance, gCa(HVA), a fast-voltage activated potassium conductance, gK(fast), a slowly relaxing voltage activated potassium conductance, gK(slow), a fast transient potassium channel, gK(A), a slowly relaxing mixed sodium-potassium conductance activating at hyperpolarized membrane potentials, gH, and a calcium-activated potassium conductance gK(AHP). The kinetics of these conductances were derived from voltage-clamp studies in a variety of preparations. Kinetic parameters as well as distribution and density of ion channels were adjusted to yield the reported electrophysiological behavior of medial vestibular neurons. 3. Dynamics of intracellular free [Ca2]i were modeled by inclusion of a Ca(2+)-pump and a Na(+)-Ca2+ exchanger for extrusion of calcium. Diffusion of calcium between submembraneous sites and the center of an electrical compartment was modeled by 25 and 6 shell-like chemical compartments for the cell body and the proximal dendrites, respectively. These compartments also contained binding sites for calcium. 4. The dynamics of active conductances were the same in both models except for gK(fast). This was necessary to achieve the different shape of spikes and of spike afterhyperpolarization in type A and type B MVNns. An intermediate depolarizing component of the spike afterhyperpolarization of type B neurons in part depended on their dendritic cable structure. 5. Variation of the low threshold calcium conductance, gCa(LVA), shows that the ability to generate low-threshold spike bursts critically depends on the density of this conductance. Sodium plateaus were generated when increasing the density of gNap. 6. The type B model cell generated rhythmic bursts of spiking activity under simulation of two distinct experimental conditions.(ABSTRACT TRUNCATED AT 400 WORDS)
Physiological correlate of fixation disengagement in the primate's frontal eye field
Authors: Dias E. C. , Bruce C. J.
Published: December 2017

1. We recorded from the frontal eye field (FEF) of rhesus monkeys while they performed the gap task in which the fixation point disappears 200 ms before the appearance of the peripheral saccadic target. This gap allows the disengagement of fixation to begin before the acquisition of saccade coordinates, thereby greatly reducing saccade latency (“gap effect”). Very short-latency saccades obtained in this gap task have been called “express saccades”. 2. We studied 145 FEF neurons that had presaccadic activity on conventional saccade tasks. When tested in the gap task with a 200-ms gap, nearly half of these neurons (69) increased their discharge rate in response to the disappearance of the fixation target. We call this increase a fixation-disengagement discharge (FDD). The mean latency of the start of the FDD relative to the fixation light extinction was 149 +/- 36 (SD) ms. 3. Gap-task trials with the saccade target in the cell's response field were randomly intermixed with trials having the target opposite to the cell's field. The FDD was present in both cases: on trials into the response field, the FDD was followed by the cell's presaccadic burst. On trials opposite the cell's field, the FDD activity was suppressed prior to the saccade. 4. The FDD was most likely to be found in cells that had the movement type of presaccadic activity, i.e., movement cells and visuomovement cells. FDD was observed in 57% of visuomovement cells A, B, and C, 50% with movement activity, and 18% purely visual.(ABSTRACT TRUNCATED AT 250 WORDS)
Depolarization-induced alkalinization (DIA) in rat hippocampal astrocytes
Authors: Pappas C. A. , Ransom B. R.
Published: December 2017

1. Depolarization of glial cells causes their intracellular pH (pHi) to increase. To more completely characterize this depolarization-induced alkalinization (DIA) in mammalian astrocytes, we studied DIA in cultured rat hippocampal astrocytes. Astrocytes were loaded with the fluorescent pH indicator 2',7'-bis(carboxyethyl)-5,6-carboxyfluorescein (BCECF), and pHi was monitored with the use of an imaging system. Cells were studied approximately 24 h after removing them from serum-containing culture medium. In HCO-3-buffered solution containing 3 mM K+, mean baseline pHi was 7.14 +/- 0.14 (mean +/- SD). 2. Astrocyte pHi rapidly and reversibly alkalinized when bath [K+] was increased from 3 to 12 mM. In HCO-3-buffered solution, mean DIA amplitude was 0.16 +/- 0.01 pH units, and mean rate of pHi change was 0.076 +/- 0.03 pH units/min. In contrast, DIA elicited in nominally HCO-3-free, N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid (HEPES)-buffered solution was much smaller (0.03 +/- 0.01 pH units, 0.04 +/- 0.01 pH units/min; P < 0.0001), indicating that DIA was, in large part, a HCO-3-dependent process. Subsequent experiments were carried out in HCO-3-buffered solution. 3. The relationship between DIA and variable changes in bath [K+] was examined. Increasing bath [K+] from 3 to 6 mM produced a DIA of 0.07 +/- 0.04 pH units, and lowering [K+] to 0.5 mM resulted in an acid shift of 0.08 +/- 0.05 pH units. The effects of these changes in [K+] on membrane potential were measured in separate experiments by whole cell patch-clamp recording. On the basis of these data, it was possible to construct a relationship between Vm and pHi; shifting membrane potential approximately 10 mV resulted in a pHi shift of approximately 0.07. 4. Application of 0.5 mM Ba2+ depolarized Vm and elicited DIA in astrocytes. This indicated that depolarization, in the absence of an increase in [K+], could cause DIA. Application of Ba2+ also blocked K(+)-induced DIA, presumably because blockade of K+ channels prevented any depolarization by K+. 5. Cells with more alkaline baseline pHis exhibited larger and more rapidly developing DIAs. The mechanism of this effect is not known. 6. The timing of serum removal affected astrocyte DIA. Cells studied approximately 24 h after serum removal always exhibited robust DIA (mean = 0.16 +/- 0.01 pH units).(ABSTRACT TRUNCATED AT 400 WORDS)
Modification of postural responses and step initiation: evidence for goal-directed postural interactions
Authors: Burleigh A. L. , Horak F. B. , Malouin F.
Published: December 2017

1. In this study, the interaction between anticipatory postural adjustments for step initiation and automatic postural responses to an external perturbation were investigated by having subjects initiate a voluntary forward step while perturbed by a backward surface translation, which caused forward sway of the body. The postural adjustments for step initiation act to move the body center of mass (COM) forward, whereas the automatic postural responses act to move the COM backward to restore stance equilibrium. Because the postural behaviors are in opposition, we asked whether a temporal hierarchy exists in which automatic postural responses are executed to restore equilibrium and followed by stereotypic postural adjustments for step initiation, or whether the interaction between these two postural behaviors is more dynamic. 2. Lower extremity electromyographs (EMGs), ground reaction forces, and kinematics were recorded from 10 subjects during three conditions: to quantify the anticipatory postural adjustments for step initiation, subjects stepped forward as soon as they felt a proprioceptive cue; to quantify the automatic postural responses to perturbation, subjects maintained stance equilibrium in response to a backward surface translation under both feet; and to quantify the interaction between the postural adjustments for the voluntary step and the automatic responses to the perturbation, subjects were exposed to a backward surface translation and instructed to step forward as soon as they felt the platform begin to move. 3. The anticipatory adjustments for step initiation included tibialis activation [stance limb = 163 +/- 28 (SE) ms; swing limb = 173 +/- 33 ms] and soleus inhibition resulting in center of foot pressure (COP) moving backward and lateral toward the swing limb to propel the COM forward over the stance limb. Subsequently, activation of the swing limb gastrocnemius resulted in heel-off. In contrast, the automatic postural adjustments for maintenance of stance equilibrium during a backward surface translation included activation of soleus and gastrocnemius (104 +/- 23 ms and 115 +/- 14 ms, respectively) resulting in a symmetrical forward displacement of the COP that moved the COM back to its original position with respect to the feet. 4. When a forward step was initiated in response to the translation, the automatic postural responses were reduced in amplitude bilaterally in soleus and in the stance limb gastrocnemius. When present the postural response occurred at the same latency when the goal was to initiate a step as when the goal was to maintain standing.(ABSTRACT TRUNCATED AT 400 WORDS)
Somatosensory effects on neurons in dorsal cochlear nucleus
Authors: Young E. D. , Nelken I. , Conley R. A.
Published: December 2017

1. Single units and evoked potentials were recorded in dorsal cochlear nucleus (DCN) in response to electrical stimulation of the somatosensory dorsal column and spinal trigeminal nuclei (together called MSN for medullary somatosensory nuclei) and for tactile somatosensory stimuli. Recordings were from paralyzed decerebrate cats. 2. DCN principal cells (type IV units) were strongly inhibited by electrical stimulation (single 50-microA bipolar pulse) in MSN or by somatosensory stimulation. Units recorded in the fusiform cell and deep layers of DCN were inhibited, suggesting that the inhibition affects both types of principal cells (i.e., both fusiform and giant cells). 3. Interneurons (type II units) that inhibit principal cells were only weakly inhibited by electrical stimulation and were never excited, demonstrating that the inhibitory effect on principal cells does not pass through the type II circuit. In the vicinity of the DCN/PVCN (posteroventral cochlear nucleus) boundary, units were encountered that were excited by electrical stimulation in MSN; some of these neurons responded to sound, and some did not. Their response properties are consistent with the hypothesis that they are deep-layer inhibitory interneurons conveying somatosensory information to the DCN. 4. Analysis of the evoked potentials produced by electrical stimulation in MSN suggests that the somatosensory inputs activate the granule cell system of the DCN molecular layer. A model based on previous work by Klee and Rall was used to show that the distribution of evoked potentials in DCN can be explained as resulting from radial currents produced in the DCN molecular and fusiform-cell layers by synchronous activation of granule cells inputs to fusiform and cartwheel cells. Current-source density analysis of the evoked potentials is consistent with this model. Thus molecular layer interneurons (cartwheel and stellate cells) are a second possible source of inhibition to principal cells. 5. With lower stimulus levels (20 microA) and pulse-pair stimuli (50- to 100-ms interstimulus interval), three components of the inhibitory response can be recognized in both fusiform cell layer and deep layer type IV units: a short-latency inhibition that begins before the start of the evoked potential; a longer-latency inhibition whose timing corresponds to the evoked potential; and an excitatory component that occurs on the rising phase of the evoked potential. The excitatory component is usually overwhelmed by the inhibitory components and could be derived from granule cell inputs; the long-latency inhibitory component could be derived from cartwheel cells or the hypothesized deep-layer inhibitory interneurons.(ABSTRACT TRUNCATED AT 400 WORDS)
Supplementary eye field contrasted with the frontal eye field during acquisition of conditional oculomotor associations
Authors: Chen L. L. , Wise S. P.
Published: December 2017

1. The companion paper reported that a substantial proportion of cells in the supplementary eye field (SEF) of macaque monkeys show significant evolution of neuronal activity as subjects learn new and arbitrary stimulus-saccade associations. The purpose of the present study was to compare and contrast the activity of the SEF and the frontal eye field (FEF) during such conditional oculomotor learning. 2. In both SEF and FEF, we observed learning-dependent and learning-selective activity, defined as significant evolution of task-related activity as monkeys learned which of four saccades was instructed by a novel stimulus. By definition, in addition to changes as the monkeys learned the instructional significance of a novel instruction stimulus, learning-dependent activity also showed task-related modulation for trials instructed by familiar stimuli, whereas learning-selective activity did not. Of the 186 SEF neurons adequately tested, 81 (44%) showed one of these two categories of learning-related change. By contrast, of the 90 FEF neurons adequately tested, only 14 (16%) showed similar properties. This difference was highly statistically significant (chi 2 = 21.1; P < 0.001). 3. We also observed persistent differences in activity for trials with familiar versus novel instruction stimuli, which we termed learning-static effects. In some cases, the learning-static effect coexisted with learning-dependent or learning-selective changes in activity, although in others it did not. In the former cases, activity changed systematically during learning, but reached a level that differed from that for familiar stimuli instructing the same saccade. In the latter cases, the activity did not change significantly as the monkey learned new conditional oculomotor associations, but did show a significant difference depending upon whether a novel or familiar stimulus instructed a given saccade. Overall, 66 of 186 (35%) cells in the SEF and 17 of 90 (19%) cells in the FEF showed learning-static effects in one or more task periods. This difference was statistically significant (chi 2 = 7.9; P < 0.005). 4. The significant difference in the properties of SEF and FEF cells suggests a functional dissociation of the two areas during conditional oculomotor learning. In this respect, the FEF resembles the primary motor cortex, whereas the SEF resembles the premotor cortex.
Innervation of motoneurons based on dendritic orientation
Authors: Rose P. K. , Jones T. , Nirula R. , Corneil T.
Published: December 2017

1. The distribution of terminals from vestibulospinal (VS) axons on the dendritic trees of neck motoneurons was determined by combining the anterograde transport of Phaseolus Vulgaris Leucoagglutinin (PHA-L) with intracellular staining techniques and three-dimensional reconstruction methods. 2. Contacts between VS axon terminals and dendrites were arranged in a nonuniform pattern that depended on the orientation (i.e., rostro-caudal vs. dorsolateral) of the dendrites. 3. This innervation pattern satisfies a critical structural condition necessary for selective nonlinear interactions between pairs of simultaneously active inputs to motoneurons.