bluuebunny/crossref_metadata_2025 huggingface dataset:
Site of action potential initiation in amphibian retinal ganglion cells
Authors: Carras P. L. , Coleman P. A. , Miller R. F.
Published: December 2017

1. We applied morphological, pharmacological, electrophysiological, and computer simulation techniques to analyze the origin of impulse initiation in amphibian retinal ganglion cells. 2. Morphological studies of retinal ganglion cells in the mudpuppy (Necturus maculosus) and larval tiger salamander (Ambystoma tigrinum) were carried out with the use of either retrograde or intracellular labeling with horseradish peroxidase. These studies identified a characteristic thinning of the axon that begins after the initial segment of axon emerges from the ganglion cell soma or primary dendrite. Morphometric analysis of the thin segment revealed an average length of 74 microns with a standard deviation of 22 microns. For 20 conventionally placed ganglion cells, the length of the thin segment could not be correlated with soma size, initial segment diameter, or distance from the optic disk. There was also little or no correlation for seven displaced ganglion cells. The diameter of the thin segment was below reliable estimation by light microscopy. 3. We studied the possible significance of the thin axonal segment for ganglion cell impulse generation through a combination of electrophysiological recordings (intracellular and whole-cell recordings) together with computer modeling experiments. 4. Electrophysiological experiments are consistent with the idea that the thin segment and cell soma are less excitable than the initial segment region, which appears to be the principal site of initiation of the nerve impulse. The initial segment is that portion of the axon that is bounded by the soma (or proximal dendrite) at its origin and the thin segment at its distal end. 5. Computer simulations of impulse activation were carried out with the use of two different anatomic constraints: one class of simulations did not take into account the thin segment and assumed uniform cylinder conditions, whereas the other class of simulations included a model of the thin axonal segment. These comparative simulations indicate that the thin segment must contain a relatively high density of voltage-gated Na+ channels and support impulse traffic to account for physiological observations on orthodromic and antidromic impulse propagation. In addition, to match the physiological recordings, it is necessary for both the initial segment and the soma compartments to contain moderately high levels of Na+ channels. 6. Our physiological and simulation studies are consistent with the idea that the nerve impulse is normally initiated in the initial segment of axon and then spreads to activate a somatic impulse in the retrograde direction and the axonal impulse in the anterograde direction.(ABSTRACT TRUNCATED AT 400 WORDS)
Synaptic connections between nonspiking afferent neurons and motor neurons underlying phase-dependent reflexes in crayfish
Authors: Skorupski P.
Published: December 2017

1. This paper analyzes the synaptic connections made by nonspiking afferent neurons of the thoracocoxal muscle receptor organ (TCMRO) with basal limb motor neurons in the crayfish. The T fiber, a dynamically sensitive afferent, monosynaptically excites promotor motor neurons. Evidence suggests that both tonic graded chemical transmission and electrical synaptic transmission may be involved, depending on the motor neuron under consideration. 2. In preparations in the active state (spontaneously producing reciprocal motor patterns), the T fiber also inhibits promotor motor neurons in a phase-dependent manner. This inhibitory pathway is probably indirect, because it involves additional synaptic delay. 3. The statically sensitive S fiber also excites promotor motor neurons, but phase-dependent inhibition of promotor motor neurons by the S fiber was not seen. 4. The T fiber excites a subclass of remotor motor neurons (group 1) by a combination of direct chemical input and electrical input. This connection underlies the positive feedback reflex that excites these remotor motor neurons, in a phase-dependent manner, on stretch of the TCMRO during the active state. In inactive preparations, this connection remains subthreshold. 5. Central synaptic outputs of group 1 remotor motor neurons can also inhibit promotor motor neurons. This pathway may contribute to the phase-dependent reflex inhibition of promotor motor neurons that occurs in the active state.
Burst generation in neocortical neurons after GABA withdrawal in the rat
Authors: Silva-Barrat C. , Araneda S. , Menini C. , Champagnat J. , Naquet R.
Published: December 2017

1. gamma-Aminobutyric acid (GABA) withdrawal syndrome (GWS) represents a particular model of focal epilepsy consecutive to the interruption of a chronic intracortical GABA infusion and is characterized by the appearance of focal epileptic electroencephalographic (EEG) discharges and localized clinical signs on withdrawal of GABA. Effects of Ca2+ channel blockers and N-methyl-D-aspartate (NMDA) antagonists were evaluated in living rats presenting a GWS after interruption of a 5-day GABA infusion into the somatomotor cortex and in neocortical slices obtained from such rats. Bursting properties and morphology of neurons were also analyzed in slices. 2. In living rats, the noncompetitive NMDA antagonist phencyclidine [1-(1-phenylcyclohexyl)piperidine] and the Ca2+ antagonist flunarizine [E-1 (bis(4fluorophenyl)methyl)-4(3phenyl2-propenyl)-piperazine] were administered systemically to two groups of rats. Rats in the first group (n = 12) were injected with the drug 30-60 min before discontinuation of the GABA infusion. In this case, phencyclidine (10 mg/kg ip) prevented the development of GWS (n = 5), whereas flunarizine (40 mg/kg ip) had no consistent effect on the GWS appearance and characteristics (n = 7). Rats in the second group (n = 12) were injected 60-90 min after GABA discontinuation, i.e., during a fully developed GWS. In that case, neither drug suppressed GWS. 3. Neuronal activities in the epileptic focus were studied in slices with conventional intracellular recording and stimulation techniques. From the 65 neurons recorded, 29 responded with EPSPs and paroxysmal depolarization shifts (PDSs) to white matter stimulation (synaptic bursting or SB cells). Nineteen other neurons presented, in addition to synaptically induced PDSs, bursts of action potentials (APs) induced by intracellular depolarizing current injection (intrinsic bursting or IB cells). The remaining 17 neurons presented no bursting properties to either synaptic stimulation or depolarizing current injection (nonbursting or NB cells). 4. The recorded neurons were located 0.7-1.2 mm distant from the lesion because of the penetration of the GABA infusion cannula. Intracellular injection of neurons (n = 4) with biocytin or Lucifer yellow revealed that both SB and IB neurons were large, spiny pyramidal neurons localized in layer V of the sensorimotor cortex. 5. Bath application of the selective antagonist of NMDA receptors DL-2amino-5phosphonovalerate or DL-2amino-7phosphonoheptanoate (10-50 microM) reversibly reduced the amplitude (by 25-50%) and the duration (by 20-25%) of PDSs in all cases (n = 17).(ABSTRACT TRUNCATED AT 400 WORDS)
Excitatory postsynaptic potentials recorded from regular-spiking cells in layers II/III of rat sensorimotor cortex
Authors: Hwa G. G. , Avoli M.
Published: December 2017

1. Intracellular recording techniques were used to investigate the physiological and pharmacological properties of stimulus-induced excitatory postsynaptic potentials (EPSPs) recorded in regular-spiking cells located in layers II/III of rat sensorimotor cortical slices maintained in vitro. 2. Depending on the strength of the extracellular stimuli, a pure EPSP or an EPSP-inhibitory postsynaptic potential sequence was observed under perfusion with normal medium. The EPSPs displayed short latency of onset [2.4 +/- 0.7 (SD) ms] and were able to follow repetitive stimulation (tested less than or equal to 5 Hz). Variation of the membrane potential (Vm) revealed two types of voltage behavior for the short-latency EPSP. The first type decreased in amplitude with depolarization and increased in amplitude with hyperpolarization. In contrast, the second type behaved anomalously by increasing and decreasing in size after depolarization and hyperpolarization, respectively. 3. Several experimental procedures were carried out to investigate the mechanism underlying the anomalous voltage behavior of the EPSP. Results indicated that this type of Vm dependency could be mimicked by an intrinsic response evoked by a brief pulse of depolarizing current and could be abolished by N-(2,6-dimethylphenylcarbamoylmethyl)triethylammonium bromide (50 mM). Furthermore, the EPSP was not sensitive to the N-methyl-D-aspartate (NMDA) receptor antagonist 3-((+-)-2-carboxypiperazin-4-yl)-propyl-1-phosphonate (CPP, 10 microM). Thus the anomalous voltage relationship of the neuronal membrane. 4. The involvement of non-NMDA receptors in excitatory synaptic transmission was investigated with their selective antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 1-10 microM). This drug greatly reduced or completely blocked the EPSP in a dose-dependent manner (1-10 microM). The IC50 for the CNQX effect was approximately 2 microM. In the presence of CNQX (10 microM) and glycine (10 microM), synaptic stimulation failed to elicit firing of action potential. However, a CPP-sensitive EPSP was observed. 5. When synaptic inhibition was reduced by low concentration of bicuculline methiodide (BMI, 1-2 microM), extracellular stimulation revealed late EPSPs (latency to onset: 10-30 ms) that were not discernible in normal medium. Similar to the short-latency EPSP, the Vm dependency displayed by this late EPSP could be modified by inward membrane rectifications. The late EPSP appeared to be polysynaptic in origin because 1) its latency of onset was long and variable and 2) it failed to follow repetitive stimuli delivered at a frequency that did not depress the short-latency EPSP.(ABSTRACT TRUNCATED AT 400 WORDS)
Physiological and morphological correlations of horizontal cells in the mudpuppy retina
Authors: Kim H. G. , Miller R. F.
Published: December 2017

1. Horizontal cells (HCs) of the mudpuppy (Necturus maculosus) retina were physiologically characterized with the use of intracellular recordings in a superfused, dark-adapted, retina-eyecup preparation. 2. Physiological analysis included an evaluation of rod versus cone input and a determination of the receptive field size with the use of a displaced slit of light. 3. The morphology of HCs was established through intracellular staining with horseradish peroxidase (HRP) and Lucifer yellow mixed in a single electrode. 4. Three types of horizontal cells were identified, each associated with a distinct morphology. Physiological subtypes included luminosity (L) and chromaticity (C) cells. Morphological diversities included single axon-bearing, multiple axon-bearing and, nonaxon-bearing cells. All C-type HCs lacked axons. 5. Approximately 90% of HCs encountered in this study were L-type cells, which received sign-conserving inputs from both rods and cones. These cell types contained one or more long axons that often stretched greater than 500 microns. This group was morphologically diverse, particularly with respect to variations in the number of axons, but we were unable to correlate this diversity with any unique set of physiological properties. 6. Several C-type HCs were identified (n = 8). These cells depolarized to a low-intensity, short-wavelength (SW) stimulus, whereas they hyperpolarized to high-intensity, long-wavelength stimuli. Morphologically, these cells were axonless (n = 4), with relatively small dendritic fields. 7. A third group of HCs were classified as "short wavelength preferring" HCs (n = 7). These cells responded better to a SW stimulus at all intensity levels. They were thus dissimilar to the common L-type HCs, which showed an apparent rod to cone transition as the stimulus intensity increased, suggestive of a shift from rod to cone preference. Morphologically, these cells were axonless (n = 2), but had broader dendritic fields than the C-type HCs. 8. Our observations indicate that the horizontal cell population of the mudpuppy retina is considerably more complex than previously supposed. The existence of both axon-bearing and axonless HCs, which could be correlated with L- and C-type physiology, implies that HCs may support more than one function in outer retina processing.
Characteristics of near response cells projecting to the oculomotor nucleus
Authors: Zhang Y. , Mays L. E. , Gamlin P. D.
Published: December 2017

1. Previous work has shown neurons just dorsal and lateral to the oculomotor nucleus that increase their firing rate with increases in the angle of ocular convergence. It has been suggested that the output of these midbrain near response cells might provide the vergence command needed by the medial rectus motoneurons. However, lens accommodation ordinarily accompanies convergence, and a subsequent study showed that only about one-half of these midbrain near response cells carried a signal related exclusively to vergence. One hypothesis suggested by this finding is that this subgroup of neurons might have a unique role in providing a "pure" vergence signal to the medial rectus motoneurons. 2. In the present study extracellular recordings were made from midbrain near response cells in monkeys while eye position and lens accommodation were measured. The monkeys viewed targets through an optical system that allowed the accommodative and ocular vergence demands to be manipulated independently. This approach was used to produce a partial dissociation of accommodative and vergence responses, so that an accommodative and vergence coefficient could be determined for each cell, by the use of the following equation FR = R0 + kda x AR + kdv x CR where FR is the firing rate of the near response cell, R0 is the predicted firing rate for a distant target, kda is the (dissociated) accommodation coefficient, AR is the accommodative response, kdv is the (dissociated) vergence coefficient, and CR is the convergence response. 3. The vergence and accommodation coefficients were determined for a large number of midbrain near response cells, including a subset that could be antidromically activated from the medial rectus subdivisions of the oculomotor nucleus. Some near response neurons were found with signals related exclusively to convergence (i.e., kdv greater than 0 and kda = 0), whereas several others had signals related exclusively to lens accommodation (i.e., kda greater than 0 and kdv = 0). The majority of the near response cells had signals related to both responses (i.e., kda not equal to 0 and kdv not equal to 0). Furthermore, the vergence and accommodation coefficients of near response cells appeared to be continuously distributed. Some cells had negative accommodation or vergence coefficients. 4. The 17 near response cells that could be antidromically activated from the oculomotor nucleus presumably provide vergence signals to the medial rectus motoneurons. Although all had positive vergence coefficients, only four of these cells carried signals that were related exclusively to vergence.(ABSTRACT TRUNCATED AT 400 WORDS)
Velocity of shortening of single motor units from rat soleus
Authors: Devasahayam S. R. , Sandercock T. G.
Published: December 2017

1. The force-velocity relationship of a motor unit can provide insight into the contractile proteins of its constituent fibers as well as fundamental information about the function and use of the motor unit. Although the force-velocity profiles of whole muscle and skinned mammalian fibers have been studied, technical difficulties have prevented similar studies on motor units. A technique is presented to directly measure the velocity of shortening of individual motor units from in vivo rat soleus muscle. 2. The soleus muscles of anesthetized rats were dissected free of surrounding tissue while their nerve and blood supplies were preserved. Both tendons were cut, and the distal tendon was attached to a servomechanism to control muscle length, whereas the proximal tendon was attached to a force transducer. Single motor units were stimulated via the ventral roots. 3. The major problem encountered in measuring the force-velocity profile of a motor unit was that the force from the large number of passive fibers and connective tissue in the soleus confounded the force produced by the small number of active fibers in the motor unit. This problem was minimized by measuring active motor unit tension during an isovelocity ramp. This allowed experimental measurement of the passive tension by shortening the muscle with an identical isovelocity ramp without, however, stimulating the motor unit. Active tension was estimated by subtracting the passive tension waveform from the waveform recorded when the motor unit was active. 4. The method substantially reduced the noise from the passive fibers; however, problems remained. The probable sources of error are discussed, with the most significant being the elasticity associated with the blood and nerve connections to surrounding tissue. The elasticity prevents uniform shortening velocities along the length of the active fibers, thereby introducing a systematic bias to measurements made at high velocities. These errors are most pronounced when the data are extrapolated to determine the maximum velocity of shortening (Vmax). Determination of velocity at peak power (Vpp) is a more robust measure; however, of the 34 motor units studied, only 19 exhibited a distinct peak in the power-force curve, indicating residual noise. 5. To assess the validity of using twitch contraction time as an index of the velocity of shortening, when possible, Vmax and Vpp of each motor unit were correlated with the inverse of its twitch contraction time. The correlation was poor (r less than 0.2), indicating that, although widely used, twitch contraction time is a poor index of contractile speed.
Motor-unit categorization based on contractile and histochemical properties: a glycogen depletion analysis of normal and reinnervated rat tibialis anterior muscle
Authors: Totosy de Zepetnek J. E. , Zung H. V. , Erdebil S. , Gordon T.
Published: December 2017

1. Isolated and glycogen-depleted motor units (MUs) have been studied in normal and reinnervated tibialis anterior (TA) muscles of the rat to examine 1) the correspondence between physiological and histochemical classifications, 2) the extent to which unit properties cluster according to type, 3) the relation between unit force and fatigability, and 4) the extent to which reinnervated MUs recover their former properties. 2. MUs were isolated by ventral root dissection and stimulation in reinnervated and normal TA muscles, 3.5-8 mo after common peroneal (CP) nerve section and resuture and in age-matched control rats, respectively. The units were characterized physiologically for classification into four types: slow twitch (S), fast twitch, fatigue resistant (FR), fast twitch fatigue intermediate (FI), and fast twitch fatigue sensitive (FF). Four muscle fiber types were identified histochemically with the use of a modification of the techniques of Brooke and Kaiser, and Guth and Samaha to delineate fiber subtypes on the basis of the pH sensitivity of myofibrillar adenosine triphosphatase (ATPase). 3. Neither the time-to-peak twitch force development nor the profile of unfused tetanus ("sag test") was unambiguous in separating fast from slow MUs. However, all units with a time to peak greater than 22 ms were fatigue resistant, and this time was chosen to delineate fast from slow. The fast unit population was further subdivided on the basis of their fatigability. There is normally a small proportion of S units (6% S) that increased to 20% after reinnervation. Although the fast population was subdivided, there was a continuous distribution of fatigue indexes in normal and reinnervated muscles with the highest number of fast units falling into the FI category. The proportions of fast units were 28% FR, 45% FI, and 21% FF in normal muscles and 29% FR, 38% FI, and 13% FF in reinnervated muscles. 4. In normal muscles, delineation of fast and slow fibers and subdivision of fast fiber types on the basis of acid and alkali stability of myofibrillar ATPase provided a histochemical classification that showed 78% correspondence with physiological classification of the same identified units. In reinnervated muscles the correspondence between physiological and histochemical classifications was reduced to 72%. 5. The normal correlation between MU fatigability and isometric force in TA muscles was not seen in reinnervated muscles that contained more FR MUs. Mean fatigue index from normal units was significantly less at 0.55 +/- 0.03 (mean +/- SE) compared with 0.68 +/- 0.03 from reinnervated units.(ABSTRACT TRUNCATED AT 400 WORDS)
Ammonium ions abolish excitatory synaptic transmission between cerebellar neurons in primary dissociated tissue culture
Authors: Raabe W.
Published: December 2017

1. Transmitter glutamate is thought to be derived from glutamine via cleavage by glutaminase. NH+4 inhibits glutaminase. Therefore the decrease of glutamatergic excitatory synaptic transmission by NH+4 was thought to be due to the inability of glutamine to serve as precursor for glutamate. However, in cat spinal cord, NH+4 abolished excitatory synaptic transmission by a conduction block for action potentials in presynaptic terminals. The conduction block prevented inferences as to the effects of NH+4 on the availability of glutamate for synaptic transmission. This study reexamines the effects of NH+4 on glutamatergic excitatory synaptic transmission in cerebellar neurons in tissue culture. 2. Whole-cell patch voltage-clamp recordings were obtained from presumed Purkinje cells. Extracellular stimulation of presumed granule cells produced mono- and polysynaptic excitatory postsynaptic currents (EPSCs). In addition, presumed Purkinje cells showed spontaneous EPSCs that occurred independently of the addition of tetrodotoxin (TTX) or Cd2+ to the extracellular solution. 3. NH+4 (5–10 mM) abolished evoked mono- and polysynaptic EPSCs without abolishing spontaneous EPSCs and without significant effects on action currents in the Purkinje cell soma. 4. Increase of K+ in the extracellular solution to 10-12 from 5 mM abolished evoked EPSCs without abolishing spontaneous EPSCs and without significant effects on action currents in the Purkinje cell soma. 5. Mixtures of NH+4 and K+, with each ion in a concentration insufficient to affect evoked EPSCs when given alone, abolished evoked EPSCs when the sum of NH+4 and K+ exceeded 10–12 mM. 6. Increase of intracellular pH by trimethylamine had no effect on evoked and spontaneous EPSCs.(ABSTRACT TRUNCATED AT 250 WORDS)
Some properties of receptive fields of olfactory mitral/tufted cells in the frog
Authors: Jiang T. , Holley A.
Published: December 2017

1. Different regions of the frog's olfactory epithelium were stimulated with nine glass micropipettes either individually or simultaneously in different combinations. The stimulus was a positive electrical pulse (4 s) consisting of a progressive increase, a plateau, and a progressive decrease in current intensity. Extra- and intracellular recordings were made from olfactory bulb mitral/tufted cells. Some of these cells were identified by intracellular injection of Lucifer yellow. 2. The action potential response patterns of mitral/tufted cells during the different phases of the stimulation were coded according to whether the activity was increased or decreased compared with its spontaneous level just before stimulation. Neural responses were classified into 11 types: individual neurons responded with different response types to stimuli delivered at different epithelial sites. On the basis of these response types, it was found that neurons could be classified into two groups. All response types in one group included an initial phase of increased discharge (excitation), whereas all types in the other group included an initial phase of decreased activity (suppression). Neurons that displayed response types belonging to one group never displayed those of the other group. It was thus concluded that a given neuron responded either always with an increased activity or always with a decreased activity, whatever the location of the stimulus. 3. The receptive field of a mitral/tufted cell appeared to be homogenous and not divided into areas of different properties, at least under the present experimental conditions. The extent of a receptive field was estimated by determining the number of effective epithelial sites (where an electrical stimulus evoked a response from a bulbar neuron).(ABSTRACT TRUNCATED AT 400 WORDS)
ATP-gated current in dissociated rat nucleus solitarii neurons
Authors: Ueno S. , Harata N. , Inoue K. , Akaike N.
Published: December 2017

1. The excitatory response of extracellularly applied ATP was investigated in freshly dissociated rat nucleus tractus solitarii neurons under whole-cell configuration using the ”concentration-clamp” technique. 2. At a holding potential of -70 mV, 100 microM ATP evoked inward current that was slowly desensitized in the continuous presence of ATP. The ATP-gated current increased in a concentration-dependent manner over the concentration range between 10 microM and 1 mM. The half-maximum concentration was 31 microM and the Hill coefficient was 1.2. 3. The potency of ATP analogues for the purinergic receptor was in the order of ATP = 2-methylthio-ATP much greater than ADP greater than alpha,beta-methylene ATP. Neither adenosine nor AMP evoked any responses. The order was consistent with a P2y receptor subtype. 4. The current-voltage relationship for the 100 microM ATP response showed a clear inward rectification at positive potentials beyond -50 mV. The reversal potential of the ATP-gated current was +13 mV. 5. The time constants of activation and inactivation of the ATP-gated current solution were dependent on the extracellular ATP concentration, and both kinetics became faster at higher ATP concentrations. 6. The ATP-gated current was also elicited in an external solution containing Ca2+ as a permeable cation. The inactivation kinetics in an external solution containing 75 mM Ca2+ were faster than those in an external solution with 150 mM Na+. 7. Calculated relative permeability ratios were PNa/PCs = 1.64 ([Na+]o = 30-150 mM), PCa/PCs = 2.17 ([Ca2+]o = 2 mM). Anions were not measurably permeable in this preparation.
Depression of postsynaptic potentials by high-frequency stimulation in embryonic motoneurons grown in spinal cord slice cultures
Authors: Streit J. , Luscher C. , Luscher H. R.
Published: December 2017

1. In embryonic cocultures of spinal cord, dorsal root ganglia, and muscle, excitatory postsynaptic potentials (EPSPs) were recorded in motoneurons during focal electrical stimulation of the dorsal root ganglia or the spinal cord. 2. EPSPs were depressed in amplitude at high-frequency stimulation relative to a control frequency of 0.5 Hz by 47 and 75% at 5 and 10 Hz, respectively. This was true for composite EPSPs and unitary EPSPs. 3. The depression showed a wide range of variability between individual experiments. The degree of depression at 5 Hz was negatively correlated to the rate of spontaneous excitatory input the motoneurons received. There was no correlation to the soma size, the average amplitude of the EPSPs, the rheobase, or the input resistance of the motoneurons. 4. An increase in latency of EPSPs was observed concomitant with or preceding the synaptic depression in most experiments. Total transmission failures, which were absent at low-frequency stimulation, appeared during depression. 5. Large incremental steps in amplitude could be seen during depression, suggesting that several release sites were switched off and on together. 6. Decreasing the extracellular calcium concentration from 5 to 1 mM led to a decrease in the frequency sensitivity of the synaptic efficacy and to a decrease of the EPSP amplitude and latency. 7. Measurements of the antidromic conduction of action potentials evoked in the axons and recorded in the somata of dorsal root ganglion cells revealed an increase in latency and the appearance of conduction failures at stimulation frequencies of 1-10 Hz. The frequency modulation of conduction was decreased in 1 mM compared with 5 mM external calcium. 8. Together these findings suggest that conduction failures in the presynaptic axons contribute to the synaptic depression of EPSPs in embryonic motoneurons.
Excitotoxic acid lesions of the primate subthalamic nucleus result in reduced pallidal neuronal activity during active holding
Authors: Hamada I. , DeLong M. R.
Published: December 2017

1. To gain a better understanding of the pathophysiology of hemiballismus in primates, and to test directly the hypothesis that the subthalamopallidal projection is excitatory, we studied the effects of lesions of the subthalamic nucleus (STN) on neuronal activity in the globus pallidus (GP) of monkeys during performance of a motor behavioral task. 2. Animals were trained to position and hold a manipulandum to which torque pulses were applied, producing elbow flexion and extension. The activity of neurons in the external (GPe) and internal (GPi) segments of GP was recorded in two monkeys during task performance before and after STN lesions. The STN was lesioned by the fiber-sparing neurotoxins ibotenic acid and/or kainic acid. 3. After lesioning, the firing rate of neurons in both segments of GP, which was measured during the period of holding before torque application, was significantly decreased in both animals. The mean of discharge rates of GPi neurons decreased (P < 0.001) from 69.8 (n = 169, SD = 21.6) to 47.4 spikes/s (n = 180, SD = 22.6) after lesioning. The mean of discharge rates of GPe neurons decreased from 63.6 spikes/s (n = 218, SD = 25.1) before lesions to 41.0 spikes/s (n = 208, SD = 18.1) after lesioning. 4. These results provide further evidence that STN gives rise to a major excitatory input to both segments of the GP and support the hypothesis that dyskinesias result from decreased GPi output.
A computer-based model for realistic simulations of neural networks. II. The segmental network generating locomotor rhythmicity in the lamprey
Authors: Wallen P. , Ekeberg O. , Lansner A. , Brodin L. , Traven H. , Grillner S.
Published: December 2017

1. To analyze the function of the spinal interneuronal network generating locomotion in the lamprey CNS, a vertebrate model system, we performed computer simulations with realistic model neurons possessing the essential properties of their biological counterparts. 2. The segmental network has been simulated by modeling experimentally established types of neurons with their specific membrane properties and synaptic interconnections. Fictive locomotor activity, which can be experimentally induced by elevating the background excitability by bath application of excitatory amino acids, was simulated by opening membrane conductances for kainate/alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) or N-methyl-D-aspartate (NMDA) receptors. Kainate/AMPA receptor activation induced a rhythm in the middle and upper part of the physiological burst frequency range, whereas NMDA receptor activation evoked bursting in the lower part of the range, which corresponds well to earlier experimental findings. 3. Several factors contributing to the termination of the burst were studied and their interaction was assessed in simulations of the network. 1) The summation of spike afterhyperpolarizations (late AHPs), leading to adaptation of the discharge, acts as a primary burst-terminating factor at lower rates of kainate/AMPA-induced bursting, and it also interacts with the NMDA-induced oscillatory membrane properties during slow rhythmicity. 2) The termination of the depolarized NMDA plateau is another important factor during NMDA-evoked rhythmicity. 3) The synaptic inhibition from lateral interneurons to the interneurons mediating reciprocal inhibition is important at higher rates of kainate/AMPA-induced bursting. 4. The mechanism of action of 5-hydroxytryptamine (5-HT) on the lamprey segmental network was further investigated by simulation. 5-HT is known to lower the burst frequency during fictive locomotion and also to decrease the conductance through the Ca(2+)-dependent K+ channels, and thereby the size of the late AHP that follows the action potential. Decreasing this conductance in the network simulations resulted in a lesser amount of AHP summation and thereby less frequency adaptation during the burst, longer bursts, and a lower locomotor frequency. Thus the selective action of 5-HT on the Ca(2+)-dependent K+ channels, and hence on the AHP, can account for the modulatory effect on the fictive locomotor rhythm seen experimentally. 5. The results demonstrate that the present simulation of the segmental network can account for essential features of the motor pattern seen experimentally during lamprey locomotion.(ABSTRACT TRUNCATED AT 400 WORDS)
Neural circuit tuning fly visual interneurons to motion of small objects. I. Dissection of the circuit by pharmacological and photoinactivation techniques
Authors: Warzecha A. K. , Egelhaaf M. , Borst A.
Published: December 2017

1. Visual interneurons tuned to the motion of small objects are found in many animal species and are assumed to be the neuronal basis of figure-ground discrimination by relative motion. A well-examined example is the FD1-cell in the third visual neuropil of blowflies. This cell type responds best to motion of small objects. Motion of extended patterns elicits only small responses. As a neuronal mechanism that leads to such a response characteristic, it was proposed that the FD1-cell is inhibited by the two presumably GABAergic and, thus, inhibitory CH-cells, the VCH- and the DCH-cell. The CH-cells respond best to exactly that type of motion by which the activity of the FD1-cell is reduced. The hypothesis that the CH-cells inhibit the FD1-cell and, thus, mediate its selectivity to small moving objects was tested by ablating the CH-cells either pharmacologically or by photoinactivation. 2. After application of the gamma-aminobutyric acid (GABA) antagonist picrotoxinin, the FD1-cell responds more strongly to large-field than to small-field motion, i.e., it has lost its small-field selectivity. This suggests that the tuning of the FD1-cell to small moving objects relies on a GABAergic mechanism and, thus, most likely on the CH-cells. 3. The role of each CH-cell for small-field tuning was determined by inactivating them individually. They were injected with a fluorescent dye and then ablated by laser illumination. Only photoinactivation of the VCH-cell eliminated the specific selectivity of the FD1-cell for small-field motion. Ablation of the DCH-cell did not significantly change the response characteristic of the FD1-cell. This reveals the important role of the VCH-cells in mediating the characteristic sensitivity of the FD1-cell to motion of small objects. 4. The FD1-cell is most sensitive to motion of small objects in the ventral part of the ipsilateral visual field, whereas motion in the dorsal part influences the cell only weakly. This specific feature fits well to the sensitivity of the VCH-cell to ipsilateral motion that is most pronounced in the ventral part of the visual field. The spatial sensitivity distribution of the FD1-cell matches also the characteristics of figure-ground discrimination and fixation behavior.
Receptive properties of myelinated primary afferents innervating the inflamed urinary bladder of the cat
Authors: Habler H. J. , Janig W. , Koltzenburg M.
Published: December 2017

1. The present study has investigated the receptive properties of myelinated mechanoreceptive primary afferents innervating the inflamed urinary bladder of the cat. In 15 experiments, 20 units were recorded from the dorsal and 3 from the ventral root S2. Before inflammation the afferents had no resting activity and responded consistently to increases of intravesical pressure evoked by isotonic distension or isovolumetric contractions. All units were studied before and after the onset of an acute inflammation induced by intraluminal injection of mustard (1-2.5%) or turpentine oil (50%), which are known to induce an acute cystitis. 2. Eleven out of 14 units tested with mustard oil and 5/9 units tested with turpentine oil were activated at short latency. The response could not be explained by a concomitant increase of intraluminal pressure resulting from the intravesical injection of the irritant. This suggests that a large proportion of mechanosensitive afferents has an additional chemosensitivity. 3. After removal of the irritants and with empty bladder, all afferent units exhibited irregular ongoing activity with intermittent high-frequency bursts. Such ongoing activity was entirely absent in myelinated afferents supplying the noninflamed bladder. The median rate of ongoing activity was significantly higher after mustard oil (1.65 imp/s) than after turpentine oil treatment (0.05 imp/s) 1 h after chemical stimulation. Post-hoc analysis revealed that afferents that developed high levels of ongoing activity had steeper stimulus response functions to changes of intravesical pressure before inflammation. 4. The stimulus-response function of vesical afferents changed characteristically in the inflamed bladder. Within 30 min of mustard oil treatment, the responses of some units to bladder filling was transiently enhanced, but later the units desensitized to this stimulus. However, there was no significant change of the stimulus-response function of six afferents studied before and for 2 h after induction of the inflammation. By contrast, the afferents exhibited significant increases of their mechanosensitivity after turpentine treatment. 5. In conclusion, sacral myelinated mechanoreceptive afferents supplying the urinary bladder are chemosensitive. Their receptive properties change rather uniformly when the tissue becomes inflamed, and, on the basis of these changes, it is not possible to differentiate subpopulations of primary afferents. The induction of ongoing activity and the increased responses to intravesical pressure stimuli in the inflamed organ, together with central changes that may occur under these conditions, are probably responsible for changes of bladder motility and sensations that arise during cystitis.
Effect of cytoplasmic chloride concentration on open-state preference of glycine-activated chloride channels in cultured spinal cord cells
Authors: McNiven A. I. , Martin A. R.
Published: December 2017

1. Glycine was bath-applied to outside-out patches taken from cultured mouse spinal cord neurons. Glycine-activated chloride channels had at least six open states with permeabilities of 40 (A), 68 (B), 100 (C), 145 (D), 180 (E), and 250 (F) al/s (1 attoliter = 10(-18) liter). Usually no more than two such states were seen in any given patch. The usual extracellular chloride concentration was 157 mM; chloride concentration in the electrode (on the cytoplasmic face of the patch) was varied between 7 and 170 mM, replaced at lower concentrations with either of the inert anions gluconate or methane sulphonate. 2. With normal (7 mM) chloride concentration in the electrode, openings to state D were the most probable, and the average permeability of all openings was 115 al/s. When the cytoplasmic chloride concentration was 20 mM, the most probable open state was the lower-permeability state (C), and the average permeability was 92 al/s. In symmetrical 170 mM chloride, the most probable open state was B and the mean permeability 77 al/s. 3. The glycine-activated channels had a vanishingly small permeability to fluoride. However, in experiments in which 150 mM gluconate in the pipette was replaced by fluoride, the most probable open state was B, as in the high-chloride solution. Thus the two halides had similar effects on open state preference. 4. With external and internal chloride concentrations of 7 and 157 mM, respectively, single-channel current-voltage relations could be fit with constant field relations appropriate to one or more of the permeability states.(ABSTRACT TRUNCATED AT 250 WORDS)
Changes in serotonin-induced potentials during spinal cord development
Authors: Ziskind-Conhaim L. , Seebach B. S. , Gao B. X.
Published: December 2017

1. Motoneuron responses to serotonin (5-hydroxytryptamine, 5-HT), and the growth pattern of 5-HT projections into the ventral horn were studied in the isolated spinal cord of embryonic and neonatal rats. 2. 5-HT projections first appeared in lumbar spinal cord at days 16-17 of gestation (E16-E17) and were localized in the lateral and ventral funiculi. By E18, the projections had grown into the ventral horn, and at 1-2 days after birth they were in close apposition to motoneuron somata. 3. At E16-E17, slow-rising depolarizing potentials of 1-4 mV were recorded intracellularly in lumbar motoneurons in response to bath application of 5-HT. These potentials were not apparent after E18; at that time 5-HT generated long-lasting depolarizations with an average amplitude of 6 mV, and an increase of 11% in membrane resistance. Starting at E18, 5-HT also induced high-frequency fast-rising potentials that were blocked by antagonists of glutamate, gamma-aminobutyric acid, and glycine. 4. Motoneuron responses to 5-HT increased significantly after birth, when 5-HT produced an average depolarization of 19 mV and repetitive firing of action potentials. 5. Tetrodotoxin and high Mg2+ did not reduce the amplitude of the long-lasting depolarizations, which suggested that they were produced by direct action of 5-HT on motoneuron membrane. 6. At all developmental ages, 5-HT reduced the amplitude of dorsal root-evoked potentials. The suppressed responses were neither due to 5-HT-induced depolarization nor the result of a decrease in motoneuron excitability. 7. The pharmacological profile of 5-HT-induced potentials was studied with the use of various agonists and antagonists of 5-HT. The findings indicated that the actions of 5-HT on spinal neurons were mediated via multiple 5-HT receptor subtypes. 8. Our results suggested that 5-HT excited spinal neurons before 5-HT projections grew into the ventral horn. The characteristics of 5-HT-induced potentials changed, however, at the time when the density of 5-HT projections increased in the motor nuclei.
Transient extracellular volume reduction in neural lobe of rat hypophysis in response to neural stalk stimulation in vitro and its relationship to extracellular potassium
Authors: Armstrong W. E. , Rice M. E.
Published: December 2017

1. Using ion-sensitive microelectrodes, a transient reduction in the local volume of neural lobe extracellular space was found to accompany the elevation in extracellular potassium induced by stimulation of the neural stalk. The volume decrease and potassium increase had similar stimulus-response curves when stimulus frequency was varied from 1 to 40 Hz, with maximal response at 20 Hz. The curves for stimulus duration diverged, as a near maximal potassium response was reached in 4-16 s with a 20-Hz stimulus, while the extracellular volume decrease was maximal at 64 s. 2. The volume decrease, but not the potassium increase, was strongly inhibited by lowering bath temperature and moderately inhibited by furosemide and by lowering extracellular chloride concentration. Both the volume and the potassium response were enhanced by ouabain. 3. In conclusion, shrinkage of the local extracellular space in neural lobe during nerve activity is mediated by a metabolically active process which is only partially dependent upon extracellular chloride concentration and anion-cation co-transport, but is relatively independent of Na(+)-K+ pump activity. A transient shrinkage in extracellular space during increased neurohypophysial nerve activity would be expected to play a role in hormone diffusion, ion buffering, and extracellular current flow.
Anoxia-induced LTP of isolated NMDA receptor-mediated synaptic responses
Authors: Crepel V. , Hammond C. , Krnjevic K. , Chinestra P. , Ben-Ari Y.
Published: December 2017

1. The effects of an anoxic-aglycemic episode (1-3 min) on the pharmacologically isolated N-methyl-D-aspartate (NMDA)-mediated responses were examined in CA1 pyramidal hippocampal neurons in vitro. 2. An anoxic-aglycemic episode induced a long term potentiation (LTP) of the NMDA receptor-mediated field excitatory post-synoptic potentials (EPSPs). This LTP, referred to as anoxic LTP, was observed in the presence of 1) a normal Mg2+ concentration [+40.1 +/- 5% (mean +/- SE)], 2) a low Mg2+ concentration (+52.2 +/- 10%), or 3) a Mg2+ free (+49 +/- 11%), 1 h after anoxia. 3. Bath application of D-2-amino-5-phosphonovaleric acid (D-APV, 20 microM, 15-21 min) before, during, and after the anoxic-aglycemic episode, which transiently blocked the synaptic NMDA receptor mediated response, prevented the induction of anoxic LTP. 4. The intracellularly recorded NMDA receptor-mediated EPSP was also persistently potentiated by anoxia-aglycemia (+47 +/- 4%). This potentiation was not associated with changes in membrane potential or input resistance. 5. These findings provide the first evidence that an anoxic-aglycemic episode induces an LTP of NMDA receptor-mediated responses. This potentiation may participate in the cascade of events that lead to delayed neuronal death.
A calcium-activated potassium channel causes frequency-dependent action-potential failures in a mammalian nerve terminal
Authors: Bielefeldt K. , Jackson M. B.
Published: December 2017

1. The contribution of a calcium-activated potassium channel to action-potential failure was studied in nerve terminals of the rat posterior pituitary. 2. Depolarizing current injections under current clamp were faithfully followed by action potentials for stimulation frequencies of < or = 12 Hz. Further increases in frequency resulted in action-potential failure within a few hundred milliseconds. The fraction of failures increased with stimulation frequency. This decrease in excitability was concomitant with a hyperpolarization from -57.3 +/- 1.4 to -61.3 +/- 1.4 (SE) mV. 3. The decrease in excitability was dependent on calcium influx through voltage-dependent calcium channels, because action-potential failures did not occur at frequencies < or = 30 Hz in the presence of cadmium. The dihydropyridine agonist BayK 8644 increased the fraction of failed action potentials. 4. Depolarizations from -80 to 10 mV for 3 s evoked macroscopic potassium currents with a rapidly activated, transient component and a slowly developing, noninactivating component. The late outward current was dependent on calcium influx, because it was reduced by cadmium and enhanced by BayK 8644. 5. Tetraethylammonium and 4-aminopyridine effectively blocked potassium outward currents but failed to distinguish this calcium-dependent potassium channel from the other two potassium channels in this preparation. Charybdotoxin and apamin did not affect potassium currents in this preparation. 6. In excised inside-out patches, the calcium-dependent potassium channel had a slope conductance of 193 pS. The open probability changed e-fold per 14.8 mV change in membrane potential with a calcium concentration at the cytoplasmic membrane face ([Ca]i) of 100 nM. 7. The channel was highly sensitive to [Ca]i. Depolarizations to 100 mV at 10 nM [Ca]i activated the channel half-maximally. When [Ca]i was raised to 250 nM, the voltage for half-maximal activation shifted to -16 mV. Calcium also decreased the steepness of the voltage activation curve. 8. At a constant membrane potential, pressure ejection of calcium to the cytosolic face of an excised patch activated the channel with a delay of 82 ms. This slow activation in excised patches was consistent with the slow activation of the delayed component of the macroscopic current. 9. At constant calcium concentration, the time course of activation exhibited a strong voltage dependence. Most of the channels did not inactivate during depolarizations lasting < or = 300 ms. 10. The channel exhibited complex gating, with at least two distinct open and closed states.(ABSTRACT TRUNCATED AT 400 WORDS)