bluuebunny/crossref_metadata_2025 huggingface dataset:
Linear and Nonlinear Spectral Integration in Type IV Neurons of the Dorsal Cochlear Nucleus. II. Predicting Responses With the Use of Nonlinear Models
Authors: Nelken Israel , Kim Peter J. , Young Eric D.
Published: December 2017

Nelken, Israel, Peter J. Kim, and Eric D. Young. Linear and nonlinear spectral integration in type IV neurons of the dorsal cochlear nucleus. II. Predicting responses with the use of nonlinear models. J. Neurophysiol. 78: 800–811, 1997. Two nonlinear modeling methods were used to characterize the input/output relationships of type IV units, which are one principal cell type in the dorsal cochlear nucleus (DCN). In both cases, the goal was to derive predictive models, i.e., models that could predict the responses to other stimuli. In one method, frequency integration was estimated from response maps derived from single tones and simultaneous pairs of tones presented over a range of frequencies. This model combined linear integration of energy across frequency and nonlinear interactions of energy at different frequencies. The model was used to predict responses to noisebands with varying width and center frequency. In almost all cases, predictions using two-tone interactions were better than linear predictions based on single-tone responses only. In about half the cases, reasonable quantitative fits were achieved. The fits were best for noisebands with narrow bandwidth and low sound levels. In the second nonlinear method, the spectrotemporal receptive field (STRF) was derived from responses to broadband stimuli. The STRF could account for some qualitative features of the responses to broad noisebands and spectral notches embedded in broad noisebands. Quantitatively, however, the STRFs failed to predict the responses of type IV units even to simple broadband noise stimuli. For narrowband stimuli, the STRF failed to predict even qualitative features (such as excitatory and inhibitory frequency bands). The responses of DCN type IV units presumably result from interactions of two inhibitory sources, a strong one that is preferentially activated by narrowband stimuli and a weaker one that is preferentially activated by broadband stimuli. The results presented here suggest that the STRF measures effects related to the broadband inhibition, whereas two-tone interactions measure mostly effects related to narrowband inhibition. This explains why models based on two-tone interactions predict the responses to narrow noisebands much better then models based on STRFs. It is concluded that a minimal stimulus set for characterizing type IV units must contain both broadband and narrowband stimuli, because each stimulus class by itself activates only partially the integration mechanisms that shape the responses of type IV units. Similar conclusions are expected to hold in other parts of the auditory system: when characterizing a complex auditory unit, it is necessary to use a range of stimuli to ensure that all integration mechanisms are activated.
Activity-Dependent [Ca2+]i Changes in Guinea Pig Vagal Motoneurons: Relationship to the Slow Afterhyperpolarization
Authors: Lasser-Ross Nechama , Ross William N. , Yarom Yosef
Published: December 2017

Lasser-Ross, Nechama, William N. Ross, and Yosef Yarom. Activity-dependent [Ca2+]i changes in guinea pig vagal motoneurons: relationship to the slow afterhyperpolarization. J. Neurophysiol. 78: 825–834, 1997. Vagal motoneurons in slices from the guinea-pig brain stem were injected with the fluorescent [Ca2+]i indicators fura-2, furaptra, or Calcium Green-1. Spike-induced fluorescence changes were measured in the soma and dendrites and simultaneously the long-lasting afterhyperpolarization was recorded with a sharp microelectrode in the soma. Na+ spikes or Ca2+ spikes increased [Ca2+]i (measured as a change in indicator fluorescence) in all locations in the soma and dendrites. Each spike in a train of action potentials caused a step increase in fluorescence of about equal amplitude when nonsaturating indicators were used. Peak changes at all locations occurred at the time of the last action potential. Transients measured with low concentrations of Calcium Green-1 or furaptra had a recovery time constant of ∼500–1,500 ms in the cell body. The recovery time course was faster in the dendrites than in the soma. The norepinephrine-sensitive, slow afterhyperpolarization (sAHP) had a time to peak of ∼800 ms and a recovery time constant of 2–5 s, much longer than the recovery time course of the fluorescence changes. Some of these experiments were repeated on pyramidal neurons from the CA1 region of the rat hippocampus with similar results. In both cell types, the data suggest that the time course of neither the rising phase nor the falling phase of the sAHP, nor the underlying conductance, directly reflects the time course of the [Ca2+]i change. The mechanism connecting the parameters remains unclear. One possibility is that an additional second messenger system is involved.
Characteristics of Temporal Summation of Second Pain Sensations Elicited by Brief Contact of Glabrous Skin by a Preheated Thermode
Authors: Vierck Charles J. , Cannon Richard L. , Fry Gentry , Maixner William , Whitsel Barry L.
Published: December 2017

Vierck, Charles J., Jr., Richard L. Cannon, Gentry Fry, William Maixner, and Barry L. Whitsel. Characteristics of temporal summation of second pain sensations elicited by brief contact of glabrous skin by a preheated thermode. J. Neurophysiol. 78: 992–1002, 1997. Temporal summation of sensory intensity was investigated in normal subjects using novel methods of thermal stimulation. A Peltier thermode was heated and then applied in a series of brief (700 ms) contacts to different sites on the glabrous skin of either hand. Repetitive contacts on the thenar or hypothenar eminence, at interstimulus intervals (ISIs) of 3 s, progressively increased the perceived intensity of a thermal sensation that followed each contact at an onset latency >2 s. Temporal summation of these delayed (late) sensations was proportional to thermode temperature over a range of 45–53°C, progressing from a nonpainful level (warmth) to painful sensations that could be rated as very strong after 10 contacts. Short-latency pain sensations rarely were evoked by such stimuli and never attained levels substantially above pain threshold for the sequences and temperatures presented. Temporal summation produced by brief contacts was greater in rate and amount than increases in sensory intensity resulting from repetitive ramping to the same temperature by a thermode in constant contact with the skin. Variation of the interval between contacts revealed a dependence of sensory intensity on interstimulus interval that is similar to physiological demonstrations of windup, where increasing frequencies of spike train activity are evoked from spinal neurons by repetitive activation of unmyelinated nociceptors. However, substantial summation at repetition rates of ≥0.33 Hz was observed for temperatures that produced only late sensations of warmth when presented at frequencies <0.16 Hz. Measurements of subepidermal skin temperature from anesthetized monkeys revealed different time courses for storage and dissipation of heat by the skin than for temporal summation and decay of sensory intensity for the human subjects. For example, negligible heat loss occurred during a 6-s interval between two trials of 10 contacts at 0.33 Hz, but ratings of sensory magnitude decreased from very strong levels of pain to sensations of warmth during the same interval. Evidence that temporal summation of sensory intensity during series of brief contacts relies on central integration, rather than a sensitization of peripheral receptors, was obtained using two approaches. In the first, a moderate degree of temporal summation was observed during alternating stimulation of adjacent but nonoverlapping skin sites at 0.33 Hz. Second, temporal summation was significantly attenuated by prior administration of dextromethorphan, a N-methyl-d-aspartate receptor antagonist.
Propagating Neuronal Discharges in Neocortical Slices: Computational and Experimental Study
Authors: Golomb David , Amitai Yael
Published: December 2017

Golomb, David and Yael Amitai. Propagating neuronal discharges in neocortical slices: computational and experimental study. J. Neurophysiol. 78: 1199–1211, 1997. We studied the propagation of paroxysmal discharges in disinhibited neocortical slices by developing and analyzing a model of excitatory regular-spiking neocortical cells with spatially decaying synaptic efficacies and by field potential recording in rat slices. Evoked discharges may propagate both in the model and in the experiment. The model discharge propagates as a traveling pulse with constant velocity and shape. The discharge shape is determined by an interplay between the synaptic driving force and the neuron's intrinsic currents, in particular the slow potassium current. In the model, N-methyl-d-aspartate (NMDA) conductance contributes much less to the discharge velocity than amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) conductance. Blocking NMDA receptors experimentally with 2-amino-5-phosphonovaleric acid (APV) has no significant effect on the discharge velocity. In both model and experiments, propagation occurs for AMPA synaptic coupling g AMPA above a certain threshold, at which the velocity is finite (non-zero). The discharge velocity grows linearly with the g AMPA for g AMPA much above the threshold. In the experiments, blocking AMPA receptors gradually by increasing concentrations of 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) in the perfusing solution results in a gradual reduction of the discharge velocity until propagation stops altogether, thus confirming the model prediction. When discharges are terminated in the model by the slow potassium current, a network with the same parameter set may display discharges with several forms, which have different velocities and numbers of spikes; initial conditions select the exhibited pattern. When the discharge is also terminated by strong synaptic depression, there is only one discharge form for a particular parameter set; the velocity grows continuously with increased synaptic conductances. No indication for more than one discharge velocity was observed experimentally. If the AMPA decay rate increases while the maximal excitatory postsynaptic conductance (EPSC) a cell receives is kept fixed, the velocity increases by ∼20% until it reaches a saturated value. Therefore the discharge velocity is determined mainly by the cells' integration time of input EPSCs. We conclude, on the basis of both the experiments and the model, that the total amount of excitatory conductance a typical cell receives in a control slice exhibiting paroxysmal discharges is only ∼5 times larger than the excitatory conductance needed for raising the potential of a resting cell above its action potential threshold.
Hypoxia-Induced Dysfunction in Developing Rat Neocortex
Authors: Luhmann Heiko J. , Kral Thomas
Published: December 2017

Luhmann, Heiko J. and Thomas Kral. Hypoxia-induced dysfunction in developing rat neocortex. J. Neurophysiol. 78: 1212–1221, 1997. Neocortical slices from young [postnatal day (P) 5–8], juvenile (P14–18), and adult (>P28) rats were exposed to long periods of hypoxia. Field potential (FP) responses to orthodromic synaptic stimulation, the extracellular DC potential, and the extracellular Ca2+concentration ([Ca2+]o] were measured simultaneously in layers II/III of primary somatosensory cortex. Hypoxia caused a 42 and 55% decrease in the FP response in juvenile and adult cortex, respectively. FP responses recorded in slices from young animals were significantly more resistant to oxygen deprivation as compared with the juvenile ( P < 0.01) and adult age group ( P < 0.001) and declined by only 3% in amplitude. In adult cortex, hypoxia elicited, after 7 ± 4.5 min (mean ± SD), a sudden anoxic depolarization (AD) with an amplitude of 14 ± 6 mV and a duration of 0.89 ± 0.28 min at half-maximal amplitude. Although the AD onset latency was significantly longer in P5–8 (12.5 ± 4.9 min, P < 0.001) and P14–18 (8.7 ± 3.2 min, P < 0.002) cortex, the amplitude and duration of the AD was larger in young (45.7 ± 7.6 mV, 2.19 ± 0.71 min, both P < 0.001) and juvenile animals (29.9 ± 9.1 mV, P < 0.001, 0.96 ± 0.26 min, P > 0.05) when compared with the adults. The hypoxia-induced [Ca2+]odecrease was significantly ( P < 0.002) larger in young cortex (1,115 ± 50 μM) as compared with the adult (926 ± 107 μM). Prolongation of hypoxia after AD onset for >5 min elicited in young and juvenile cortex a long-lasting AD with an amplitude of 40.5 mV associated with a decrease in [Ca2+]oby >1 mM. On reoxygenation, only slices from these age groups showed spontaneous repetitive spreading depression in 3 out of 26 cases. In adults, the same protocol caused a significantly ( P < 0.05) smaller and shorter AD and never a spreading depression. However, recovery in synaptic transmission after this long-term hypoxia was better in young and juvenile cortex, indicating a prolonged or even irreversible deficiency in synaptic function in mature animals. Application of ketamine caused a 49% reduction in the initial amplitude of the AD in juvenile cortex but did not significantly affect the AD in slices from adult animals. These data indicate that the young and juvenile cortex tolerates much longer periods of oxygen deprivation as compared with the adult, but that a sufficiently long hypoxia causes severe pathophysiological activity in the immature cortex. This enhanced sensitivity of the immature cortex is at least partially mediated by activation of N-methyl-d-aspartate receptors.
Plasticity of Synaptic Connections in Sensory-Motor Pathways of the Adult Locust Flight System
Authors: Wolf Harald , Büschges Ansgar
Published: December 2017

Wolf, Harald and Ansgar Büschges. Plasticity of synaptic connections in sensory-motor pathways of the adult locust flight system. J. Neurophysiol. 78: 1276–1284, 1997. We investigated possible roles of retrograde signals and competitive interactions in the lesion-induced reorganization of synaptic contacts in the locust CNS. Neuronal plasticity is elicited in the adult flight system by removal of afferents from the tegula, a mechanoreceptor organ at the base of the wing. We severed one hindwing organ and studied the resulting rearrangement of synaptic contacts between flight interneurons and afferent neurons from the remaining three tegulae (2 forewing, 1 hindwing). This was done by electric stimulation of afferents and intracellular recording from interneurons (and occasionally motoneurons). Two to three weeks after unilateral tegula lesion, connections between tegula afferents and flight interneurons were altered in the following way. 1) Axons from the forewing tegula on the operated side had established new synaptic contacts with metathoracic elevator interneurons. In addition, the amplitude of compound excitatory postsynaptic potentials elicited by electric stimulation was increased, indicating that a larger number of afferents connected to any given interneuron. 2) On the side contralateral to the lesion, connectivity between axons from the forewing tegula and elevator interneurons was decreased. 3) The efficacy of the (remaining) hindwing afferents appeared to be increased with regard to both synaptic transmission to interneurons and impact on flight motor pattern. 4) Flight motoneurons, which are normally restricted to the ipsilateral hemiganglion, sprouted across the ganglion midline after unilateral tegula removal and apparently established new synaptic contacts with tegula afferents on that side. The changes on the operated side are interpreted as occupation of synaptic space vacated on the interneurons by the severed hindwing afferents. On the contralateral side, the changes in synaptic contact must be elicited by retrograde signals from bilaterally arborizing flight interneurons, because tegula projections remain strictly ipsilateral. The pattern of changes suggests competitive interactions between forewing and hindwing afferents. The present investigation thus presents evidence that the CNS of the mature locust is capable of extensive synaptic rearrangement in response to injury and indicates for the first time the action of retrograde signals from interneurons.
Are Some Minis Multiquantal?
Authors: Frerking Matthew , Borges Salvador , Wilson Martin
Published: December 2017

Frerking, Matthew, Salvador Borges, and Martin Wilson. Are some minis multiquantal? J. Neurophysiol. 78: 1293–1304, 1997. The amplitude distribution of miniature postsynaptic currents (minis) in many central neurons has a large variance and positive skew, but the sources of this variance and skew are unresolved. Recently it has been proposed that spontaneous Ca2+ influx into a presynaptic bouton with multiple release sites could cause spontaneous multiquantal minis by synchronizing release at all sites in the bouton, accounting for both the large variance and skew of the mini distribution. We tested this hypothesis by evoking minis with internally perfused, buffered Ca2+ and the secretagogue α-latrotoxin, both in the absence of external Ca2+. With these manipulations, the synchronized release model predicts that the mini distribution should collapse to a Gaussian distribution with a reduced coefficient of variation. Contrary to this expectation, we find that mini amplitude distributions under these conditions retain a large variance and positive skew and are indistinguishable from amplitude distributions of depolarization-evoked minis, strongly suggesting that minis are uniquantal.
Neurotensin and Substance P Inhibit Low- and High-Voltage-Activated Ca2+Channels in Cultured Newborn Rat Nucleus Basalis Neurons
Authors: Margeta-Mitrovic Marta , Grigg John J. , Koyano Konomi , Nakajima Yasuko , Nakajima Shigehiro
Published: December 2017

Margeta-Mitrovic, Marta, John J. Grigg, Konomi Koyano, Yasuko Nakajima, and Shigehiro Nakajima. Neurotensin and substance P inhibit low- and high-voltage-activated Ca2+channels in cultured newborn rat nucleus basalis neurons. J. Neurophysiol. 78: 1341–1352, 1997. Inhibition of Ca2+currents by the excitatory neurotransmitters neurotensin and substance P was investigated in cultured nucleus basalis neurons with the use of the whole cell patch-clamp technique. The whole cell Ca2+current, elicited from a holding potential of −80 mV by a step pulse to 0 mV and measured at 100 ms, was inhibited 67.9% by neurotensin and 57.6% by substance P. Low-voltage-activated (LVA) Ca2+current, elicited by a step pulse to −40 mV from a holding potential of −90 mV, was inhibited by both neurotensin (26.2%) and substance P (24.1%). High-voltage-activated Ca2+currents were separated with the use of the Ca2+channel antagonists. Nimodipine (3 μM) inhibited 24.2% of the whole cell Ca2+current elicited by a step to 0 or +10 mV and measured at 100 ms. Under the same conditions, ω-conotoxin (ω-CgTx)-GVIA (0.5 μM) inhibited 46.4%, ω-CgTx-GVIA + nimodipine 58.7%, and ω-CgTx-MVIIC (5 μM) + nimodipine 75.7% of the current. ω-Agatoxin (ω-Aga)-IVA (100 nM) did not produce any effect. Neurotensin inhibition of the whole cell Ca2+current was attenuated by each of these treatments except for the ω-Aga-IVA treatment, which did not change the neurotensin effect. In contrast, neither the ω-Aga-IVA nor the nimodipine treatment had any effect on the substance-P-induced inhibition; the rest of the treatments attenuated the substance-P-induced response. Thus the data indicate that nucleus basalis neurons express LVA as well as L-, N-, and Q-type, but not the P-type, Ca2+currents. N- and Q-type HVA Ca2+currents, as well as LVA Ca2+currents, are inhibited by both neurotensin and substance P. In contrast, L-type current is inhibited by neurotensin but not by substance P. In addition, a fraction of the total whole cell current was resistant to all Ca2+channel antagonists and thus may correspond to the R-type Ca2+current. This residual current was inhibited by both neurotensin and substance P. The inhibition of the whole cell Ca2+current produced by both neurotransmitters was voltage independent, because a large depolarization (+70 mV) was not able to relieve either effect. In cells loaded with 0.1 mM guanosine 5′-[γ-thio]triphosphate, response to both neurotensin and substance P became irreversible, indicating that the effects of both neurotransmitters were mediated through G proteins. However, pertussis toxin did not affect either the neurotensin or the substance P response.
Canal-Specific Excitation and Inhibition of Frog Second-Order Vestibular Neurons
Authors: Straka H. , Biesdorf S. , Dieringer N.
Published: December 2017

Straka, H., S. Biesdorf, and N. Dieringer. Canal-specific excitation and inhibition of frog second-order vestibular neurons. J. Neurophysiol. 78: 1363–1372, 1997. Second-order vestibular neurons (2°VNs) were identified in the in vitro frog brain by their monosynaptic excitation following electrical stimulation of the ipsilateral VIIIth nerve. Ipsilateral disynaptic inhibitory postsynaptic potentials were revealed by bath application of the glycine antagonist strychnine or of the γ-aminobutyric acid-A (GABAA) antagonist bicuculline. Ipsilateral disynaptic excitatory postsynaptic potentials (EPSPs) were analyzed as well. The functional organization of convergent monosynaptic and disynaptic excitatory and inhibitory inputs onto 2°VNs was studied by separate electrical stimulation of individual semicircular canal nerves on the ipsilateral side. Most 2°VNs (88%) received a monosynaptic EPSP exclusively from one of the three semicircular canal nerves; fewer 2°VNs (10%) were monosynaptically excited from two semicircular canal nerves; and even fewer 2°VNs (2%) were monosynaptically excited from each of the three semicircular canal nerves. Disynaptic EPSPs were present in the majority of 2°VNs (68%) and originated from the same (homonymous) semicircular canal nerve that activated a monosynaptic EPSP in a given neuron (22%), from one or both of the other two (heteronymous) canal nerves (18%), or from all three canal nerves (28%). Homonymous activation of disynaptic EPSPs prevailed (74%) among those 2°VNs that exhibited disynaptic EPSPs. Disynaptic inhibitory postsynaptic potentials (IPSPs) were mediated in 90% of the tested 2°VNs by glycine, in 76% by GABA, and in 62% by GABA as well as by glycine. These IPSPs were activated almost exclusively from the same semicircular canal nerve that evoked the monosynaptic EPSP in a given 2°VN. Our results demonstrate a canal-specific, modular organization of vestibular nerve afferent fiber inputs onto 2°VNs that consists of a monosynaptic excitation from one semicircular canal nerve followed by disynaptic excitatory and inhibitory inputs originating from the homonymous canal nerve. Excitatory and inhibitory second-order (2°) vestibular interneurons are envisaged to form side loops that mediate spatially similar but dynamically different signals to 2° vestibular projection neurons. These feedforward side loops are suited to adjust the dynamic response properties of 2° vestibular projection neurons by facilitating or disfacilitating phasic and tonic input components.
Vasopressin/Oxytocin-Related Conopressin Induces Two Separate Pacemaker Currents in an Identified Central Neuron ofLymnaea stagnalis
Authors: van Soest Paul F. , Kits Karel S.
Published: December 2017

van Soest, Paul F. and Karel S. Kits. Vasopressin/oxytocin-related conopressin induces two separate pacemaker currents in an identified central neuron of Lymnaea stagnalis. J. Neurophysiol. 78: 1384–1393, 1997. The molluscan vasopressin/oxytocin analogue Lys-conopressin excites neurons in the anterior lobe of the right cerebral ganglion of the snail Lymnaea stagnalis. Persistent inward currents that underlie the excitatory response were studied with the use of voltage-ramp protocols in the identified neuron RCB1 and other anterior lobe neurons. Under whole cell voltage-clamp conditions, two types of conopressin-activated current could be distinguished on the basis of their voltage dependence: 1) a pacemaker-like current that was activated at potentials above –40 mV (high-voltage-activated current, IHVA) and 2) an inward current that was activated at all potentials between –90 and +10 mV (low-voltage-activated current, ILVA). Ion substitution experiments indicate that sodium is the main charge carrier for IHVAand ILVA. Both currents are differentially affected by cadmium. IHVAand ILVAdiffer in dose dependence, with median effective concentration values of 7.7 × 10−8M and 2.2 × 10−7M, respectively. Vasopressin and oxytocin act as weak agonists for the conopressin responses. The kinetics of desensitization and washout of IHVAand ILVAare different. The HVA response shows little desensitization, whereas the LVA response desensitizes within minutes (time constant80 ± 28 s, mean ± SD). The time constant of washout on removal of conopressin is 159 ± 63 s for IHVAand 36 ± 13 s for ILVA. These results suggest that two distinct conopressin receptors are involved in the activation of both currents. The conopressin-activated currents induce or enhance a region of negative slope resistance in the steady-state current-voltage relation. They differ from a third persistent inward current that is carried by calcium and completely blocked by cadmium. The presumed functional roles of these currents, possibly including autoregulation, are discussed.
Spinal Cord Coordination of Hindlimb Movements in the Turtle: Interlimb Temporal Relationships During Bilateral Scratching and Swimming
Authors: Field Edelle C. , Stein Paul S. G.
Published: December 2017

Field, Edelle C. and Paul S. G. Stein. Spinal cord coordination of hindlimb movements in the turtle: interlimb temporal relationships during bilateral scratching and swimming. J. Neurophysiol. 78: 1404–1413, 1997. Hindlimb interlimb coordination was examined in turtles during symmetrical “same-form” behaviors in which both hindlimbs utilized the same movement strategy (“form”) and during asymmetric “mixed-form” behaviors in which the form exhibited by one hindlimb differed from that of its contralateral partner. In spinal turtles, three forms of scratching were examined: rostral, pocket, and caudal. Bilateral symmetrical same-form scratching was studied for each of the forms. Asymmetric mixed-form scratching (rostral scratching of a hindlimb and pocket scratching of the other hindlimb) was also examined. In intact turtles, two forms of swimming were examined: forward swimming and back-paddling. The symmetrical behavior of bilateral forward same-form swimming and the asymmetric behavior of turning mixed-form swimming (forward swimming of 1 hindlimb and back-paddling of the other hindlimb) were studied. For all behaviors examined, most episodes displayed absolute or 1:1 coordination; in this type of coordination, during each movement cycle that began and ended with the onset of ipsilateral hip flexion, there was a single onset of contralateral hip flexion. For most of these episodes there was out-of-phase coordination between hip movements; the onset of contralateral hip flexion occurred near the onset of ipsilateral hip extension midway through the ipsilateral movement cycle. Bilateral caudal/caudal same-form scratching displayed out-of-phase 1:1 coordination during some episodes and in-phase 1:1 coordination during other episodes. During in-phase coordination, the onset of contralateral hip flexion occurred near the onset of ipsilateral hip flexion close to the start of the ipsilateral movement cycle. In a few cases of bilateral same-form scratching there were episodes of relative or 2:1 coordination; in this type of coordination, during each movement cycle of the slowly moving limb that began and ended with ipsilateral hip flexion, there were two distinct occurrences of the onset of contralateral hip flexion. The observation that out-of-phase movements of the hip occurred during symmetrical as well as asymmetric behaviors is consistent with the hypothesis that timing signals related to hip movement play a major role in interlimb phase control. The neural mechanisms responsible for interlimb phase control are not well understood in vertebrates. The present demonstration of bilateral scratching in spinal turtlessuggests that this preparation may be suitable for additional experiments to examine mechanisms of vertebrate interlimb phasecontrol.
Functional Respiratory Rhythm Generating Networks in Neonatal Mice Lacking NMDAR1 Gene
Authors: Funk G. D. , Johnson S. M. , Smith J. C. , Dong X.-W. , Lai J. , Feldman J. L.
Published: December 2017

Funk, G. D., S. M. Johnson, J. C. Smith, X.-W. Dong, J. Lai, and J. L. Feldman. Functional respiratory rhythm generating networks in neonatal mice lacking NMDAR1 gene. J. Neurophysiol. 78: 1414–1420, 1997. N-methyl-d-aspartate (NMDA) receptor-mediated synaptic transmission is implicated in activity-dependent developmental reorganization in mammalian brain, including sensory systems and spinal motoneuron circuits. During normal development, synaptic interactions important in activity-dependent modification of neuronal circuits may be driven spontaneously ( Shatz 1990b ). The respiratory system exhibits substantial spontaneous activity in utero; this activity may be critical in assuring essential and appropriate breathing movements from birth. We tested the hypothesis that NMDA receptors are necessary for prenatal development of central neural circuits underlying respiratory rhythm generation by comparing the responsiveness of control mice and mutant mice lacking the NMDA receptor R1 subunit (NMDAR1) gene to glutamate receptor agonists and antagonists and comparing endogenous respiratory-related oscillations generated in vitro by brain stem-spinal cord and medullary slice preparations from control and mutant mice. In control mice, local application of NMDA and the non-NMDA receptor agonist, (R,S)-α-amino-3-hydroxy-5-methyl-isoxazole-4-propionic acid hydrobromide (AMPA), over the pre-Bötzinger Complex, the C4 cervical motor neuron pool, and the hypoglossal motor nucleus produced profound increases in inspiratory frequency, tonic discharge on C4 ventral nerve roots, and inward currents in inspiratory hypoglossal motoneurons, respectively. Responses of mutant mice to AMPA were similar. However, mutant mice were completely unresponsive to NMDA applications. Preparations from mutant mice generated a respiratory rhythm virtually identical to control. Results demonstrate that NMDA receptors are not essential for respiratory rhythm generation or drive transmission in the neonate. More importantly, they suggest that NMDA receptors are not obligatory for the prenatal development of circuits producing respiratory rhythm.
Representation of Multiple Kinematic Parameters of the Cat Hindlimb in Spinocerebellar Activity
Authors: Bosco G. , Poppele R. E.
Published: December 2017

Bosco, G. and R. E. Poppele. Representation of multiple kinematic parameters of the cat hindlimb in spinocerebellar activity. J. Neurophysiol. 78: 1421–1432, 1997. Dorsal spinocerebellar tract (DSCT) neurons have been shown to transmit signals related to hindlimb position and movement direction in the anesthetized cat. Because both parameters may be encoded by single neurons, we examined the extent to which their representations might occur sequentially or simultaneously by recording unit activity while the hindlimb was moved passively in the sagittal plane by a robot arm. A center-out/out-center paradigm moved the foot 2 cm from a given position radially to eight positions located 45° apart, holding each position for 8 s. Another paradigm moved the foot along various paths to 20 positions distributed throughout most of the limb's workspace. With each paradigm, we could assess the activity related to foot position and the direction of movement to each position. Modulation of unit activity evoked by center-out/out-center movements was determined for each 1-s postmovement interval by use of a cosine tuning model that specified modulation amplitude and preferred direction. Of 125 units tested, 82.4% were significantly modulated ( P < 0.05) according to this model. We assessed the relative contributions of position and movement by taking advantage of the fact that directional modulation following out-center movements to a common position could only be related to the movement, whereas that following the center-out movements related to both position and movement. The results suggested a simultaneous modulation by these two parameters. Each cell could be characterized by a similar preferred direction for position or movement modulation and the distribution of preferred directions across cells clustered significantly along an axis close to the limb axis. When the limb axis was rotated, the unit preferred directions rotated similarly, on average. Unexpectedly, we found the activity of more than half the cells to be modulated for ≥8 s after out-center movements, implying a persistent movement-related activity well after a movement is completed. These findings were confirmed and extended with the second paradigm by using a multivariate regression model that included terms for position, movement, and their multiplicative interaction. The activity of 81.3% of the 97 neurons tested fit the model ( R 2 > 0.4, P < .0001); 31.6% were modulated exclusively by foot position, and 58.2% simultaneously by both position and movement, with significant interaction. We conclude from our results that DSCT neurons may be modulated simultaneously by limb position and movement, and their preferred directions tend to align with the limb axis. The modulation is interactive such that movement modulation amplitude depends on limb position, and many cells also retain a memory trace of recent movements. The results are discussed in terms of a possible role for the DSCT in encoding limb compliance.
Tyrosine Phosphorylation Modulates Current Amplitude and Kinetics of a Neuronal Voltage-Gated Potassium Channel
Authors: Fadool Debra A. , Holmes Todd C. , Berman Kevin , Dagan Daniel , Levitan Irwin B.
Published: December 2017

Fadool, Debra A., Todd C. Holmes, Kevin Berman, Daniel Dagan, and Irwin B. Levitan. Tyrosine phosphorylation modulates current amplitude and kinetics of a neuronal voltage-gated potassium channel. J. Neurophysiol. 78: 1563–1573, 1997. The modulation of the Kv1.3 potassium channel by tyrosine phosphorylation was studied. Kv1.3 was expressed in human embryonic kidney (HEK 293) cells, and its activity was measured by cell-attached patch recording. The amplitude of the characteristic C-type inactivating Kv1.3 current is reduced by >95%, in all cells tested, when the channel is co-expressed with the constitutively active nonreceptor tyrosine kinase, v-Src. This v-Src–induced suppression of current is accompanied by a robust tyrosine phosphorylation of the channel protein. No suppression of current or tyrosine phosphorylation of Kv1.3 protein is observed when the channel is co-expressed with R385A v-Src, a mutant with severely impaired tyrosine kinase activity. v-Src–induced suppression of Kv1.3 current is relieved by pretreatment of the HEK 293 cells with two structurally different tyrosine kinase inhibitors, herbimycin A and genistein. Furthermore, Kv1.3 channel protein is processed properly and targeted to the plasma membrane in v-Src cotransfected cells, as demonstrated by confocal microscopy using an antibody directed against an extracellular epitope on the channel. Thus v-Src–induced suppression of Kv1.3 current is not mediated through decreased channel protein expression or interference with its targeting to the plasma membrane. v-Src co-expression also slows the C-type inactivation and speeds the deactivation of the residual Kv1.3 current. Mutational analysis demonstrates that each of these modulatory changes, in current amplitude and kinetics, requires the phosphorylation of Kv1.3 at multiple tyrosine residues. Furthermore, a different combination of tyrosine residues is involved in each of the modulatory changes. These results emphasize the complexity of signal integration at the level of a single ion channel.
Repeated Patterns of Distributed Synchrony in Neuronal Assemblies
Authors: Lindsey B. G. , Morris K. F. , Shannon R. , Gerstein G. L.
Published: December 2017

Lindsey, B. G., K. F. Morris, R. Shannon, and G. L. Gerstein. Repeated patterns of distributed synchrony in neuronal assemblies. J. Neurophysiol. 78: 1714–1719, 1997. Models of brain function predict that the recurrence of a process or state will be reflected in repeated patterns of correlated activity. Previous work on medullary raphe assembly dynamics revealed transient changes inimpulse synchrony. This study tested the hypothesis that these variations in synchrony include distributed nonrandom patterns of association. Spike trains were recorded simultaneously in the ventrolateral medulla, n. raphe obscurus, and n. raphe magnus of four anesthetized (Dial), vagotomized, paralyzed, and artificially ventilated adult cats. The “gravitational” representation of spike trains was used to detect moments of impulse synchrony in neuronal assemblies visualized as variations in the aggregation velocities of particles corresponding to each neuron. Template matching algorithms were developed to identify excessively repeating patterns of particle condensation rates. Repeating patterns weredetected in each animal. The reiterated patterns represented anemergent property not apparent in either corresponding firing rate histograms or conventional gravity representations. Overlapping subsets of neurons represented in different patterns were unmasked when the template resolution was changed. The results demonstrate repeated transient network configurations defined by the tightness and duration of synchrony in different combinations of neurons and suggest that multiple information streams are conveyed concurrently by fluctuations in the synchrony of on-going activity.
In Vitro Investigation of Synaptic Relations Between Interneurons Surrounding the Trigeminal Motor Nucleus and Masseteric Motoneurons
Authors: Kolta Arlette
Published: December 2017

Kolta, Arlette. In vitro investigation of synaptic relations between interneurons surrounding the trigeminal motor nucleus and masseteric motoneurons. J. Neurophysiol. 78: 1720–1725, 1997. Because of their many inputs and bilateral projections, interneurons surrounding the trigeminal motor nucleus (MotV) are thought to be very important in control of jaw movements and reflexes. However, their interactions with the trigeminal motoneurons are almost unknown. In the present study an in vitro slice preparation was used to investigate this relationship in rat. The zone bordering MotV has been subdivided into four regions: the supra-, juxta-, and intertrigeminal areas (SupV, JuxtV, and IntV, respectively) and the parvocellular reticular formation ventral and caudal to MotV. Stimulation of all areas evoked short-latency excitatory postsynaptic potentials (EPSPs) in masseteric motoneurons. Frequently the EPSPs masked inhibitory postsynaptic potentials (IPSPs) or were followed by long-lasting inhibitory potentials. Only responses obtained from stimulation of JuxtV and IntV seemed devoid of inhibitory components. The EPSPs were mediated through kainate/α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors, whereas the IPSPs appear to be due to γ-aminobutyric acid and glycine. EPSPs and IPSPs were also recorded in SupV premotor interneurons after stimulation of IntV and MotV, respectively, thus suggesting that reciprocal connections exist between premotor areas and also between premotor interneurons of SupV and inhibitory interneurons located within MotV. It is concluded that the preparation used here will doubtless prove useful for further investigation of the circuitry involved in the bilateral coordination of the jaw.
GABAA-Receptor-Mediated Rebound Burst Firing and Burst Shunting in Thalamus
Authors: Ulrich Daniel , Huguenard John R.
Published: December 2017

Ulrich, Daniel and John R. Huguenard. GABAA-receptor-mediated rebound burst firing and burst shunting in thalamus. J. Neurophysiol. 78: 1748–1751, 1997. The role of γ-aminobutyricacid-A (GABAA)-receptor-mediated inhibitory postsynaptic potentials (IPSPs) in 1) generating rebound burst firing and 2) burst inhibition in thalamocortical (TC) relay cells and inhibitory neurons of nucleus reticularis thalami (nRt) was investigated. Experimental data from previous studies were used to generate artificial synaptic responses in neurons via a computer-driven dynamic clamp. On average, in nRt neurons trains of six or more 10-nS GABAA IPSPs generated rebound bursts of action potentials with a mean delay of 605 ± 32 (SE) ms. In contrast, 10 IPSPs were required for rebound bursts in relay cells, and these occurred with a significantly shorter delay of 327 ± 35 ms. Ca2+-dependent burst responses could be shunted by single IPSPs. Half-maximal burst inhibition was obtained in nRt cells when IPSP conductance was 1.5 times the whole cell input conductance. Burst shunting in TC cells was less effective and required a synaptic- to input-conductance ratio of 3. The relative time window of IPSP burst shunting was broader in nRt (∼20 ms) than TC cells (∼10 ms). We conclude that in nRt cells GABAA-dependent rebound burst responses would occur with a latency that is incompatible with pacemaking of fast (>3-Hz) thalamic rhythm generation such as spindles, yet burst inhibition is powerful. Therefore a likely role for reciprocal intra-nRt connectivity is to mediate lateral inhibition between nRt cells.
Change of Transmitter Release Kinetics During Facilitation Revealed by Prolonged Test Pulses at the Inhibitor of the Crayfish Opener Muscle
Authors: Vyshedskiy Andrey , Lin Jen-Wei
Published: December 2017

Vyshedskiy, Andrey and Jen-Wei Lin. Change of transmitter release kinetics during facilitation revealed by prolonged test pulses at the inhibitor of the crayfish opener muscle. J. Neurophysiol. 78: 1791–1799, 1997. A presynaptic voltage-control method was used to study synaptic facilitation at the inhibitory neuromuscular synapse of the crayfish opener muscle. The expression of the F2 component of facilitation, monitored 150 ms after a conditioning stimulus, was examined by systematically changing the duration of the presynaptic test pulse. (Test pulses in all experiments were depolarized to 0 mV.) Control and facilitated inhibitory postsynaptic potentials (IPSPs) exhibited identical time courses when test pulse duration was brief (∼2 ms). When the duration of the test pulse was increased beyond 2 ms, the transmitter release time course shifted to an earlier point in time during facilitation. Meanwhile, the increase in total transmitter release, measured from inhibitory postsynaptic conductance (IPSG) area (total release), became less pronounced with increasing duration of the test pulse. With a 20-ms test pulse, facilitation did not cause any detectable change in total release but the half-maximal point of the facilitated IPSG shifted by 3 ms (release shift). This change in release kinetics was not associated with a decrease in minimal synaptic delay. Furthermore, the relationship between total release and presynaptic pulse duration suggested that the transmitter release activated by a 20-ms pulse can be defined as a distinct component of continuous transmitter release (early component). The facilitation process accelerated the release kinetics of the early component but did not modify its total transmitter content. To test the hypothesis that the release shift is indeed mediated by the same mechanism that increases IPSP amplitude during facilitation, we investigated the correlation between the release shift and IPSP amplitude change. The two parameters were significantly correlated when the magnitude of facilitation was changed 1) during the decay of facilitation and 2) by varying the strength of the conditioning stimulus. The experimental approach reported here provides two new physiological parameters, release shift and total release, for the analysis of synaptic facilitation.
Receptive Properties of Mouse Sensory Neurons Innervating Hairy Skin
Authors: Koltzenburg Martin , Stucky Cheryl L. , Lewin Gary R.
Published: December 2017

Koltzenburg, Martin, Cheryl L. Stucky, and Gary R. Lewin. Receptive properties of mouse sensory neurons innervating hairy skin. J. Neurophysiol. 78: 1841–1850, 1997. Using an in vitro nerve skin preparation and controlled mechanical or thermal stimuli, we analyzed the receptive properties of 277 mechanosensitive single primary afferents with myelinated ( n = 251) or unmyelinated ( n = 26) axons innervating the hairy skin in adult or 2-wk-old mice. Afferents were recorded from small filaments of either sural or saphenous nerves in an outbred mice strain or in the inbred Balb/c strain. On the basis of their receptive properties and conduction velocity, several receptor types could be distinguished. In adult animals (>6 wk old), 54% of the large myelinated fibers (Aβ, n = 83) showed rapidly adapting (RA) discharges to constant force stimuli and probably innervated hair follicles, whereas 46% displayed a slowly adapting (SA) response and probably innervated Merkel cells in touch domes. Among thin myelinated fibers (Aδ, n = 91), 34% were sensitive D hair receptors and 66% were high-threshold mechanoreceptors (AM fibers). Unmyelinated fibers had high mechanical thresholds and nociceptive functions. All receptor types had characteristic stimulus-response functions to suprathreshold force stimuli. Noxious heat stimuli (15-s ramp from 32 to 47°C measured at the corium side of the skin) excited 26% (5 of 19) of AM fibers with a threshold of 42.5 ± 1.4°C (mean ± SE) and an average discharge of 15.8 ± 9.7 action potentials and 41% (7 of 17) C fibers with a mean threshold of 37.6 ± 1.9°C and an average discharge of 22.0 ± 6.0 action potentials. Noxious cold stimuli activated 1 of 10 AM fibers and 3 of 10 C fibers. One of 10 C units responded to both heat and cold stimuli. All types of afferent fibers present in adult mice could readily be recognized in mice at postnatal day 14. However, fibers had reduced conduction velocities and the stimulus-response function to mechanical stimuli was more shallow in all fibers except for the D hairs. In juvenile mice, 22% of RA units also displayed an SA response at high stimulus intensities; these units were termed RA/SA units. We conclude that all types of cutaneous afferent fibers are already committed to their phenotype 2 wk after birth but undergo some maturation over the following weeks. This preparation has great potential for the study of transgenic mice with targeted mutations of genes that code factors that are involved in the specification of sensory neuron phenotypes.