bluuebunny/crossref_metadata_2025 huggingface dataset:
Internal Calcium Modulates Apparent Affinity of Metabotropic GABA Receptors
Authors: Shen Wen , Slaughter Malcolm M.
Published: December 2017

The metabotropic GABA receptor (GABABR) regulates calcium influx in neurons. Whole cell voltage-clamp techniques were employed to determine the effects of internal calcium on the activity of GABABRs. GABABR receptor apparent affinity was maximal when bis-( o-aminophenoxy)- N,N,N′,N′-tetraacetic acid (BAPTA) maintained internal calcium below 70 nM. Apparent affinity was reduced as internal calcium increased. EGTA did not produce similar effects, suggesting that localized increases in calcium influenced GABABR apparent affinity. Confocal imaging disclosed relatively high internal calcium just below the plasma membrane of isolated neurons. BAPTA, but not EGTA, reduced this ring of high calcium. Heparin, dantrolene, and ryanodine increased GABABR apparent affinity, effects similar to that of BAPTA. Calmodulin inhibitors also increased receptor apparent affinity. These results suggest that internally released calcium activates calmodulin, which reduces GABABR apparent affinity. This identifies a reciprocal system in which the metabotropic GABA receptor can reduce calcium influx, but internal calcium can suppress this receptor pathway. Metabotropic glutamate receptors linked to inositol 1,4,5 trisphosphate (InsP3) raised internal calcium and suppressed the action of GABABRs. Thus negative feedback systems control the balance between excitatory and inhibitory metabotropic receptor pathways in retinal neurons.
Limited Functional Grouping of Neurons in the Motor Cortex Hand Area During Individuated Finger Movements: A Cluster Analysis
Authors: Poliakov Andrew V. , Schieber Marc H.
Published: December 2017

Primary motor cortex (M1) hand area neurons show patterns of discharge across a set of individuated finger and wrist movements so diverse as to preclude classifying the neurons into functional groups on the basis of simple inspection. We therefore applied methods of cluster analysis to search M1 neuronal populations for groups of neurons with similar patterns of discharge across the set of movements. Populations from each of three monkeys showed a large group of neurons the discharge of which increased for many or all of the movements and a second small group the discharge of which decreased for many or all movements. Two to three other small groups of neurons that discharged more specifically for one or two movements also were found in each monkey, but these groups were less consistent than the groups with broad movement fields. The limited functional grouping of M1 hand area neurons suggests that M1 neurons act as a network of highly diverse elements in controlling individuated finger movements.
Cerebellar Flocculus and Paraflocculus Purkinje Cell Activity During Circular Pursuit in Monkey
Authors: Leung H.-C. , Suh M. , Kettner R. E.
Published: December 2017

Responses from 69 Purkinje cells in the flocculus and paraflocculus of two rhesus monkeys were studied during smooth pursuit of targets moving along circular trajectories and compared with responses during sinusoidal pursuit and fixation. A variety of interesting responses was observed during circular pursuit. Although some neurons fired most strongly in a single preferred direction during clockwise (CW) and counterclockwise (CCW) pursuit, others had directional preferences that changed with rotation direction. Some of these neurons showed similar modulation amplitudes during CW and CCW pursuit, whereas other neurons showed a preference for a particular rotation direction. Response specificity also was observed during sinusoidal pursuit. Some neurons showed responses that were much stronger during centrifugal pursuit, others showed a preference for centripetal pursuit, and still others showed responses during both centripetal and centrifugal motion. Differences in preferred response direction were sometimes observed for centripetal versus centrifugal pursuit. CW/CCW and centrifugal/centripetal preferences were not explained by a breakdown in component additivity. That is, modulations in firing rate during pursuit along a circular trajectory equaled the sum of modulations during horizontal and vertical sinusoidal components as well as for diagonal components. Instead all responses were well fit by a model that expressed the instantaneous firing rate of each neuron as a multilinear function of the two-dimensional position and velocity of the eye. This model generalized well to performance at different sinusoidal frequencies. It did somewhat less well for responses during fixation, suggesting some separation in the neural mechanisms of dynamic and static positioning. The model indicates that position sensitivity accounted for ∼36% of the modulation during circular pursuit, and velocity sensitivity accounted for ∼64%. When position and velocity sensitivity vectors were aligned, responses were simpler and modulations were similar during CW versus CCW pursuit. In contrast, when these vectors pointed in different directions, response complexity increased. Nonaligned position and velocity influences tended to reinforce during circular pursuit in one direction and to cancel each other during pursuit in the opposite direction. They also tended to produce response differences during centripetal versus centrifugal sinusoidal pursuit. The distinct roles played by position and velocity in shaping Purkinje cell responses are compatible with the control signals required to generate smooth pursuit along circular and other two-dimensional trajectories.
Calcium Channel Activation Facilitated by Nitric Oxide in Retinal Ganglion Cells
Authors: Hirooka Kazuyuki , Kourennyi Dmitri E. , Barnes Steven
Published: December 2017

We investigated the modulation of voltage-gated Ca channels by nitric oxide (NO) in isolated salamander retinal ganglion cells with the goals of determining the type of Ca channel affected and the signaling pathway by which modulation might occur. The NO donors, S-nitroso- N-acetyl-penicillamine (SNAP, 1 mM) and S-nitroso-cysteine (1 mM) induced modest increases in the amplitude of Ca channel currents recorded with ruptured- and permeabilized-patch techniques by causing a subpopulation of the Ca channels to activate at more negative potentials. The Ca channel antagonists ω-conotoxin GVIA and nisoldipine each reduced the Ca channel current partially, but only ω-conotoxin GVIA blocked the enhancement by SNAP. The SNAP-induced increase was blocked by oxadiazolo-quinoxaline (50 μM), suggesting that the NO generated by SNAP acts via a soluble guanylyl cyclase to raise levels of cGMP. The membrane-permeant cGMP analog 8-(4-chlorophenylthio) guanosine cyclic monophosphate also enhanced Ca channel currents and 8-bromo guanosine cyclic monophosphate (1 mM) occluded enhancement by SNAP. Consistent with these results, isobutyl-methyl-xanthine (IBMX, 10 μM), which can raise cGMP levels by inhibiting phosphodiesterase activity, increased Ca channel current by the same amount as SNAP and occluded subsequent enhancement by SNAP. Neither IBMX, the cGMP analogs, nor SNAP itself, led to activation of cGMP-gated channels. N-[2-(methylamino)ethyl]−5-isoquinoline-sulfonamide (2 μM), a broad spectrum inhibitor of protein kinase activity, KT5823 (1 μM), a specific protein kinase G (PKG) inhibitor, and a peptide inhibitor of PKG (200 μM) blocked SNAP enhancement, as did 5′-adenylylimidophosphate (1.5 mM), a nonhydrolyzable ATP analog that prevents protein phosphorylation. A peptide inhibitor of protein kinase A (10 nM) did not block the facilitory effects of SNAP. Okadaic acid (1 μM), a phosphatase inhibitor, had no effect by itself but increased the enhancement of Ca channel current by SNAP. These results suggest that NO modulates retinal ganglion cell N-type Ca channels by facilitating their voltage-dependent activation via a mechanism involving guanylyl cyclase/PKG-dependent phosphorylation. This effect could fine-tune neural integration in ganglion cells or play a role in ganglion cell disease by modulating intracellular calcium signaling.
Contributions of Ion Conductances to the Onset Responses of Octopus Cells in the Ventral Cochlear Nucleus: Simulation Results
Authors: Cai Yidao , McGee JoAnn , Walsh Edward J.
Published: December 2017

The onset response pattern displayed by octopus cells has been attributed to intrinsic membrane properties, low membrane impedance, and/or synaptic inputs. Although the importance of a low membrane impedance generally is acknowledged as an essential component, views differ on the role that ion channels play in producing the onset response. In this study, we use a computer model to investigate the contributions of ion channels to the responses of octopus cells. Simulations using current ramps indicate that, during the “ramp-up” stage, the membrane depolarizes, activating a low-threshold K+channel, K LT, which increases membrane conductance and dynamically increases the current required to evoke an action potential. As a result, the model is sensitive to the rate that membrane potential changes when initiating an action potential. Results obtained when experimentally recorded spike trains of auditory-nerve fibers served as model inputs (simulating acoustic stimulation) demonstrate that a model with K LT conductance as the dominant conductance produces realistic onset response patterns. Systematically replacing the K LT conductance by a h-type conductance (which corresponds to a hyperpolarization-activated inward rectifier current, I h) or by a leakage conductance reduces the model's sensitivity to rate of change in membrane potential, and the model's response to “acoustic stimulation” becomes more chopper-like. Increasing the h-type conductance while maintaining a large K LT conductance causes an increase in threshold to both current steps and acoustic stimulation but does not significantly affect the model's sensitivity to rate of change in membrane potential and the onset response pattern under acoustic stimulation. These findings support the idea that K LT, which is activated during depolarization, is the primary membrane conductance determining the response properties of octopus cells, and its dynamic role cannot be provided by a static membrane conductance. On the other hand, I h, which is activated during hyperpolarization, does not play a large role in the basic onset response pattern but may regulate response threshold through its contribution to the membrane conductance.
Neuronal Mechanisms for the Control of Body Orientation inClioneII. Modifications in the Activity of Postural Control System
Authors: Deliagina T. G. , Orlovsky G. N. , Selverston A. I. , Arshavsky Y. I.
Published: December 2017

The marine mollusk Clione limacina, when swimming, can stabilize different body orientations in the gravitational field. The stabilization is based on the reflexes initiated by activation of the statocyst receptor cells and mediated by the cerebro-pedal interneurons that produce excitation of the motoneurons of the effector organs; tail and wings. Here we describe changes in the reflex pathways underlying different modes of postural activity; the maintenance of the head-up orientation at low temperature, the maintenance of the head-down orientation at higher temperature, and a complete inactivation of the postural mechanisms during defense reaction. Experiments were performed on the CNS-statocyst preparation. Spike discharges in the axons of different types of neurons were recorded extracellularly while the preparation was rotated in space through 360° in different planes. We characterized the spatial zones of activity of the tail and wing motoneurons and the CPB3 interneurons mediating the effects of statocyst receptor cells on the tail motoneurons. This was done at different temperatures (10 and 20°C). The “fictive” defense reaction was evoked by electrical stimulation of the head nerve. At 10°C, a tilt of the preparation evoked activation in the tail motoneurons and wing retractor motoneurons contralateral to the tilt and in the wing locomotor motoneurons ipsilateral to the tilt. At 20°C, the responses in the tail motoneurons and in the wing retractor motoneurons occurred reversed; these neurons were now activated with the ipsilateral tilt. In the wing locomotor motoneurons the responses at 20°C were suppressed. During the defense reaction, gravitational responses in all neuron types were suppressed. Changes in the chains of tail reflexes most likely occurred at the level of connections from the statocyst receptor cells to the CPB3 interneurons. The changes in gravitational reflexes revealed in the present study are sufficient to explain the corresponding modifications of the postural behavior in Clione.
Chloride-Cotransport Blockade Desynchronizes Neuronal Discharge in the “Epileptic” Hippocampal Slice
Authors: Hochman Daryl W. , Schwartzkroin Philip A.
Published: December 2017

Antagonism of the chloride-cotransport system in hippocampal slices has been shown to block spontaneous epileptiform (i.e., hypersynchronized) discharges without diminishing excitatory synaptic transmission. Here we test the hypotheses that chloride-cotransport blockade, with furosemide or low-chloride (low-[Cl−]o) medium, desynchronizes the firing activity of neuronal populations and that this desynchronization is mediated through nonsynaptic mechanisms. Spontaneous epileptiform discharges were recorded from the CA1 and CA3 cell body layers of hippocampal slices. Treatment with low-[Cl−]o medium led to cessation of spontaneous synchronized bursting in CA1 ≥5–10 min before its disappearance from CA3. During the time that CA3 continued to burst spontaneously but CA1 was silent, electrical stimulation of the Schaffer collaterals showed that hyperexcited CA1 synaptic responses were maintained. Paired intracellular recordings from CA1 pyramidal cells showed that during low-[Cl−]otreatment, the timing of action potential discharges became desynchronized; desynchronization was identified with phase lags in firing times of action potentials between pairs of neurons as well as a with a broadening and diminution of the CA1 field amplitude. Continued exposure to low-[Cl−]o medium increased the degree of the firing-time phase shifts between pairs of CA1 pyramidal cells until the epileptiform CA1 field potential was abolished completely. Intracellular recordings during 4-aminopyridine (4-AP) treatment showed that prolonged low-[Cl−]oexposure did not diminish the frequency or amplitude of spontaneous postsynaptic potentials. CA3 antidromic responses to Schaffer collateral stimulation were not significantly affected by prolonged low-[Cl−]o exposure. In contrast to CA1, paired intracellular recordings from CA3 pyramidal cells showed that chloride-cotransport blockade did not cause a significant desynchronization of action potential firing times in the CA3 subregion at the time that CA1 synchronous discharge was blocked but did reduce the number of action potentials associated with CA3 burst discharges. These data support our hypothesis that the anti-epileptic effects of chloride-cotransport antagonism in CA1 are mediated through the desynchronization of population activity. We hypothesize that interference with Na+,K+,2Cl−cotransport results in an increase in extracellular potassium ([K+]o) that reduces the number of action potentials that are able to invade axonal arborizations and varicosities in all hippocampal subregions. This reduced efficacy of presynaptic action potential propagation ultimately leads to a reduction of synaptic drive and a desynchronization of the firing of CA1 pyramidal cells.
Motor-Unit Synchronization Increases EMG Amplitude and Decreases Force Steadiness of Simulated Contractions
Authors: Yao Wanxiang , Fuglevand Rew J. , Enoka Roger M.
Published: December 2017

The purpose of the study was to determine the effect of motor-unit synchronization on the surface electromyogram (EMG) and isometric force using a computer model of muscle contraction. The EMG and force were simulated by generating muscle fiber action potentials, defining motor-unit mechanical characteristics and territories, estimating motor-unit action potentials, specifying motor-unit discharge times, and imposing various levels of motor-unit synchronization. The output (EMG and force) was simulated at 11 levels of excitation, ranging from 5 to 100% of maximum. To synchronize motor-unit activity, selected motor-unit discharge times were adjusted; however, the number of motor units recruited and the average discharge rate of each unit was constant across synchronization conditions for a given level of excitation. Two levels of synchronization were imposed on the discharge times: a moderate and a high level, which approximated the experimentally observed range of motor-unit synchronization. The moderate level of synchrony caused the average EMG to increase by ∼65%, whereas the high level caused a 130% increase in the EMG with respect to the no-synchrony condition. Neither synchrony condition influenced the magnitude of the average force. However, motor-unit synchronization did increase the amplitude of the fluctuations in the simulated force, especially at intermediate levels of excitation. In conclusion, motor-unit synchronization increased the amplitude of the average rectified EMG and decreased the steadiness of the force exerted by the muscle in simulated contractions.
Presynaptic Calcium Channels and the Depletion of Synaptic Cleft Calcium Ions
Authors: Stanley Elis F.
Published: December 2017

The entry of calcium ions (Ca2+) through voltage-gated calcium channels is an essential step in the release of neurotransmitter at the presynaptic nerve terminal. Because the calcium channels are clustered at the release sites, the flux of Ca2+ into the terminal inevitably removes the ion from the adjacent extracellular space, the synaptic cleft. We have used the large calyx-type synapse of the chick ciliary ganglion to test for synaptic cleft Ca2+ depletion. The terminal was voltage clamped at a holding potential ( V H) of −80 mV and a depolarizing pulse was applied to a range of potentials (−60 to +60 mV). The voltage pulse activated a sustained inward calcium current and was followed, on return of the membrane potential to V H, by an inward calcium tail current. The amplitude of the tail current reflects both the number of open calcium channels at the end of the voltage pulse and the Ca2+electrochemical gradient. External barium was substituted for calcium as the charge-carrying ion because initial experiments demonstrated calcium-dependent inactivation of the presynaptic calcium channels. Tail current recruitment was compared in calyx nerve terminals that remained attached to the postsynaptic neuron and therefore retained a synaptic cleft, with terminals that had been fully isolated. In isolated terminals, the tail currents exhibited recruitment curves that could be fit by a Boltzmann distribution with a mean V 1/2 of 0.4 mV and a slope factor of 5.4. However, in attached calyces tail current recruitment was skewed to depolarized potentials with a mean V 1/2 of 11.9 mV and a slope factor of 12.0. The degree of skew of the recruitment curve in the attached calyces correlated with the amplitude of the inward current evoked by the step depolarization. The simplest interpretation of these findings is that during the depolarizing pulse Ba2+ is removed from the synaptic cleft faster than it is replenished, thus reducing the tail current by reducing the driving force for ion entry. Ca2+ depletion during presynaptic calcium channel activation is likely to be a general property of chemical transmission at fast synapses that sets a functional limit to the duration of sustained secretion. The synapse may have evolved to minimized cleft depletion by developing a calcium-efficient mechanism to gate transmitter release that requires the concurrent opening of only a few low conductance calcium channels.
Contribution of Ca2+-Permeable AMPA/KA Receptors to Glutamate-Induced Ca2+Rise in Embryonic Lumbar Motoneurons In Situ
Authors: Metzger Friedrich , Kulik Anna , Sendtner Michael , Ballanyi Klaus
Published: December 2017

Intracellular Ca2+([Ca2+]i) was fluorometrically measured with fura-2 in lumbar motoneurons of acutely isolated spinal cord slices from embryonic rats. In ester-loaded cells, bath-applied glutamate (3 μM to 1 mM) evoked a [Ca2+]iincrease by up to 250 nM that was abolished by 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) plus 2-amino-5-phosphonovalerate (APV). CNQX or APV alone reduced the response by 82 and 25%, respectively. The glutamatergic agonists kainate (KA), quisqualate (QUI), and S-α-amino-3-hydroxy-5-methyl-4-isoxalone (S-AMPA) evoked a similar [Ca2+]itransient as glutamate. N-methyl-d-aspartate (NMDA) was only effective to increase [Ca2+]iin Mg2+-free saline, whereas [1S,3R]-1-aminocyclopentane-1,3-dicarboxylic acid ([1S,3R]-ACPD) had no effect. The glutamate-induced [Ca2+]irise was suppressed in Ca2+-free superfusate. Depletion of Ca2+stores with cyclopiazonic acid (CPA) did not affect the response. Thirty-six percent of the [Ca2+]iincrease in response to membrane depolarization induced by a 50 mM K+solution persisted on combined application of the voltage-gated Ca2+channel blockers nifedipine, ω-conotoxin-GVIA and ω-agatoxin-IVA. In fura-2 dialyzed motoneurons, the glutamate-induced [Ca2+]iincrease was attenuated by ∼70% after changing from current to voltage clamp. Forty percent of the remaining [Ca2+]itransient and 20% of the concomitant inward current of 0.3 nA were blocked by Joro spider toxin-3 (JSTX). The results show that voltage-gated Ca2+channels, including a major portion of R-type channels, constitute the predominant component of glutamate-induced [Ca2+]irises. NMDA and Ca2+-permeable KA/AMPA receptors contribute about equally to the remaining component of the Ca2+rise. The results substantiate previous assumptions that Ca2+influx through JSTX-sensitive KA/AMPA receptors is involved in (trophic) signaling in developing motoneurons.
Fourier Analysis of Sinusoidally Driven Thalamocortical Relay Neurons and a Minimal Integrate-and-Fire-or-Burst Model
Authors: Smith Gregory D. , Cox Charles L. , Sherman S. Murray , Rinzel John
Published: December 2017

We performed intracellular recordings of relay neurons from the lateral geniculate nucleus of a cat thalamic slice preparation. We measured responses during both tonic and burst firing modes to sinusoidal current injection and performed Fourier analysis on these responses. For comparison, we constructed a minimal “integrate-and-fire-or-burst” (IFB) neuron model that reproduces salient features of the relay cell responses. The IFB model is constrained to quantitatively fit our Fourier analysis of experimental relay neuron responses, including: the temporal tuning of the response in both tonic and burst modes, including a finding of low-pass and sometimes broadband behavior of tonic firing and band-pass characteristics during bursting, and the generally greater linearity of tonic compared with burst responses at low frequencies. In tonic mode, both experimental and theoretical responses display a frequency-dependent transition from massively superharmonic spiking to phase-locked superharmonic spiking near 3 Hz, followed by phase-locked subharmonic spiking at higher frequencies. Subharmonic and superharmonic burst responses also were observed experimentally. Characterizing the response properties of the “tuned” IFB model leads to insights regarding the observed stimulus dependence of burst versus tonic response mode in relay neurons. Furthermore the simplicity of the IFB model makes it a candidate for large scale network simulations of thalamic functioning.
Chronic Recording of Regenerating VIIIth Nerve Axons With a Sieve Electrode
Authors: Mensinger Allen F. , Anderson David J. , Buchko Christopher J. , Johnson Michael A. , Martin David C. , Tresco Patrick A. , Silver Robert B. , Highstein Stephen M.
Published: December 2017

A micromachined silicon substrate sieve electrode was implanted within transected toadfish ( Opsanus tau) otolith nerves. High fidelity, single unit neural activity was recorded from seven alert and unrestrained fish 30 to 60 days after implantation. Fibrous coatings of genetically engineered bioactive protein polymers and nerve guide tubes increased the number of axons regenerating through the electrode pores when compared with controls. Sieve electrodes have potential as permanent interfaces to the nervous system and to bridge missing connections between severed or damaged nerves and muscles. Recorded impulses might also be amplified and used to control prosthetic devices.
Mapping of IP3-Mediated Ca2+ Signals in Single Human Neuroblastoma SH-SY5Y Cells: Cell Volume Shaping the Ca2+ Signal
Authors: van Acker K. , Bautmans B. , Bultynck G. , Maes K. , Weidema A. F. , de Smet P. , Parys J. B. , de Smedt H. , Missiaen L. , Callewaert G.
Published: December 2017

Fast confocal laser-scanning microscopy was used to study spatiotemporal properties of IP3-mediated Ca2+ release signals in human SH-SY5Y neuroblastoma cells. [Ca2+]iincreases were not affected by ryanodine (30 μM) or caffeine (10 mM) and largely insensitive to removal of external Ca2+, indicating predominance of IP3-induced Ca2+release. Ca2+ signals evoked by high concentration (10 μM) of the muscarinic agonist carbachol appeared as self-propagating waves initiating in cell processes. At low carbachol concentrations (500 nM) Ca2+ changes in most cells displayed striking spatiotemporal heterogeneity. The Ca2+ response in the cell body was delayed and had a smaller amplitude and a slower rise time than that in processes. Ca2+ changes in processes either occurred in a homogeneous manner throughout the whole process or were sometimes confined to hot spots. Regional differences in surface-to-volume ratio appear to be critical clues that determine the spatiotemporal pattern of intracellular Ca2+ release signals.
Lateralized Tinnitus Studied With Functional Magnetic Resonance Imaging: Abnormal Inferior Colliculus Activation
Authors: Melcher J. R. , Sigalovsky I. S. , Guinan J. J. , Levine R. A.
Published: December 2017

Tinnitus, the perception of sound in the absence of external stimuli, is a common and often disturbing symptom that is not understood physiologically. This paper presents an approach for using functional magnetic resonance imaging (fMRI) to investigate the physiology of tinnitus and demonstrates that the approach is effective in revealing tinnitus-related abnormalities in brain function. Our approach as applied here included 1) using a masking noise stimulus to change tinnitus loudness and examining the inferior colliculus (IC) for corresponding changes in activity, 2) separately considering subpopulations with particular tinnitus characteristics, in this case tinnitus lateralized to one ear, 3) controlling for intersubject differences in hearing loss by considering only subjects with normal or near-normal audiograms, and 4) tailoring the experimental design to the characteristics of the tinnitus subpopulation under study. For lateralized tinnitus subjects, we hypothesized that sound-evoked activation would be abnormally asymmetric because of the asymmetry of the tinnitus percept. This was tested using two reference groups for comparison: nontinnitus subjects and nonlateralized tinnitus subjects. Binaural noise produced abnormally asymmetric IC activation in every lateralized tinnitus subject ( n = 4). In reference subjects ( n = 9), activation (i.e., percent change in image signal) in the right versus left IC did not differ significantly. Compared with reference subjects, lateralized tinnitus subjects showed abnormally low percent signal change in the IC contralateral, but not ipsilateral, to the tinnitus percept. Consequently, activation asymmetry (i.e., the ratio of percent signal change in the IC ipsilateral versus contralateral to the tinnitus percept) was significantly greater in lateralized tinnitus subjects as compared with reference subjects. Monaural noise also produced abnormally asymmetric IC activation in lateralized tinnitus subjects. Two possible models are presented to explain why IC activation was abnormally low contralateral to the tinnitus percept in lateralized tinnitus subjects. Both assume that the percept is associated with abnormally high (“tinnitus-related”) neural activity in the contralateral IC. Additionally, they assume that either 1) additional activity evoked by sound was limited by saturation or 2) sound stimulation reduced the level of tinnitus-related activity as it reduced the loudness of (i.e., masked) the tinnitus percept. In summary, this work demonstrates that fMRI can provide objective measures of lateralized tinnitus and tinnitus-related activation can be interpreted at a neural level.
Control of Cricket Stridulation by a Command Neuron: Efficacy Depends on the Behavioral State
Authors: Hedwig Berthold
Published: December 2017

Crickets use different song patterns for acoustic communication. The stridulatory pattern-generating networks are housed within the thoracic ganglia but are controlled by the brain. This descending control of stridulation was identified by intracellular recordings and stainings of brain neurons. Its impact on the generation of calling song was analyzed both in resting and stridulating crickets and during cercal wind stimulation, which impaired the stridulatory movements and caused transient silencing reactions. A descending interneuron in the brain serves as a command neuron for calling-song stridulation. The neuron has a dorsal soma position, anterior dendritic processes, and an axon that descends in the contralateral connective. The neuron is present in each side of the CNS. It is not activated in resting crickets. Intracellular depolarization of the interneuron so that its spike frequency is increased to 60–80 spikes/s reliably elicits calling-song stridulation. The spike frequency is modulated slightly in the chirp cycle with the maximum activity in phase with each chirp. There is a high positive correlation between the chirp repetition rate and the interneuron's spike frequency. Only a very weak correlation, however, exists between the syllable repetition rate and the interneuron activity. The effectiveness of the command neuron depends on the activity state of the cricket. In resting crickets, experimentally evoked short bursts of action potentials elicit only incomplete calling-song chirps. In crickets that previously had stridulated during the experiment, short elicitation of interneuron activity can trigger sustained calling songs during which the interneuron exhibits a spike frequency of ∼30 spikes/s. During sustained calling songs, the command neuron activity is necessary to maintain the stridulatory behavior. Inhibition of the interneuron stops stridulation. A transient increase in the spike frequency of the interneuron speeds up the chirp rate and thereby resets the timing of the chirp pattern generator. The interneuron also is excited by cercal wind stimulation. Cercal wind stimulation can impair the pattern of chirp and syllable generation, but these changes are not reflected in the discharge pattern of the command neuron. During wind-evoked silencing reactions, the activity of the calling-song command neuron remains unchanged, but under these conditions, its activity is no longer sufficient to maintain stridulation. Therefore stridulation can be suppressed by cercal inputs from the terminal ganglia without directly inhibiting the descending command activity.
Effects of Attention on MT and MST Neuronal Activity During Pursuit Initiation
Authors: Recanzone Gregg H. , Wurtz Robert H.
Published: December 2017

The responses of neurons in monkey extrastriate areas MT (middle temporal) and MST (medial superior temporal), and the initial metrics of saccadic and pursuit eye movements, have previously been shown to be better predicted by vector averaging or winner-take-all models depending on the stimulus conditions. To investigate the potential influences of attention on the neuronal activity, we measured the responses of single MT and MST neurons under identical stimulus conditions when one of two moving stimuli was the target for a pursuit eye movement. We found the greatest attentional modulation across neurons when two stimuli moved through the receptive field (RF) of the neuron and the stimulus motion was initiated at least 450 ms before reaching the center of the RF. These conditions were the same as those in which a winner-take-all model better predicted both the eye movements and the underlying neuronal activity. The modulation was almost always an increase of activity, and it was about equally frequent in MT and MST. A modulation of >50% was observed in ∼41% of MT neurons and 27% of MST neurons. Responses to all directions of motion were modulated so that the direction tuning curves in the attended and unattended conditions were similar. Changes in the background activity with target selection were small and unlikely to account for the observed attentional modulation. In contrast, there was little change in the neuronal response with attention when the stimulus reached the RF center 150 ms after motion onset, which was also the condition in which the vector average model better predicted the initial eye movements and the activity of the neurons. These results are consistent with a competition model of attention in which top-down attention acts on the activity of one of two competing populations of neurons activated by the bottom-up input from peripheral stimuli. They suggest that there is a minimal separation of the populations necessary before attention can act on one population, similar to that required to produce a winner-take-all mode of behavior in pursuit initiation. The present experiments also suggest that it takes several hundred milliseconds to develop this top-down attention effect.
2-Deoxyglucose–Induced Long-Term Potentiation of Monosynaptic IPSPs in CA1 Hippocampal Neurons
Authors: Krnjević Krešimir , Zhao Yong-Tao
Published: December 2017

In previous experiments on excitatory synaptic transmission in CA1, temporary (10–20 min) replacement of glucose with 10 mM 2-deoxyglucose (2-DG) consistently caused a marked and very sustained potentiation (2-DG LTP). To find out whether 2-DG has a similar effect on inhibitory synapses, we recorded pharmacologically isolated mononosynaptic inhibitory postsynaptic potentials (IPSPs; under current clamp) and inhibitory postsynaptic currents (IPSCs; under voltage clamp); 2-DG was applied both in the presence and the absence of antagonists of N-methyl-d-aspartate (NMDA). In spite of sharply varied results (some neurons showing large potentiation, lasting for >1 h, and many little or none), overall there was a significant and similar potentiation of IPSP conductance, both for the early (at ≈30 ms) and later (at ≈140 ms) components of IPSPs or IPSCs: by 35.1 ± 10.25% (mean ± SE; for n = 24, P = 0.0023) and 36.5 ± 16.3% (for n = 19, P = 0.038), respectively. The similar potentiation of the early and late IPSP points to a presynaptic mechanism of LTP. Overall, the LTP was statistically significant only when 2-DG was applied in the absence of glutamate antagonists. Tetanic stimulations (in presence or absence of glutamate antagonists) only depressed IPSPs (by half). In conclusion, although smaller and more variable, 2-DG–induced LTP of inhibitory synapses appears to be broadly similar to the 2-DG–induced LTP of excitatory postsynaptic potentials previously observed in CA1.
Sacrocaudal Afferents Induce Rhythmic Efferent Bursting in Isolated Spinal Cords of Neonatal Rats
Authors: Lev-Tov A. , Delvolvé I. , Kremer E.
Published: December 2017

The ability of mammalian spinal cords to generate rhythmic motor behavior in nonlimb moving segments was examined in isolated spinal cords of neonatal rats. Stimulation of sacrocaudal afferents (SCA) induced alternating left-right bursts in lumbosacral efferents and in tail muscles. On each side of the tail, flexors, extensors, and abductors were coactive during each cycle of activity. This rhythm originated mainly in the sacrocaudal region because it persisted in sacrocaudal segments after surgical removal of the thoracolumbar cord. Sacrocaudal commissural pathways were sufficient to maintain the left-right alternation of lumbar efferent bursts, because their timing was unaltered after a complete thoracolumbar hemisection. The lumbar rhythm originated in part from sacrocaudal activity ascending in lateral and ventrolateral funiculi, because efferent bursts in rostral lumbar segments were nearly abolished on a particular side by lesions of the lateral quadrant of the cord at the L4–L5 junction. Intracellular recordings from S2–S3 motoneurons, obtained during the rhythm, revealed the presence of phasic oscillations of membrane potential superimposed on a tonic depolarization. Bursts of spikes occurred on the depolarizing phases of the oscillation. Between these bursts the membrane input conductance increased, and hyperpolarizing drive potentials were revealed. The inhibitory drive and the decreased input resistance coincided with contralateral efferent bursts, suggesting that crossed pathways controlled it. Our studies indicate that pattern generators are not restricted to limb-moving spinal segments and suggest that regional specializations of pattern-generating circuitry and their associated interneurons are responsible for the different motor patterns produced by the mammalian spinal cord.
Impairments in Prehension Produced by Early Postnatal Sensory Motor Cortex Activity Blockade
Authors: Martin John H. , Donarummo Laura , Hacking Antony
Published: December 2017

This study examined the effects of blocking neural activity in sensory motor cortex during early postnatal development on prehension. We infused muscimol, either unilaterally or bilaterally, into the sensory motor cortex of cats to block activity continuously between postnatal weeks 3–7. After stopping infusion, we trained animals to reach and grasp a cube of meat and tested behavior thereafter. Animals that had not received muscimol infusion (unilateral saline infusion; age-matched) reached for the meat accurately with small end-point errors. They grasped the meat using coordinated digit flexion followed by forearm supination on 82.7% of trials. Performance using either limb did not differ significantly. In animals receiving unilateral muscimol infusion, reaching and grasping using the limb ipsilateral to the infusion were similar to controls. The limb contralateral to infusion showed significant increases in systematic and variable reaching end-point errors, often requiring subsequent corrective movements to contact the meat. Grasping occurred on only 14.8% of trials, replaced on most trials by raking without distal movements. Compensatory adjustments in reach length and angle, to maintain end-point accuracy as movements were started from a more lateral position, were less effective using the contralateral limb than ipsilateral limb. With bilateral inactivations, the form of reaching and grasping impairments was identical to that produced by unilateral inactivation, but the magnitude of the reaching impairments was less. We discuss these results in terms of the differential effects of unilateral and bilateral inactivation on corticospinal tract development. We also investigated the degree to which these prehension impairments after unilateral blockade reflect control by each hemisphere. In animals that had received unilateral blockade between postnatal weeks (PWs) 3 and 7, we silenced on-going activity (after PW 11) during task performance using continuous muscimol infusion. We inactivated the right (previously active) and then the left (previously silenced) sensory motor cortex. Inactivation of the ipsilateral (right) sensory motor cortex produced a further increase in systematic error and less frequent normal grasping. Reinactivation of the contralateral (left) cortex produced larger increases in reaching and grasping impairments than those produced by ipsilateral inactivation. This suggests that the impaired limb receives bilateral sensory motor cortex control but that control by the contralateral (initially silenced) cortex predominates. Our data are consistent with the hypothesis that the normal development of skilled motor behavior requires activity in sensory motor cortex during early postnatal life.
HERG-Like Potassium Current Regulates the Resting Membrane Potential in Glomus Cells of the Rabbit Carotid Body
Authors: Overholt Jeffrey L. , Ficker Eckhard , Yang Tianen , Shams Hashim , Bright Gary R. , Prabhakar Nanduri R.
Published: December 2017

Direct evidence for a specific K+ channel underlying the resting membrane potential in glomus cells of the carotid body has been absent. The product of the human ether-a-go-go–related gene (HERG) produces inward rectifier currents that are known to contribute to the resting membrane potential in other neuronal cells. The goal of the present study was to determine whether carotid body glomus cells express HERG-like K+ current, and if so, to determine whether a HERG-like current regulates the resting membrane potential. Freshly dissociated rabbit glomus cells under whole cell voltage clamp exhibited slowly decaying outward currents that activated 20–30 mV positive to the resting membrane potential. Raising extracellular K+revealed a slowly deactivating inward tail current indicative of HERG-like K+ current. HERG-like currents were not found in cells resembling type II cells. The HERG-like current was blocked by dofetilide (DOF) in a concentration-dependent manner (IC50 = 13 ± 4 nM, mean ± SE) and high concentrations of Ba2+ (1 and 10 mM). The biophysical and pharmacological characteristics of this inward tail current suggest that it is conducted by a HERG-like channel. The steady-state activation properties of the HERG-like current ( V h = −44 ± 2 mV) suggest that it is active at the resting membrane potential in glomus cells. In whole cell, current-clamped glomus cells (average resting membrane potential, − 48 ± 4 mV), DOF, but not tetraethylammonium, caused a significant (13 mV) depolarizing shift in the resting membrane potential. Using fluorescence imaging, DOF increased [Ca2+]i in isolated glomus cells. In an in-vitro carotid body preparation, DOF increased basal sensory discharge in the carotid sinus nerve in a concentration-dependent manner. These results demonstrate that glomus cells express a HERG-like current that is active at, and responsible for controlling the resting membrane potential.
Outputs of Radula Mechanoafferent Neurons inAplysiaare Modulated by Motor Neurons, Interneurons, and Sensory Neurons
Authors: Rosen Steven C. , Miller Mark W. , Cropper Elizabeth C. , Kupfermann Irving
Published: December 2017

The gain of sensory inputs into the nervous system can be modulated so that the nature and intensity of afferent input is variable. Sometimes the variability is a function of other sensory inputs or of the state of motor systems that generate behavior. A form of sensory modulation was investigated in the Aplysiafeeding system at the level of a radula mechanoafferent neuron (B21) that provides chemical synaptic input to a group of motor neurons (B8a/b, B15) that control closure and retraction movements of the radula, a food grasping structure. B21 has been shown to receive both excitatory and inhibitory synaptic inputs from a variety of neuron types. The current study investigated the morphological basis of these heterosynaptic inputs, whether the inputs could serve to modulate the chemical synaptic outputs of B21, and whether the neurons producing the heterosynaptic inputs were periodically active during feeding motor programs that might modulate B21 outputs in a phase-specific manner. Four cell types making monosynaptic connections to B21 were found capable of heterosynaptically modulating the chemical synaptic output of B21 to motor neurons B8a and B15. These included the following: 1) other sensory neurons, e.g., B22; 2) interneurons, e.g., B19; 3) motor neurons, e.g., B82; and 4) multifunction neurons that have sensory, motor, and interneuronal functions, e.g., B4/5. Each cell type was phasically active in one or more feeding motor programs driven by command-like interneurons, including an egestive motor program driven by CBI-1 and an ingestive motor program driven by CBI-2. Moreover, the phase of activity differed for each of the modulator cells. During the motor programs, shifts in B21 membrane potential were related to the activity patterns of some of the modulator cells. Inhibitory chemical synapses mediated the modulation produced by B4/5, whereas excitatory and/or electrical synapses were involved in the other instances. The data indicate that modulation is due to block of action potential invasion into synaptic release regions or to alterations of transmitter release as a function of the presynaptic membrane potential. The results indicate that just as the motor system of Aplysia can be modulated by intrinsic mechanisms that can enhance its efficiency, the properties of primary sensory cells can be modified by diverse inputs from mediating circuitry. Such modulation could serve to optimize sensory cells for the different roles they might play.
Attention to Both Space and Feature Modulates Neuronal Responses in Macaque Area V4
Authors: McAdams Carrie J. , Maunsell John H. R.
Published: December 2017

Attention is the mechanism with which we select specific aspects of our environment for processing. Psychological experiments have shown that attention can be directed to a spatial location or to a particular object. Electrophysiological studies in trained macaque monkeys have found that attention can strengthen the responses of neurons in cortical area V4. Some of these studies have attributed these effects to spatial attention, whereas others have suggested that feature-directed attention may modulate the neuronal response. Here we report that neuronal correlates for both spatial and feature-directed attention exist in individual neurons in area V4 of behaving rhesus monkeys.
Light-Evoked Responses of Bipolar Cells in a Mammalian Retina
Authors: Euler Thomas , Masland Richard H.
Published: December 2017

We recorded light-evoked responses from rod and cone bipolar cells using patch-clamp techniques in a slice preparation of the rat retina. Rod bipolar cells responded to light with a sustained depolarization (on response) followed at light offset by a slight hyperpolarization. on and off cone bipolar cells were encountered, both with diverse temporal properties. The responses of rod bipolar cells were composed primarily of two components, a nonspecific cation current and a chloride current. The chloride current was reduced greatly in axotomized cells and could be suppressed by coapplication of the GABAA antagonist bicuculline and the GABAC antagonist (1,2,5,6-tetrahydropyridine-4-yl)methylphosphinic acid. This suggests that it largely reflects feedback from GABAergic amacrine cells. The response latency of intact rod bipolar cells was shorter than that of the axotomized cells, and the sensitivity curve covered more than twice the dynamic range. Application of the GABA receptor antagonists partially mimicked the effects of axotomy. These findings suggest that functional properties of the axon terminal system—notably synaptic feedback from amacrine cells—play an important role in defining the response properties of mammalian bipolar cells.