bluuebunny/crossref_metadata_2025 huggingface dataset:
Origins of the power law relation between movement velocity and curvature: modeling the effects of muscle mechanics and limb dynamics
Authors: Gribble P. L. , Ostry D. J.
Published: December 2017

1. When subjects trace patterns such as ellipses, the instantaneous velocity of movements is related to the instantaneous curvature of the trajectories according to a power law-movements tend to slow down when curvature is high and speed up when curvature is low. It has been proposed that this relationship is centrally planned. 2. The arm's muscle properties and dynamics can significantly affect kinematics. Even under isometric conditions, muscle mechanical properties can affect the development of muscle forces and torques. Without a model that accounts for these effects, it is difficult to distinguish between kinematic patterns that are attributable to central control and patterns that arise because of dynamics and muscle properties and are not represented in the underlying control signals. 3. In this paper we address the nature of the control signals that underlie movements that obey the power law. We use a numerical simulation of arm movement control based on the lambda version of the equilibrium point hypothesis. We demonstrate that simulated elliptical and circular movements, and elliptical force trajectories generated under isometric conditions, obey the power law even though there was no relation between curvature and speed in the modeled control signals. 4. We suggest that limb dynamics and muscle mechanics-specifically, the springlike properties of muscles-can contribute significantly to the emergence of the power law relationship in kinematics. Thus, without a model that accounts for these effects, care must be taken when making inferences about the nature of neural control.
Adaptation of primate vestibuloocular reflex to altered peripheral vestibular inputs. I. Frequency-specific recovery of horizontal VOR after inactivation of the lateral semicircular canals
Authors: Angelaki D. E. , Hess B. J. , Arai Y. , Suzuki J.
Published: December 2017

1. The adaptive plasticity of the vestibuloocular reflex (VOR) following a selective lesion of the peripheral vestibular organs was investigated in rhesus monkeys whose lateral semicircular canals were inactivated by plugging of the canal lumen in both ears. Gain and phase of horizontal, vertical, and torsional slow-phase eye velocity were determined from three-dimensional eye movement recordings obtained acutely after the plugging operation, as well as in regular intervals up to 10 mo later. 2. Acutely after plugging, horizontal VOR was minimal during yaw rotation with gains of < 0.1 at all frequencies. Horizontal VOR gain gradually increased over time, reaching gains of 0.4–0.5 for yaw oscillations at 1.1 Hz approximately 5 mo after lateral canal inactivation. This response recovery was strongly frequency dependent: horizontal VOR gains were largest at the highest frequency tested and progressively decreased for lower frequencies. Below approximately 0.1 Hz, no consistent horizontal VOR could be elicited even 10 mo after plugging. 3. The frequency-dependent changes in gain paralleled changes in horizontal VOR phase. Below approximately 0.1–0.05 Hz large phase leads were present, similarly as in semicircular canal primary afferents. Smaller phase leads were also present at higher frequencies, particularly at 1.1 Hz (the highest frequency tested). 4. Consistent with the afferent-like dynamics of the adapted horizontal VOR, per- and postrotatory horizontal responses to constant-velocity yaw rotations were short lasting. Time constants of the slow-phase eye velocity envelope of the horizontal postrotatory nystagmus were approximately 2 s. Nonetheless, a consistent horizontal optokinetic afternystagmus was evoked in plugged animals. 5. A torsional component that was absent in intact animals was consistently present during yaw rotation acutely after lateral canal inactivation and remained approximately constant thereafter. The frequency response characteristics of this torsional component resembled those of the adapted horizontal slow-phase responses: gain decreased and large phase leads were introduced at frequencies below approximately 0.05–0.1 Hz. Torsional responses elicited by roll oscillations in supine position, on the other hand, were indistinguishable in their dynamics from intact animals. No consistent vertical nystagmus was elicited during yaw rotation. 6. Our results show that there is a slow, frequency-specific recovery of horizontal VOR after selective inactivation of the lateral semicircular canals. Both the spatial organization and the dynamic properties of the adapted VOR responses are distinctly different from responses in intact animals, suggesting complex changes in the underlying vestibuloocular circuitry.
Hyperexcitability of entorhinal cortex and hippocampus after application of aminooxyacetic acid (AOAA) to layer III of the rat medial entorhinal cortex in vitro
Authors: Scharfman H. E.
Published: December 2017

1. Injection of aminooxyacetic acid (AOAA) into the entorhinal cortex in vivo produces acute seizures and cell loss in medial entorhinal cortex. To understand these effects, AOAA was applied directly to the medial entorhinal cortex in slices containing both the entorhinal cortex and hippocampus. Extracellular and intracellular recordings were made in both the entorhinal cortex and hippocampus to study responses to angular bundle stimulation and spontaneous activity. 2. AOAA was applied focally by leak from a micropipette or by pressure ejection. Evoked potentials increased gradually within 5 min of application, particularly the late, negative components. Evoked potentials continued to increase for up to 1 h, and these changes persisted for the remainder of the experiment (up to 5 h after drug application). 3. Paired pulse facilitation (100-ms interval) was also enhanced after AOAA application. Increasing stimulus frequency to 1-10 Hz increased evoked potentials further, and after several seconds of such stimulation multiple field potentials occurred. When stimulation was stopped at this point, repetitive field potentials occurred spontaneously for 1-2 min. These recordings, and simultaneous extracellular recordings in different layers, indicated that spontaneous synchronous activity occurred in entorhinal neurons. Intracellularly labeled cortical pyramidal cells depolarized and discharged during spontaneous and evoked field potentials. 4. The effects of AOAA were blocked reversibly by bath application of the N-methyl-D-aspartate (NMDA) receptor antagonist D-amino-5-phosphonovalerate (D-APV; 25 microM) or focal application of D-APV to the medial entorhinal cortex. 5. Simultaneous extracellular recordings from the entorhinal cortex and hippocampus demonstrated that spontaneous synchronous activity in layer III was often followed within several milliseconds by negative field potentials in the terminal zones of the perforant path (stratum moleculare of the dentate gyrus and stratum lacunosum-moleculare of area CA1). The extracellular potentials recorded in the dentate gyrus corresponded to excitatory postsynaptic potentials and action potentials in dentate granule cells. However, extracellular potentials in area CA1 were small and rarely correlated with discharge in CA1 pyramidal cells. 6. The results demonstrate that AOAA application leads to an NMDA-receptor-dependent enhancement of evoked potentials in medial entorhinal cortical neurons, which appears to be irreversible. The potentials can be facilitated by repetitive stimulation, and lead to synchronized discharges of entorhinal neurons. The discharges invade other areas such as the hippocampus, indicating how seizure activity may spread after AOAA injection in vivo. These data suggest that AOAA may be a useful tool to study longlasting changes in NMDA receptor function that lead to epileptiform activity and neurodegeneration.
Metabotropic glutamate receptor agonist-induced hyperpolarizations in rat basolateral amygdala neurons: receptor characterization and ion channels
Authors: Holmes K. H. , Keele N. B. , Arvanov V. L. , Shinnick-Gallagher P.
Published: December 2017

1. Metabotropic glutamate receptor (mGluR)-agonist-induced hyperpolarizations and corresponding outward currents were analyzed in basolateral amygdala (BLA) neurons in rat brain slice preparations with current-clamp and single-electrode voltage-clamp recording to characterize the mGluR subtype(s) and the ion channel(s) mediating this response. 2. The mGluR agonist (1S,3R)-1-amino-cyclopentane-1,3-dicarboxylic acid (1S,3R-ACPD) induced a membrane hyperpolarization or outward current in BLA neurons in a concentration-dependent manner (median effective concentration = 34 microM; range = 10-200 microM); the 1S,3R-ACPD hyperpolarizations are recorded in 89% of neurons that accommodate or cease firing in response to a 400-ms depolarizing current injection (0.5 nA). 3. mGluR agonists elicited hyperpolarizations or outward currents in a concentration-dependent manner in the following rank order of potency: (2S,3S,4S)-alpha-(carboxycyclopropyl)glycine (L-CCG-I) > 1S,3R-ACPD > (s)-4-carboxyphenylglycine = (RS)-4-carboxy-3-hydroxyphenylglycine (4C3HPG) > L-aminophosphonobutyric acid > (1S,3S)-1-amino-cyclopentane-1,3-dicarboxylic acid. In contrast, the mGluR agonists quisqualate and ibotenate induced only depolarizations in the presence of D-2-amino-5-phosphonovalerate and 6-cyano-7-nitroquinoxaline-2,3-dione in BLA neurons. 4. The 1S,3R-ACPD-induced outward current is mediated through a large-conductance calcium-dependent potassium (BK) conductance. The BK channel blockers iberiotoxin and charybdotoxin blocked the response, as did the potassium channel blockers tetraethylammonium and 4-aminopyridine; the small-conductance calcium-activated potassium channel blocker apamin did not affect the response. 5. The mGluR-agonist-induced hyperpolarization is blocked in amygdala slices from animals pretreated with pertussis toxin (PTX). 1S,3R-ACPD hyperpolarizations were recorded in neurons contralateral but not ipsilateral to the site of PTX injection. 6. The antagonist (+/-)-alpha-methyl-4-carboxyphenylglycine (MCPG, 500 microM) reduced significantly the 1S,3R-ACPD-induced hyperpolarization. 7. In conclusion, the relative potency of L-CCG-I and 4C3HPG in evoking only hyperpolarizations (outward currents) in accommodating neurons, and the observation that MCPG (500 microM) reduces the hyperpolarization, suggest that a group-II-like mGluR underlies the hyperpolarizing response. The mGluR-induced response is sensitive to iberiotoxin and to pretreatment with PTX, suggesting activation of BK channels through a group II mGluR linked to a PTX-sensitive G protein in BLA neurons.
Serotonergic modulation of evoked responses in turtle cerebellar Purkinje cells
Authors: Lu H. , Larson-Prior L. J.
Published: December 2017

1. Immunocytochemical studies of the turtle brain revealed the presence of serotonin (5-hydroxytryptamine, 5-HT) immunoreactive (5-HT-ir) processes in the granule and Purkinje cell layers, but not in the molecular layer (ML), of the cerebellar cortex. Immunoreactive axonal profiles were present throughout the granule cell layer (GCL) where they generally coursed in an anteroposterior direction and could frequently be seen to ascend toward the Purkinje cell layer (PCL). Occasional 5-HT-ir processes were observed adjacent to Purkinje cell somata. 2. The effects of exogenously applied serotonin on mossy fiber and parallel fiber evoked responses in turtle Purkinje cells were examined by use of intrasomatic and intradendritic recordings in an intact cerebellar preparation in vitro. 3. Bath application of serotonin (0.2–1.0 microM) produced a dose-dependent reduction in Purkinje cell membrane resistance, which was not correlated with changes in postsynaptic response amplitude. At 5-HT concentrations > 1.0 microM (0.01–5 mM), resistance values returned to control levels. No consistent changes in spike width or postspike afterhyperpolarization were seen in response to serotonin application, nor were endogenous pacemaker-like discharges affected. Firing rate, assessed as threshold response to depolarizing current injection (0.3–1.0 nA, 1 s duration), was increased in 51% and decreased in 40% of cells tested. 4. Single stimuli delivered to either the cerebellar peduncle or the GCL resulted in the activation of fast excitatory postsynaptic potentials (fEPSP). These responses were dose dependently reduced in amplitude by bath application of serotonin (0.2–1.0 microM). At concentrations ranging from 10 to 100 microM, the response amplitude following agonist application plateaued at approximately 70% of control value. With higher dose applications (0.5-5 mM) of serotonin, the response amplitude exhibited a steep reduction (from 65-10% of control value). 5. Brief trains of stimuli (5 stimuli, 50 Hz) delivered to either the cerebellar peduncle or the GCL resulted in the activation of slow excitatory postsynaptic potentials (sEPSP). The peak amplitude of this response was unaffected by bath application of serotonin at concentrations ranging from 0.2 to 100 microM. At higher concentrations (0.5–5 mM), the sEPSP peak amplitude was dose-dependently reduced, with the largest amplitude reduction seen after peduncular stimulation. 6. It is suggested that serotonin acts as a modulator of fast excitatory synaptic activity in the cerebellar cortex, while exerting little affect on slow excitatory events. The fact that serotonin preferentially affects fast excitatory transmission may have important implications for the integration of incoming sensory signals at both the granule and Purkinje cell level.
Cd(2+)-induced injury in CNS white matter
Authors: Fern R. , Black J. A. , Ransom B. R. , Waxman S. G.
Published: December 2017

1. The affect of extracellular Cd2+ on CNS white matter was studied using an isolated rat optic nerve preparation. A 100-min exposure to 200 microM Cd2+ reduced the area of the compound action potential (CAP) recorded from the optic nerve to 32.6 +/- 3.8% (mean +/- SE) of the preexposure area, compared with a reduction to 74.9 +/- 2.9% after 100 min in control conditions (P > 0.001). This CAP reduction was not reversed after 120 min of reperfusion with Cd(2+)-free solution, or by perfusion with Cd2+ chelators. 2. Cd(2+)-induced CAP loss occurred in the absence of extracellular Ca2+. Increasing extracellular Ca2+ concentration to 16 mM, however, prevented Cd(2+)-induced CAP loss. Once evident, Cd(2+)-induced CAP reduction could not subsequently be reversed by addition of 16 mM Ca2+. 3. Low concentrations of Cd2+ (60 microM) did not significantly reduce CAP area. This concentration of Cd2+ combined with high extracellular K+ (30 mM) caused CAP loss that was blocked by 10 microM nifedipine, an antagonist of L-type voltage-gated Ca2+ channels. 4. Treatment with pharmacological inhibitors of membrane proteins known to be inhibited by Cd2+ did not affect the CAP. These included inhibitors of voltage-gated Ca2+ channels, Ca(2+)-activated K+ channels, Ca(2+)-ATPase and the Na+/Ca2+ exchanger. 5. Treatment with pharmacological agents that inhibit calmodulin or disrupt tubulin, two intracellular proteins affected by Cd2+, did not affect CAP area. 6. The effect of Cd2+ was not prevented by pretreatment with (+)-cyanidanol-3, an agent that prevents Cd(2+)-induced lipid peroxidation. 7. Treatment with antimycin A, a inhibitor of mitochondrial respiration, resulted in irreversible CAP reduction with a time course and extent similar to that produced by 200 microM Cd2+. Cd(2+)-induced CAP reduction was prevented by 1 mM cysteine, which prevents Cd(2+)-induced disruption of mitochondrial respiration. 8. The ultrastructure of optic nerves exposed to 200 microM Cd2+ for 100 min was characterized by swollen mitochondria with disrupted cristae and dissolution of microtubules, which were replaced by flocculent debris. Occasional regions of axonal swelling and empty spaces beneath the myelin also were found. Qualitatively similar changes in mitochondria and cytoskeletal elements were found in optic nerves exposed to antimycin A for 100 min. Astrocytes also displayed disrupted mitochondria and had an electron-lucent appearance under both conditions. 9. The neurological injury produced by exposure to Cd2+ is characterized by lesions of CNS white matter. Our results indicate that Cd(2+)-induced white matter injury in vitro results largely from disruption of mitochondrial respiration after Cd2+ influx through routes that include voltage-gated Ca2+ channels.
Smooth pursuitlike eye movements evoked by microstimulation in macaque nucleus reticularis tegmenti pontis
Authors: Yamada T. , Suzuki D. A. , Yee R. D.
Published: December 2017

1. Smooth pursuitlike eye movements were evoked with low current microstimulation delivered to rostral portions of the nucleus reticularis tegmenti pontis (rNRTP) in alert macaques. Microstimulation sites were selected by the observation of modulations in single-cell firing rates that were correlated with periodic smoothpursuit eye movements. Current intensities ranged from 10 to 120 microA and were routinely < 40 microA. Microstimulation was delivered either in the dark with no fixation, 100 ms after a fixation target was extinguished, or during maintained fixation of a stationary or moving target. Evoked eye movements also were studied under open-loop conditions with the target image stabilized on the retina. 2. Eye movements evoked in the absence of a target rapidly accelerated to a constant velocity that was maintained for the duration of the microstimulation. Evoked eye speeds ranged from 3.7 to 23 deg/s and averaged 11 deg/s. Evoked eye speed appeared to be linearly related to initial eye position with a sensitivity to initial eye position that averaged 0.23 deg.s-1.deg-1. While some horizontal and oblique smooth eye movements were elicited, microstimulation resulted in upward eye movements in 89% of the sites. 3. Evoked eye speed was found to be dependent on microstimulation pulse frequency and current intensity. Within limits, evoked eye speed increased with increases in stimulation frequency or current intensity. For stimulation frequencies < 300–400 Hz, only smooth pursuit-like eye movements were evoked. At higher stimulation frequencies, accompanying saccades consistently were elicited. 4. Feedback of retinal image motion interacted with the evoked eye movements to decrease eye speed if the visual motion was in the opposite direction as the evoked, pursuit-like eye movements. 5. The results implicate rNRTP as part of the neuronal substrate that controls smooth-pursuit eye movements. NRTP appears to be divided functionally into a rostral, pursuit-related portion and a caudal, saccade-related area. rNRTP is a component of a corticopontocerebellar circuit that presumably involves the pursuit area of the frontal eye field and that parallels the middle and medial superior temporal cerebral cortical/dorsalateral pontine nucleus (MT/MST-DLPN-cerebellum) pathway known to be involved also with regulating smooth-pursuit eye movements.
Dihydropyridine-sensitive, voltage-gated Ca2+ channels contribute to the resting intracellular Ca2+ concentration of hippocampal CA1 pyramidal neurons
Authors: Magee J. C. , Avery R. B. , Christie B. R. , Johnston D.
Published: December 2017

1. Whole cell recordings and high-speed fluorescence imaging were used to investigate the contribution of voltage-gated Ca2+ channels to the resting Ca2+ concentration ([Ca2+]i) in hippocampal CA1 pyramidal neurons. 2. Prolonged membrane hyperpolarization produced, in a voltage-dependent manner, sustained decreases in [Ca2+]i in the somatic and apical dendritic regions of the neuron. This hyperpolarization-induced decrease in [Ca2+]i occurred with a time constant of approximately 1 s and was maintained for as long as the membrane potential was held at the new level. Ratiometric measures showed that [Ca2+]i is significantly elevated at holding potentials of -50 mV compared with -80 mV. 3. The hyperpolarization-induced decrease in [Ca2+]i was reduced significantly by 200 microM Cd2+ and 10 microM nimodipine, but was only slightly inhibited by 50 microM Ni2+. The largest amplitude decrease in [Ca2+]i was observed in the proximal apical dendrites with the amplitude of the Ca2+ change decreasing with further distance from the soma. 4. Whole cell recordings from acutely isolated hippocampal pyramidal neurons reveal a slowly inactivating Ca2+ current with similar voltage dependence and pharmacology to the hyperpolarization-induced decrease in [Ca2+]i. 5. The data suggest that a population of dihydropyridine-sensitive Ca2+ channels are active at resting membrane potentials and that this channel activation significantly contributes to the resting [Ca2+]i. These channels appear to be present throughout the neuron and may be located most densely in the proximal apical dendrites.
Analysis of dynamic spectra in ferret primary auditory cortex. I. Characteristics of single-unit responses to moving ripple spectra
Authors: Kowalski N. , Depireux D. A. , Shamma S. A.
Published: December 2017

1. Auditory stimuli referred to as moving ripples are used to characterize the responses of both single and multiple units in the ferret primary auditory cortex. Moving ripples are broadband complex sounds with a sinusoidal spectral profile that drift along the logarithmic frequency axis at a constant velocity. 2. Neuronal responses to moving ripples are locked to the phase of the ripple, i.e., they exhibit the same periodicity as that of the moving ripple profile. Neural responses are characterized as a function of ripple velocity (temporal property) and ripple frequency (spectral property). Transfer functions describing the response to these temporal and spectral modulations are constructed. Temporal transfer functions are inverse Fourier transformed to obtain impulse response functions that reflect the cell's temporal characteristics. Ripple transfer functions are inverse Fourier transformed to obtain the response field, a measure analogous to the cell's response area. These operations assume linearity in the cell's response to moving ripples. 3. Transfer functions and other response functions are shown to be fairly independent on the overall level or depth of modulation of the ripple stimuli. Only downward moving ripples were used in this study. 4. The temporal and ripple transfer functions are found to be separable, in that their shapes remain unchanged for different test parameters. Thus ripple transfer functions and response fields remain statistically similar in shape (to within an overall scale factor) regardless of the ripple velocity or whether stationary or moving ripples are used in the measurement. The same stability in shape holds for the temporal transfer functions and the impulse response functions measured with different ripple frequencies. Separability implies that the combined spectrotemporal transfer function of a cell can be written as the product of a purely ripple and a purely temporal transfer functions, and thus that the neuron can be computationally modeled as processing spectral and temporal information in two separate and successive stages. 5. The ripple parameters that characterize cortical cells are distributed somewhat evenly, with the characteristic ripple frequencies ranging from 0.2 to > 2 cycles/octave and the characteristic angular frequency typically ranging from 2 to 20 Hz. 6. Many responses exhibit periodicities in the spectral envelope of the stimulus. These periodicities are of two types. Slow rebounds, not found in the spectral envelope, and with a period of approximately 150 ms, appear with various strengths in approximately 30% of the cells. Fast regular firings with interspike intervals of approximately 10 ms are much less common and appear to correspond to interactions between the component tones that make up a ripple.
Equivalence of amplified current flowing from dendrite to soma measured by alteration of repetitive firing and by voltage clamp in layer 5 pyramidal neurons
Authors: Schwindt P. , Crill W.
Published: December 2017

1. Plots of steady firing rate versus injected current (f-I relations) were constructed from intrasomatic injected current pulses applied alone (control relations) and together with dendritic glutamate iontophoresis (test relations) at sites on the distal apical dendrite 185–555 microns from the soma in layer 5 pyramidal neurons from rat cortex studied in a brain slice. The test f-I relations exhibited a parallel shift along the current axis, and the slopes of the control and test relations differed by < 10% in most neurons. This behavior indicates that constant injected current and steady glutaminergic dendritic input evoke equivalent steady-state repetitive firing in a neuron with active dendrites. The parallel shift of the f-I curves allowed us to compute the amplitude of axial current arriving in the soma from the apical dendrite during repetitive firing. 2. We compared the transmitted current computed from the f-I curve shift with that measured by somatic voltage clamp during the same iontophoresis. When measured during voltage clamp at different somatic membrane potentials, the transmitted current increased with somatic depolarization (was amplified) in most cells, an observation inconsistent with passive dendrites. This larger-amplitude current closely predicted the transmitted current computed from the f-I curve shift, whereas the smaller transmitted current measured at resting potential did not. A set of control experiments indicated that these different predictions were well within the measurement error associated with computation of transmitted current based on f-I curve shifts. The action of blocking agents confirmed that the depolarizing amplification depended on tetrodotoxin (TTX)- and D-2-amino-5-phosphonopentoic acid (APV)-sensitive dendritic channels. 3. The agreement of two independent measurements (somatic voltage clamp and f-I curve shift) of the axial current transmitted from dendrite to soma indicates that the amplification of transmitted current observed in voltage clamp occurs physiologically. We discuss the usefulness of the effective current concept for determining synaptic weighting in network models of neurons with active dendrites.
Presynaptic depression of excitatory synaptic inputs to rat hypoglossal motoneurons by muscarinic M2 receptors
Authors: Bellingham M. C. , Berger A. J.
Published: December 2017

1. Whole cell recordings of glutamatergic excitatory postsynaptic currents (EPSCs) evoked by electrical stimulation in the reticular formation were made from visualized hypoglossal motoneurons (HMs) in rat brain stem slices. 2. Carbachol, muscarine, or physostigmine reduced EPSC amplitude to 50 +/- 3%, 37 +/- 3%, and 54 +/- 7% (mean +/- SE) of control, respectively; effects of carbachol and physostigmine were antagonized by atropine (1–2 microM). EPSC depression was most effectively antagonized by methoctramine, an M2 muscarinic acetylcholine receptor (mAChR) antagonist with a high affinity constant (pKB) of 8.07 for the receptor mediating this response, whereas pirenzepine, an M1 mAChR antagonist, had a pKB of < 7.0, showing that EPSC depression was mediated by the M2 mAChR. 3. Postsynaptic properties of HMs (holding current and input resistance), EPSCs (reversal potential, rise time, half-width, and decay time constant), and postsynaptic glutamate-gated currents (amplitude and waveform) were not altered by carbachol or muscarine. 4. Muscarine did not decrease presynaptic neuron excitability, because the frequency of spontaneous EPSCs in HMs in the absence of tetrodotoxin (TTX) was either unchanged or increased. Leak and action currents of reticular formation neurons were not significantly altered by muscarine. In contrast, with TTX present, the frequency of spontaneous miniature glutamatergic EPSCs in HMs was decreased by both carbachol (mean change = 203 +/- 46%) and muscarine (mean change = 185 +/- 26%), with no change in miniature EPSC amplitude distribution. 5. Muscarinic depression of excitatory transmission to HMs thus occurs at the presynaptic terminal, most probably affecting release mechanisms downstream from calcium entry, and is likely to be significant during rapid eye movement sleep, possibly underlying the loss of tongue tone and inspiratory activity during this state.
Differential involvement of group II and group III mGluRs as autoreceptors at lateral and medial perforant path synapses
Authors: Macek T. A. , Winder D. G. , Gereau R. W. , Ladd C. O. , Conn P. J.
Published: December 2017

1. Previous reports have shown that group III metabotropic glutamate receptors (mGluRs) serve as autoreceptors at the lateral perforant path, but to date there has been no rigorous determination of the roles of other mGluRs as autoreceptors at this synapse. Furthermore, it is not known which of the mGluR subtypes serve as autoreceptors at the medial perforant path synapse. With the use of whole cell patch-clamp and field excitatory postsynaptic potential (fEPSP) recording techniques, we examined the groups of mGluRs that act as autoreceptors at lateral and medial perforant path synapses in adult rat hippocampal slices. 2. Consistent with previous reports, the group III mGluR agonist (D,L)-2-amino-4-phosphonobutyric acid reduced fEPSPs and excitatory postsynaptic currents (EPSCs) in the dentate gyrus. However, the group-II-selective agonist (2S,1'R,2'R,3'R)-2-(2,3-dicarboxycyclopropyl)glycine (DCG-IV) also reduced fEPSPs and EPSCs, suggesting that multiple mGluR subtypes may serve as autoreceptors at perforant path synapses. 3. Selective activation of either medial or lateral perforant pathways revealed that micromolar concentrations of (L)-2-amino-4-phosphonobutyric acid (L-AP4) reduce fEPSPs in lateral but not medial perforant path, suggesting group III involvement at the lateral perforant pathway. Conversely, DCG-IV and 2R, 4R-4-aminopyrrolidine-2,4-dicarboxylate, another group-II-selective mGluR agonist, potently reduced fEPSPs at the medial but not lateral perforant path, suggesting that a group II mGluR may act as an autoreceptor at the medial perforant path-dentate gyrus synapse. 4. Antagonist studies with group-selective antagonists such as (2S,3S,4S)-2-methyl-2-(carboxycyclpropyl)glycine (MCCG; group II) and alpha-methyl-L-AP4 (MAP4; group III) suggest differential involvement of each group at these synapses. The effect of L-AP4 at the lateral perforant path synapse was blocked by MAP-4, but not MCCG. In contrast, the effect of DCG-IV was blocked by application of MCCG, but not MAP4. 5. Previous studies suggest that the effect of L-AP4 at the lateral perforant path synapse is mediated by a presynaptic mechanism. In the present studies, we found that concentrations of DCG-IV that reduce transmission at the medial perforant path synapse reduce paired-pulse depression and do not reduce kainate-evoked currents recorded from dentate granule cells. This is consistent with the hypothesis that DCG-IV also acts by a presynaptic mechanism.
Variability of extracellular spike waveforms of cortical neurons
Authors: Fee M. S. , Mitra P. P. , Kleinfeld D.
Published: December 2017

1. Here we study the variability in extracellular records of action potentials. Our work is motivated, in part, by the need to construct effective algorithms to classify single-unit waveforms from multiunit recordings. 2. We used microwire electrode pairs (stereotrodes) to record from primary somatosensory cortex of awake, behaving rat. Our data consist of continuous records of extracellular activity and segmented records of extracellular spikes. Spectral and principal component techniques are used to analyze mean single-unit wave-forms, the variability between different instances of a single-unit waveform, and the underlying background activity. 3. The spectrum of the variability between different instances of a single-unit waveforms is not white, and falls off above 1 kHz with a frequency dependence of roughly f-2. This spectrum is different from that of the mean spike waveforms, which falls off roughly as f-4, but is essentially identical with the spectrum of background activity. The spatial coherence of the variability on the 10-micron scale also falls off at high frequencies. 4. The variability between different instances of a single-unit waveform is dominated by a relatively small number of principal components. As a consequence, there is a large anisotropy in the cluster of the spike waveforms. 5. The background noise cannot be represented as a stationary Gaussian random process. In particular, we observed that the spectrum changes significantly between successive 20-ms intervals. Furthermore, the total power in the background activity exhibits larger fluctuations than is consistent with a stationary Gaussian random process. 6. Roughly half of the single-unit spike waveforms exhibit systematic changes as a function of the interspike interval. Although this results in a non-Gaussian distribution in the space of waveforms, the distribution can be modeled by a scalar function of the interspike interval. 7. We use a set of 44 mean single-unit waveforms to define the space of differences between spike waveforms. This characterization, together with that of the background activity, is used to construct a filter that optimizes the detection of differences between single-unit waveforms. Further, an information theoretic measure is defined that characterizes the detectability.
Activation of pharmacologically distinct metabotropic glutamate receptors depresses reticulospinal-evoked monosynaptic EPSPs in the lamprey spinal cord
Authors: Krieger P. , el Manira A. , Grillner S.
Published: December 2017

1. Different metabotropic glutamate receptors (mGluRs) can modulate synaptic transmission in different regions in the CNS, but their roles at individual synaptic connections have not been detailed. We used paired intracellular recordings from reticulospinal axons and their postsynaptic target neurons in the lamprey spinal cord to investigate the effects of mGluR activation on glutamatergic synaptic transmission. 2. The mGluR agonists (1S,3R)-1-aminocyclopentane-1,3-dicarboxyylic acid [(1S,3R)-ACPD] and L(+)-2-amino-4-phosphonobutyric acid (L-AP4) both reduced the amplitude of monosynaptic excitatory postsynaptic potentials (EPSPs) elicited by stimulation of single reticulospinal axons. The depression of monosynaptic unitary EPSPs occurred without any apparent change in the input resistance of postsynaptic neurons. Furthermore, the mGluR agonists did not affect the amplitude of (RS)-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-induced depolarizations. Taken together, these results thus suggest that (1S,3R)-ACPD and L-AP4 depress reticulospinal synaptic transmission via presynaptic mechanisms. 3. (2S,1'S,2'S)-2-(carboxycyclopropyl) glycine (L-CCG-I), which selectively activates group II mGluRs, also reduced the amplitude of reticulospinal-evoked EPSPs without any apparent change in the input resistance or membrane potential of the postsynaptic neuron. 4. The mGluR antagonist alpha-methyl-L-AP4 blocked the depression induced by L-AP4 but not that induced by (1S,3R)-ACPD. Furthermore, the effects of coapplication of (1S,3R)-ACPD and L-AP4 were additive, suggesting that they inhibit synaptic transmission by an action on pharmacologically distinct mGluRs. 5. These results provide evidence for the colocalization of at least two different subtypes of presynaptic mGluRs on a single reticulospinal axon in the lamprey. These presynaptic mGluRs could serve as glutamatergic autoreceptors limiting the extent of reticulospinal-mediated excitation of spinal neurons.
Functional parasagittal compartments in the rat cerebellar cortex: an in vivo optical imaging study using neutral red
Authors: Chen G. , Hanson C. L. , Ebner T. J.
Published: December 2017

1. The spatial patterns of activation in the rat cerebellar cortex evoked by peripheral stimulation were studied in vivo using optical imaging techniques. 2. Crus I and Crus II were stained with the pH sensitive dye, neutral red. Electrical stimulation of the vibrissae area of the ipsilateral face evoked optical responses consisting of parasagittal bands. The bands were 100–300 microns in width, elongated in the anterior-posterior direction, commonly extended across at least two folia, and varied in number from 1 to 7. 3. The optical responses were dependent on activation of postsynaptic elements since they were decreased substantially by the non-N-methyl-D-aspartate antagonist, 6-cyano-7-nitroquinoxaline-2,3-dione. The optical bands were shown to correspond anatomically with the parasagittal compartments revealed by immunostaining with anti-zebrin II. 4. The present study demonstrates that functional parasagittal compartments exist in the rat cerebellar cortex and suggests that zebrin-positive Purkinje cell subgroups are anatomically related to this functional organization.
Initiation of saccades during fixation or pursuit: evidence in humans for a single mechanism
Authors: Krauzlis R. J. , Miles F. A.
Published: December 2017

1. In four human subjects, we measured the latency of saccadic eye movements made to a second, eccentric target after an initial, foveated target was extinguished. In separate interleaved trails, the targets were either both stationary (“fixation”) or both moving with the same velocity (“pursuit”). For both fixation and pursuit trials, we extinguished the first target at randomized times during maintained fixation or pursuit and varied the time interval (“gap duration”) before the appearance of the second target. 2. During both fixation and pursuit, the presence of a 200-ms gap reduced the latencies of saccades, compared with those obtained with no gap. For two subjects, we imposed additional, intermediate gap durations and found that saccade latencies varied as a function of gap duration. Furthermore, the latencies of saccades elicited during pursuit displayed the same dependence on gap duration as those elicited during fixation. 3. Our results demonstrate that the “gap effect” observed for saccades made during fixation also occurs for saccades made during pursuit. To the extent that the gap effect on saccade latency reflects a mechanism underlying the release of fixation, our results suggest that the same mechanism is invoked for saccades made during pursuit. From the viewpoint of initiating saccades, the existence of separate fixation and pursuit systems may be irrelevant.
Two types of BK channels in immature rat neocortical pyramidal neurons
Authors: Kang J. , Huguenard J. R. , Prince D. A.
Published: December 2017

1. The properties of large conductance Ca(2+)-activated K+ channels (BK channels) were investigaed in neocortical infragranular pyramidal neurons by the use of inside-out patch recordings. Neurons were acutely isolated from slices of newborn to 28-day-old rats (P0-P28) by using minimal protease exposure followed by trituration with a vibrating glass probe. Two types of BK channels, slow-gating and fast-gating, were observed in immature neurons (P0-P5), whereas only slow-gating BK were found in more mature neurons. Fast-gating BK channels differed in conductance, voltage dependence, and kinetics from the slow-gating ones. 2. The properties of fast-gating channels included a conductance of 145 +/- 12.9 (SE) pS; frequent openings with short mean open times that were relatively voltage-independent, mean closed times that showed a voltage-dependent increase, a voltage-dependent decrease in open probability (Po). The properties of slow-gating channels contrasted with those of the fast-gating ones, in that the former had a conductance of 181 +/- 3.9 pS, longer mean open times that showed a voltage-dependent increase, mean closed times that showed a marked voltage-dependent decrease, a voltage-dependent increase in Po, and slight inward rectification. The significance of these developmental variations in channel properties is discussed.
In Vivo Responses of Single Olfactory Receptor Neurons of Channel Catfish to Binary Mixtures of Amino Acids
Authors: Kang Jiesheng , Caprio John
Published: December 2017

Kang, Jiesheng and John Caprio. In vivo response of single olfactory receptor neurons of channel catfish to binary mixtures of amino acids. J. Neurophysiol. 77: 1–8, 1997. For the first time in any vertebrate, in vivo responses of single olfactory receptor neurons to odorant mixtures were studied quantitatively. Extracellular electrophysiological response of 54 single olfactory receptor neurons from 23 channel catfish, Ictalurus punctatus, to binary mixtures of amino acids and to their components were recorded simultaneously with the electroolfactogram (EOG). For 57% (73 of 128) of the tests, no significant change (N) from spontaneous activity occurred. Responses to the remaining 55 tests of binary mixtures were excitatory (E; 13%) or suppressive (S; 30%). No response type was associated with any specific mixture across the neurons sampled. Eighty-six percent of the responses of catfish olfactory receptor neurons to binary mixtures were classifed similar to at least one of the component responses, a percentage comparable (i.e., 89%) with that observed for single olfactory bulb neurons in the same species to equivalent binary mixtures. The responses of single olfactory receptor neurons to component-similar binary mixtures (i.e., component responses were both E, both S, and both N, respectively) were generally (80% of 59 tests) classified similar to the responses to the components. For E+N and S+N binary mixtures, the N component often (66% of 58 tests) reduced or concealed (i.e., “masked”) the excitatory and suppressive responses, respectively. For the majority (6 of 11 tests) of E+S binary mixtures, null activity resulted. Responses to the remaining five tests were either excitatory ( n = 3) or suppressive ( n = 2).
Effects of Prenatal Cocaine Exposure on the Developing Hippocampus: Intrinsic and Synaptic Physiology
Authors: Baraban Scott C. , Schwartzkroin Philip A.
Published: December 2017

Baraban, Scott and Philip A. Schwartzkroin. Effects of prenatal cocaine exposure on the developing hippocampus: intrinsic and synaptic physiology. J. Neurophysiol. 77: 126–136, 1977. A variety of neurological complications has been reported in infants exposed to cocaine during gestation. In the present study, intrinsic cell properties of hippocampal neurons from CA1, CA3, and dentate gyrus regions were measured and compared in tissue from neonatal rats exposed to saline or cocaine in utero. Synaptic properties of the CA1 pyramidal cell region were analyzed at postnatal day (P) 20 with the use of extracellular and intracellular recording techniques. In vitro intracellular recordings ( n = 223) obtained at P10, P15 and P20 in tissue from cocaine- and saline-exposed animals revealed no differences in standard cell properties such as resting membrane potential, input resistance, time constant, and action potential amplitude or duration. Hippocampal slices from cocaine-exposed animals exhibited a marked reduction of spike frequency adaptation for all three types of principal hippocampal neurons (e.g., CA1, CA3, and granule cells). The amplitudes of afterhyperpolarizations following a spike train were also decreased in CA1 and CA3 cells in tissue from cocaine-exposed animals. Extracellular and intracellular recordings in the CA1 pyramidal cell region at P20 were obtained to assess and compare synaptic function in tissue from cocaine- and saline-exposed animals. In hippocampal slices from cocaine-exposed animals, synaptic responses in the CA1 region were characterized by multiple population spike activity and reduced inhibitory postsynaptic potentials. The reduction in fast inhibitory postsynaptic potential conductance was not associated with a change in reversal potential. These results suggest that gestational cocaine exposure induces significant changes in intrinsic and synaptic electrophysiological properties of hippocampal neurons in the developing animal. The cell and synaptic features are consistent with an increase in hippocampal excitability, which may contribute to the neurobehavioral deficits and epileptogenic predisposition reported in this infant population. As such, this in utero drug exposure model may provide a useful system in which to elucidate and study the basic cellular mechanisms underlying neurological complications associated with maternal cocaine abuse.
Periodic Microstimulation of Single Mechanoreceptive Afferents Produces Frequency-Following Responses in Human EEG
Authors: Kelly Edward F. , Trulsson Mats , Folger Stephen E.
Published: December 2017

Kelly, Edward F., Mats Trulsson, and Stephen E. Folger. Periodic microstimulation of single mechanoreceptive afferents produces frequency-following responses in human EEG. J. Neurophysiol. 77: 137–144, 1997. Dense multichannel recordings of scalp electroencephalogram were obtained in the vicinity of primary somatosensory cortex, time-locked to repetitive train microstimulation of single, physiologically characterized skin mechanoreceptive afferents in the median nerve of a single human subject. Frequency-domain analysis of cross-trial averages for fast-adapting type one and slowly adapting type one afferents revealed prominent, topographically organized “driving” responses in the electroencephalogram at the frequency of stimulation, which vanished under various statistical and experimental control conditions. The responses also exhibited systematic declines in amplitude both across and within trials, and orderly changes in scalp topography as a function of the location of afferents' receptive fields on the hand. The observed response properties are tentatively explained in terms of characteristics of the pattern of afferent drive impressed on the cortex by microstimulation.
Ca2+Currents in Central Insect Neurons: Electrophysiological and Pharmacological Properties
Authors: Wicher Dieter , Penzlin Heinz
Published: December 2017

Wicher, Dieter, and Heinz Penzlin. Ca2+currents in central insect neurons: electrophysiological and pharmacological properties. J. Neurophysiol. 77: 186–199, 1997. Ca2+currents in dorsal unpaired median (DUM) neurons isolated from the fifth abdominal ganglion of the cockroach Periplaneta americana were investigated with the whole cell patch-clamp technique. On the basis of kinetic and pharmacological properties, two different Ca2+currents were separated in these cells: mid/low-voltage-activated (M-LVA) currents and high-voltage-activated (HVA) currents. M-LVA currents had an activation threshold of −50 mV and reached maximal peak values at −10 mV. They were sensitive to depolarized holding potentials and decayed very rapidly. The decay was largely Ca2+dependent. M-LVA currents were effectively blocked by Cd2+median inhibiting concentration (IC50= 9 μM), but they also had a remarkable sensitivity to Ni2+(IC50= 19 μM). M-LVA currents were insensitive to vertebrate LVA channel blockers like flunarizine and amiloride. The currents were, however, potently blocked by ω-conotoxin MVIIC (1 μM) and ω-agatoxin IVA (50 nM). The blocking effects of ω-toxins developed fast (time constant τ = 15 s) and were fully reversible after wash. HVA currents activated positive to −30 mV and showed maximal peak currents at +10 mV. They were resistant to depolarized holding potentials up to −50 mV and decayed in a less pronounced manner than M-LVA currents. HVA currents were potently blocked by Cd2+(IC50= 5 μM) but less affected by Ni2+(IC50= 40 μM). These currents were reduced by phenylalkylamines like verapamil (10 μM) and benzothiazepines like diltiazem (10 μM), but they were insensitive to dihydropyridines like nifedipine (10 μM) and BAY K 8644 (10 μM). Furthermore, HVA currents were sensitive to ω-conotoxin GVIA (1 μM). The toxin-induced reduction of currents appeared slowly (τ ∼ 120 s) and the recovery after wash was incomplete in most cases. The dihydropyridine insensitivity of the phenylalkylamine-sensitive HVA currents is a property the cockroach DUM cells share with other invertebrate neurons. Compared with Ca2+currents in vertebrates, the DUM neuron currents differ considerably from the presently known types. Although there are some similarities concerning kinetics, the pharmacological profile of the cockroach Ca2+currents especially is very different from profiles already described for vertebrate currents.