bluuebunny/crossref_metadata_2025 huggingface dataset:
Regulation of pH in rat brain synaptosomes. I. Role of sodium, bicarbonate, and potassium
Authors: Sanchez-Armass S. , Martinez-Zaguilan R. , Martinez G. M. , Gillies R. J.
Published: December 2017

1. We investigated the regulation of intracellular pH (pHi) in rat brain isolated nerve terminals (synaptosomes), using fluorescence pH indicators and time-resolved fluorescence spectroscopy. 2. The resting pHi was not significantly affected by the presence or absence of HCO3-. Removal of external Na+, in the absence or presence of HCO3- caused a rapid acidification of pHi. The recovery from acid loads was primarily due to the activity of the Na+/H+ exchanger, confirming the relevance of this transport system in synaptosomes. 3. Our data revealed that in synaptosomes the activity of the Na+/H+ exchanger was not regulated by either protein kinase C or kinase A. In contrast, Ca2+ played an important role in the regulation of Na+/H+ exchanger. This was supported by the observation that 4Br-A23187 induced a Na(+)-dependent alkalinization of the resting pHi and greatly enhanced the initial rate and the degree of the recovery from acid loads. 4. In most eukaryotic cells, HCO3(-)-based transport mechanisms play an important role in pHi regulation. In synaptosomes, however, HCO3- transport is not significantly involved in pHi regulation, because the presence or absence of HCO3- does not affect resting pHi nor the rate of pHi recovery to acid loads. Further studies to address the role of Cl- and HCO3- in pHi regulation in synaptosomes are discussed in the companion paper. 5. Increasing the concentration of Ko+ also resulted in a rise of steady-state pHi by a processes that is Ca2+ and HCO3- independent. This alkalinization could be due to either K+/H+ exchanger activity, K(+)-induced depolarization, reduction of delta microH+, or a direct reduction of delta microK+. Calculated H+ driving forces suggest that the reduction in the inwardly directed H+ leak is sufficient to explain this K(+)-induced alkalinization because it changes the delta microH+ by virtue of setting the membrane potential difference (Em) to the K+ equilibrium potential (EK+).
Reduction in postsynaptic inhibition during maintained electrical stimulation of different nerves in the cat hindlimb
Authors: Heckman C. J. , Miller J. F. , Munson M. , Paul K. D. , Rymer W. Z.
Published: December 2017

1. Steady-state postsynaptic potentials (PSPs) were generated by prolonged (approximately 1 s) high-frequency (100-200 Hz) electrical stimulation of nerves in the cat hindlimb. The characteristics of these steady-state PSPs were compared for two polysynaptic afferent pathways (ipsilateral cutaneous sural vs. contralateral peroneal nerves), two animal preparations (decerebrate vs. chloralose), and two motoneuron pools (medial gastrocnemius vs. lateral gastrocnemius-soleus). 2. PSPs from both nerves usually (36 of 51 cases) contained a mixture of depolarizing and hyperpolarizing components. In all 36 cases where the PSP contained a hyperpolarizing component, a consistent qualitative pattern emerged during prolonged stimulation: the hyperpolarization reached a peak approximately 20 ms after stimulation onset and then decayed with a biphasic time course that consisted of an initial rapid phase (20–40 ms) and a later slower phase (200–400 ms) before the steady-state value was reached. This pattern occurred regardless of the differences in polysynaptic afferent pathways, animal preparations, and motoneuron pools. 3. The consistency of this overall pattern was remarkable, given the existence of several quantitative differences among the PSPs. These differences include the following: hyperpolarizing components were least common in the sural and peroneal PSPs in the decerebrate preparation. And only these sural and peroneal PSPs tended to have prolonged afterpotentials after stimulus cessation. The steady-state sural PSPs in the decerebrate preparation tended to generate the largest PSPs and, moreover, these PSPs did not follow the overall trend of having a statistically significant relation between the amplitude of the initial hyperpolarization and the amount of its decay. Finally, transient sural PSPs in lateral gastrocnemius-soleus motoneurons in the decerebrate preparation tended to have the largest hyperpolarizations. 4. To determine whether the decay of the hyperpolarization and the subsequent dominance of depolarization was due to a decreased inhibition or an increased excitation, injected current pulses were utilized to measure the changes in the cell's input resistance during the course of the synaptic input. A strong decrease in input resistance accompanied the initial period of maximal hyperpolarization (50% with respect to the resting input resistance). Input resistance then returned toward resting values as hyperpolarization faded and depolarization became dominant. However, there remained a persistent decrease in input resistance during the final phase of the PSP that amounted to < 10% of the initial decrease. These findings indicated that much of the reduction in hyperpolarization reflected a progressive decrease in synaptic efficacy for the inhibition.(ABSTRACT TRUNCATED AT 400 WORDS)
Functional properties of single neurons in the primate face primary somatosensory cortex. II. Relations with different directions of trained tongue protrusion
Authors: Lin L. D. , Murray G. M. , Sessle B. J.
Published: December 2017

1. In previous papers we have presented evidence suggesting an important role for the face primary somatosensory cortex (SI) in the fine control of tongue movements. These findings, plus our earlier evidence that many neurons in face motor cortex (MI) may exhibit firing rates related to the direction of tongue protrusion, led us to test the hypothesis that variations in the direction of a tongue-protrusion movement would be associated with variations in the activity of different face SI neurons. 2. Two monkeys were trained to perform a tongue-protrusion task in each of three directions: the task transducer was positioned at 0 degrees, 30 degrees to the left, or 30 degrees to the right from the midsagittal plane. The latter two positions were termed asymmetrical tongue-protrusion task positions. Single-neuron activity was recorded from face SI during trials of the tongue-protrusion task at each of two or three of the above positions. In addition, the mechanoreceptive field (RF) was delineated for each neuron. 3. Directional relations were found in 25 (58%) of the 43 neurons studied; this included 20 neurons showing a significant direction-by-time interaction in firing rate, i.e., the change of firing rate from the pretrial period to the task period was significantly different between different directions, and 5 showing no direction-by-time interaction but a significant difference in firing rate between different directions of the tongue-protrusion task. 4. Of the 43 neurons investigated, 21 and 20 had a RF on the tongue and lips, respectively (“tongue RF” and “lip RF” neurons), and the remaining 2 received mechanosensitive afferent inputs from other orofacial regions. There was no significant difference in the incidence of directional sensitivity between the neurons with a tongue RF and those with a lip RF (12/21 and 11/20, respectively). 5. Eight of the 25 “directional” neurons were located in area 3b and 17 in area 1. There was no significant difference in the proportion of directional neurons between areas 3b and 1. 6. The increase in discharge frequency at the preferred direction was, on the average for the 25 directional neurons, 39% over the mean discharge frequency observed during the task period for all directions of the tongue-protrusion task. Eight directional neurons showed a significant increase in firing rate during the tongue-protrusion task up to 130 ms before the onset of genioglossus electromyographic activity.(ABSTRACT TRUNCATED AT 400 WORDS)
Discrimination of the direction of motion on the human hand: a psychophysical study of stimulation parameters
Authors: Gardner E. P. , Sklar B. F.
Published: December 2017

1. In these experiments we assess the relative importance of the spatial and temporal properties of a moving tactile stimulus in determining the ability of humans to discriminate its direction of motion. Movement along the finger was simulated by applying a series of pulses to adjacent locations on the skin using the tactile array of an OPTACON stimulator. Simulated motion permitted us to vary independently the overall distance moved as well as the spacing, timing, and number of sequential stimuli. Different combinations of spatiotemporal parameters allowed us to further examine the relationship of apparent velocity of motion and sweep duration to behavioral performance. Discrimination accuracy was measured using signal detection techniques to calculate the discrimination parameter d' and PCmax, a bias-free measure of the percent correct identification of the direction of motion. 2. In experiments where the path length was constant, discriminability of the direction of motion increased as the spacing between successive pulses narrowed. Similarly, for a given interpulse spacing, the accuracy of discrimination increased linearly with distance, saturating at perfect performance. These apparent spatial effects on performance actually reflect the total number of stimuli presented to the skin rather than their proximity. Sweeps containing the same number of pulses are equally discriminable regardless of either their spacing or the total distance crossed on the skin. d' values obtained at 1.2-, 2.4-, and 4.8-mm spacings appear indistinguishable when plotted as a function of the total number of pulses in a sweep. 3. Experiments in which both the distance moved and the spacing between pulses was varied randomly confirmed that discrimination accuracy depends on the total number of pulses in a sweep rather than the spatial dimensions of the path traversed. Stimulation of only two points that mark the start and stop locations on the skin appears insufficient to enable subjects to discriminate correctly the direction of motion. Two-point stimulation elicits random performance whether the points lie 1.2 or 4.8 mm apart. Discriminability rises linearly to near-perfect performance when eight or more pulses are delivered sequentially. Extrapolation of the d' and PCmax curves suggests a mean threshold of approximately three points for 75% correct discrimination of the direction of motion across the skin. 4. The relationship of stimulus spacing to discriminability over a fixed path suggests that direction discrimination does not simply involve computation of the location of the start and stop points on the skin or their spatial disparity.(ABSTRACT TRUNCATED AT 400 WORDS)
Two separate inhibitory mechanisms shape the responses of dorsal cochlear nucleus type IV units to narrowband and wideband stimuli
Authors: Nelken I. , Young E. D.
Published: December 2017

1. The principal cells of the dorsal cochlear nucleus (DCN) are mostly inhibited by best frequency (BF) tones but are mostly excited by broadband noise (BBN), producing the so-called type IV response characteristic. The narrowband inhibitory responses can be explained by the inhibitory influence of interneurons with type II response characteristics. However, it is not clear that all the details of the type IV responses can be accounted for by this neural circuit. In particular, many type IV units are inhibited by band-reject noise (notch noise); type II units tend to be only weakly excited by these stimuli, if at all. In this paper we study the relationships between the narrowband, inhibitory and the wideband, excitatory regimens of the type IV responses and present the case for the existence of a second inhibitory source in DCN, called the wideband inhibitor (WBI) below. 2. Type IV units were studied using pure tones, noise bands arithmetically centered on BF, notch noise centered on BF, and BBN. We measured the rate-level function (response rate as function of stimulus level) for each stimulus. This paper is based on the responses of 28 type IV units. 3. Evidence for low-threshold inhibitory input to type IV units is derived from analysis of rate-level functions at sound levels just above threshold. Notch noise stimuli of the appropriate notch width produce inhibition at threshold in this regime. When BBN is presented, this inhibition appears to summate with excitation produced by energy in the band of noise centered on BF, resulting in BBN rate-level functions with decreased slope and maximum firing rate. A range of slopes and maximal firing rates is observed, but these variables are strongly correlated and they are negatively correlated with the strength of the inhibition produced by notch noise; this result supports the conclusion that a single inhibitory source is responsible for these effects. 4. By contrast, there is a weak (nonsignificant) positive correlation between the strength of the inhibitory effect of notch noise and the slope/maximal firing rate in response to narrowband stimuli, including BF tones. The contrast between this positive nonsignificant correlation and the significant negative correlation mentioned above suggests that more than one inhibitory effect operates: specifically, the type II input is responsible for inhibition by narrowband stimuli and a different inhibitory source, the WBI, produces inhibition by notch stimuli. 5. Several lines of evidence are given to show that type II units cannot produce the inhibition seen with notch noise stimuli.(ABSTRACT TRUNCATED AT 400 WORDS)
Interstitial volume changes during spreading depression (SD) and SD-like hypoxic depolarization in hippocampal tissue slices
Authors: Jing J. , Aitken P. G. , Somjen G. G.
Published: December 2017

1. Relative interstitial volume (ISV) was estimated from the concentration changes of iontophoretically administered tetramethyl- and tetraethylammonium (TMA+ and TEA+). Spreading depression (SD) was provoked by high K+, and hypoxic SD-like depolarization (HSD) was induced by withdrawing oxygen. 2. Probe ion concentrations increased dramatically and about equally during SD and HSD, except that in a few hypoxic trials signals became transiently smaller than control. Interstitial volume appeared to decrease on the average by approximately 70%. 3. The ISV that remains patent in CA1 region at the height of SD is < 4% of total tissue volume. Probe ions may occasionally have passed through cell membranes for a short time during hypoxic SD.
Lesions of the posterior commissure disable the vertical neural integrator of the primate oculomotor system
Authors: Partsalis A. M. , Highstein S. M. , Moschovakis A. K.
Published: December 2017

1. Spontaneous saccades, vestibuloocular responses (VOR), and optokinetic nystagmus were recorded in three squirrel monkeys before and after chemical or electrolytic lesion of the posterior commissure (PC). 2. PC lesions produced abnormal vertical eye movements, in particular, 1) Postsaccadic drifts, and 2) VOR gain reduction and phase advance more pronounced at lower frequencies of sinusoidal head rotation. Horizontal eye movements were much less affected (or normal). 3. We conclude that PC fibers are necessary for conveying the output of the vertical neural integrator to vertical oculomotor-neurons.
Directional selectivity in a nonspiking interneuron of the crayfish optic lobe: evaluation of a linear model
Authors: Glantz R. M.
Published: December 2017

1. Intracellular recordings, sine wave gratings, and paired flashes were used to characterize the directional selectivity (DS) of the peripheral neurons of the crayfish visual pathway. DS was observed in nonspiking tangential (Tan1) neurons of the distal medulla externa and it is expressed by the amplitude of the modulated synaptic potential elicited with drifting gratings. 2. The directional mechanism was characterized by variations in the grating contrast, spatial frequency, and temporal frequency. DS is both contrast and velocity dependent. 3. The velocity dependence of DS for fixed stimulus contrast can be described by a linear model including a delay and subtractive compare operation. This mechanism operates over the entire useful range of spatial and temporal frequencies. 4. The parameters of the linear model can be estimated from the spatiotemporal structure of the Tan1 cell receptive field. The receptive field exhibits a spatially asymmetric inhibitory subfield that is offset from the excitatory subfield by 3–5 degrees (1–2 ommatidia). The inhibition is delayed relative to excitation by 50–100 ms. 5. The contrast dependence of DS reflects an apparent nonlinearity in the mechanism that determines the null response amplitude. The preferred response magnitude is approximately linear with variations in contrast. 6. The nonlinearity observed in the null direction can in principle be attributed to either a tonic excitation at 0 contrast or a threshold for inhibition. There is evidence for both processes in the Tan1 cell visual response.
A C-fiber reflex modulated by heterotopic noxious somatic stimuli in the rat
Authors: Falinower S. , Willer J. C. , Junien J. L. , Le Bars D.
Published: December 2017

1. Electromyographic recordings were made from the biceps femoris muscle through a pair of noninsulated platinum/iridium needle electrodes in male Sprague-Dawley rats artificially ventilated and anesthetized with 0.8% halothane in a N2O-O2 mixture (2/3:1/3). The animals' ventilation, heart rates, and body temperatures were continuously monitored. Electrical stimuli (2-ms duration, 0.16 Hz) were delivered to the sural nerve territory through a pair of noninsulated platinum/iridium needle electrode inserted subcutaneously in the medial aspect of the 4th and the lateral part of the 5th toe. Such stimulation elicited a two-component reflex response in the ipsilateral biceps femoris muscle: The first had a short latency (17.5 +/- 2.3 ms), short duration (20.7 +/- 2.6 ms), and low threshold (1.5 +/- 0.6 mA), whereas the second had a longer latency (162.4 +/- 5.1 ms), longer duration (202.3 +/- 6.2 ms), and higher threshold (5.7 +/- 0.5 mA). 2. Lidocaine (0.02–0.1%; 0.1 ml), but not saline, injected subcutaneously over the proximal part of the sural nerve, produced a selective depression of the late component of the reflex response, whereas the first component remained unchanged. The conduction velocity of the afferent fibers was estimated from the stimulation needles in the sural nerve territory to the nerve's projection in the lumbar spinal cord: it was concluded that the second, late component of the reflex response was due to afferent signals transmitted via unmyelinated C-fibers, whereas the first component was related to activation of fine myelinated fibers (A delta group). 3. Electrical stimulation of the sural nerve was still able to elicit the two-component reflex responses in the ipsilateral biceps femoris muscle of chronic spinal rats, indicating that these responses were genuine reflex responses, transmitted completely through a spinal circuit. 4. The C-fiber reflex was recorded when the duration and frequency of the stimuli applied to the sural nerve varied within the 0.5- to 4-ms and 0.02- to 1-Hz ranges, respectively. It was concluded that a single 2-ms duration shock at an intensity of 1.2 times the C-fiber reflex threshold, delivered every 6 s (0.16 Hz), constituted an acceptable and optimal protocol for experiments in which the C-fiber reflex was studied as a function of time. These parameters were used throughout the subsequent experiments.(ABSTRACT TRUNCATED AT 400 WORDS)
Descending control of nonspiking local interneurons in the terminal abdominal ganglion of the crayfish
Authors: Namba H. , Nagayama T. , Hisada M.
Published: December 2017

1. Electrical stimulation of afferents innervating an exopodite causes a closing pattern of activity in the uropod motor neurons. In this reflex two distinct types of nonspiking local interneurons, posterolateral (PL) and anterolateral (AL) types, classified by their gross morphology and somata location, receive sensory inputs and control the motor output to the uropod. 2. In the sensory-motor pathway, the PL and AL nonspiking local interneurons formed opposing and parallel connections with uropod motor neurons. For example, the PL interneurons that excited the closer, reductor motor neuron by injecting depolarizing current received depolarizing postsynaptic potentials (PSPs), whereas the AL interneurons of the same output received hyperpolarizing PSPs. The PL interneurons that inhibited the reductor motor neuron received hyperpolarizing PSPs, whereas the AL interneurons of the similar output received depolarizing PSPs. 3. During fictive abdominal extension, induced by electrical stimulation of extension-evoking command fibers in the second-third abdominal connective, the uropod motor neurons show an opening pattern of activity that is opposite to the pattern elicited by sensory stimulation. Furthermore, sensory stimulation during ongoing fictive abdominal extension has little effect on the uropod motor neurons. 4. Except for the nonspiking local interneurons, the majority of other local circuit neurons, i.e., spiking local interneurons and ascending interneurons, are not driven by the descending inputs during abdominal extension. 5. A comparison of the responses of the nonspiking local interneurons to both sensory and descending inputs reveals that the majority of nonspiking local interneurons receive both inputs, but the sign of response to each is frequently opposite. This study suggests that the degree of excitability of two distinct types of PL and AL nonspiking local interneurons induced by sensory inputs changes depending on whether the crayfish is in a resting posture or is active with full extension of the abdomen. Ongoing abdominal extension in swimming or defensive crayfish would shift the gain of reflex pathways through the PL and AL interneurons, and motor response resulting from sensory inputs would be modulated.
Cones contribute to light-evoked, dopamine-mediated uncoupling of horizontal cells in the mudpuppy retina
Authors: Myhr K. L. , Dong C. J. , McReynolds J. S.
Published: December 2017

1. The relative effectiveness of adapting lights of different wave-lengths on uncoupling of horizontal cells was measured in dark-adapted mudpuppy retinas. Diffuse blue (470 nm) or red (620 nm) adapting stimuli were adjusted in intensity to be equally effective for rods or for cones. Uncoupling of horizontal cells was measured by intracellular recording of changes in their responses to spot and annulus stimuli. The intensities of the adapting light pairs were varied over 3 log units. The responses of the horizontal cells indicated that both rods and cones were stimulated by the adapting lights. 2. Relatively dim adapting lights did not produce detectable changes in horizontal cell coupling. Brighter adapting lights caused uncoupling of horizontal cells. When the brighter adapting lights were rod matched, the uncoupling effect of the 620-nm light was significantly greater than that of the 470 nm light, indicating that cones contribute to the uncoupling effect. 3. When the adapting lights were cone matched, the effects of the two wavelengths were not significantly different, but this did not rule out a rod contribution because the effective adapting lights probably produced maximal or nearly maximal, and hence equal or nearly equal, responses in rods. 4. The results indicate that cones contribute to the light-evoked uncoupling of horizontal cells in mudpuppy, although a contribution from rods could not be ruled out. Because it was shown previously that light-evoked uncoupling of horizontal cells in mudpuppy is mediated by dopamine, the results also suggest that cones contribute to the light-evoked release of dopamine.
Long-term changes in neocortical activity after chemical kindling with systemic pentylenetetrazole: an in vitro study
Authors: Barkai E. , Grossman Y. , Gutnick M. J.
Published: December 2017

1. Rats were chemically kindled by systemic administration of pentylenetetrazole (PTZ) every 48 h. An initially subthreshold dose that did not elicit a motor response when first applied caused severe epileptiform seizures when the animal was kindled. Once kindled, animals continued to respond to the initially subthreshold dose with a full-blown seizure for > 2 mo, even when regular administration ceased for > or = 1 mo. 2. In neocortical slices taken from kindled rats, low-intensity electrical stimulation evoked generation of prolonged (hundreds of milliseconds) paroxysmal extracellular field potentials and intracellular depolarizing potentials, indicating synchronized activity of large populations of neurons. This hyperexcitability usually appeared as an all-or-none event of variable latency. In a few cases it increased gradually with increasing stimulus intensity. The intensity of the paroxysmal response was greatly enhanced by application of gamma-aminobutyric acid-A (GABAa) receptor blockers to the bath. 3. Intracellular recordings revealed that PTZ-kindled cells differ from normal cells in their higher input resistance (42.4 + 13.6 vs. 26.4 + 9.2 M omega, mean +/- SE). Spikes generated by kindled cells differed significantly from those in normal cells in that they were of longer duration (1.65 + 0.3 vs. 1.40 + 0.15 ms) and had a slower maximal rate of fall (103 + 29.7 vs. 126 + 20.8 volts/s). 4. Injection of the lidocaine derivative QX-314 to the recorded neurons (100 mM) blocked the fast Na+ spikes. Under these conditions slow spikes, probably Ca2+ mediated, were evoked from the soma in neurons from kindled but not from normal cortex. 5. The role of N-methyl-D-aspartate (NMDA) receptors in generating paroxysmal events was evaluated by application of 20 microM 2-amino-5-phosphonovaleric acid, a specific blocker of this glutamate receptor type. Blockage of NMDA receptors cut short the paroxysmal field potentials but did not prevent their generation. Intracellularly recorded paroxysmal responses were also cut short but not abolished by intracellular hyperpolarization. 6. In slices from kindled animals intracellular responses in neurons of deeper layers differed markedly from those of superficial cells. In deep neurons, responses resembled those generated by neocortical neurons exposed to GABAergic blockers. A low-intensity stimulus to the white matter evoked an excitatory postsynaptic potential (EPSP) followed with variable latency by a paroxysmal depolarizing shift that reversed at suprathreshold membrane potentials and on which superimposed repetitive firing was always evident.(ABSTRACT TRUNCATED AT 400 WORDS)
Physiologically silent sodium channels in mammalian outer hair cells
Authors: Witt C. M. , Hu H. Y. , Brownell W. E. , Bertrand D.
Published: December 2017

1. Voltage-dependent properties of isolated guinea pig outer hair cells (OHCs) were investigated using whole-cell recording. An inward current was detected in approximately 10% of the cells. This inward current was identified as belonging to the voltage-activated sodium current family on the basis of its high sensitivity to tetrodotoxin and the effect of substitution of impermeant ions. Although this is the first report of a sodium current in the mammalian cochlea, it differs from the classical neuronal sodium current by having a variable magnitude from cell to cell and an inactivation that is shifted to hyperpolarized potentials. The sensory processing role of hair cells in general and outer hair cells in particular could be disrupted by the presence of a regenerative voltage-dependent current. The functional role of the OHC sodium channels is puzzling, particularly as they may be silent in vivo.
Sensory transduction of head velocity and acceleration in the toadfish horizontal semicircular canal
Authors: Rabbitt R. D. , Boyle R. , Highstein S. M.
Published: December 2017

1. Sinusoidal mechanical indentation of the long-and-slender limb of the horizontal semicircular canal and/or utricle was used to produce adequate stimulation of the labyrinth. Indentation of the canal increased, while indentation of the utricle decreased the afferent discharge rate. This follows because indentation of the canal and utricle produce oppositely directed mechanical stimuli as defined by endolymph flow, transcupular pressure, and cupular deflection. Simultaneous in-phase indentations of both the canal and utricle, with amplitudes adjusted to produce equal (but opposite) magnitudes of afferent response modulation, generate destructive interaction that minimizes the afferent modulation, whereas sinusoidal indentation 180 degrees out-of-phase generates constructive interaction that maximizes the afferent modulation. This observation correlates directly with analysis of the labyrinthine elasto-hydrodynamics which predicts that balanced in-phase indentations minimize macromechanical endolymph flow through the ampullary cross section and maximize the dilatational pressure within the ampulla acting equally on both sides of the cupula and across the labyrinthine wall. 2. Two groups of afferents are identified according to their response to balanced sinusoidal indentation of the canal limb and the utricle. In one group there is complete destructive interaction and the afferent response can be effectively nulled by adjusting the relative amplitude and phase of the two stimuli. In the second group a residual afferent response remains that cannot be nulled. The residual is described in the model as unit-specific sensitivity to dilatational pressure acting equally on both sides of the cupula.
The primate subthalamic nucleus. II. Neuronal activity in the MPTP model of parkinsonism
Authors: Bergman H. , Wichmann T. , Karmon B. , DeLong M. R.
Published: December 2017

1. The neuronal mechanisms underlying the major motor signs of Parkinson's disease were studied in the basal ganglia of parkinsonian monkeys. Three African green monkeys were systemically treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) until parkinsonian signs, including akinesia, rigidity, and a prominent 4- to 8-Hz tremor, appeared. The activity of neurons in the subthalamic nucleus (STN) and in the internal segment of the globus pallidus (GPi) was recorded before (STN, n = 220 cells; GPi, n = 175 cells) and after MPTP treatment (STN, n = 326 cells; GPi, n = 154 cells). 2. In STN the spontaneous firing rate was significantly increased from 19 +/- 10 (SD) spikes/s before to 26 +/- 15 spikes/s after MPTP treatment. Division of STN neurons recorded after MPTP treatment into cells with rhythmic bursts of discharge occurring at 4–8 Hz (as defined by autocorrelation analysis) and neurons without 4- to 8-Hz periodic activity revealed an even more prominent increase in the firing rate of the 4- to 8-Hz oscillatory neurons. 3. In GPi overall changes in the average firing rate of cells were inconsistent between different animals and behavioral states. However, the average firing rate of the subpopulation of neurons with 4- to 8-Hz periodic oscillatory activity after treatment with MPTP was significantly increased over that of all neurons before MPTP treatment (from 53 to 76 spikes/s, averaged across monkeys). 4. In the normal state the percentage of neurons with burst discharges (as defined by autocorrelation analysis) was 69% and 78% in STN and GPi, respectively. After MPTP treatment the percentage of cells that discharged in bursts was increased to 79% and 89%, respectively. At the same time the average burst duration decreased (from 121 +/- 98 to 81 +/- 99 ms in STN and from 213 +/- 120 to 146 +/- 134 ms in GPi) with no significant change in the average number of spikes per burst. 5. Periodic oscillatory neuronal activity at low frequency, highly correlated with tremor, was detected in a large number of cells in STN and GPi after MPTP treatment (average oscillation frequency 6.0 and 5.1 Hz, respectively). The autocorrelograms of spike trains of these neurons confirm that the periodic oscillatory activity was very stable. The percentage of cells with 4- to 8-Hz periodic activity significantly increased from 2% to 16% in STN and from 0.6% to 25% in GPi with the MPTP treatment.(ABSTRACT TRUNCATED AT 400 WORDS)
Modulation of the input/output function of rat piriform cortex pyramidal cells
Authors: Barkai E. , Hasselmo M. E.
Published: December 2017

1. In transverse brain slice preparations of rat piriform cortex, we characterized the repetitive firing properties of layer II pyramidal cells in control conditions (n = 78) and during perfusion of the cholinergic agonist carbachol (n = 26), with the ultimate goal of developing realistic computational simulations of the cholinergic modulation of the input/output function of these neurons. The response of neurons to prolonged (1 s) intracellular current injections was examined at a full range of current injection amplitudes, providing three-dimensional plots of firing frequency versus current amplitude versus time. 2. All neurons showed adaptation in response to intracellular current injection, with repetitive generation of action potentials at frequencies that were highest at the onset of the pulse and that decreased considerably thereafter. Substantial differences were observed between cells with regard to their rates of adaptation and the maximal number of action potentials they could generate during the current pulse. 3. The adaptation characteristics of each neuron were quantified by plotting the number of action potentials generated in 1 s as a function of the normalized current injection amplitude and measuring the area beneath this plot of the number of spikes versus current injection amplitude (S-I plot). This value was termed S-I value and allowed neurons to be plotted on a continuum including neurons showing strong adaptation (S-I value < 8.0) and neurons showing weak adaptation (S-I value > 8.0). The group showing weak adaptation contained 36% of the cells in control solution and 93.8% of the cells in 20 microM carbachol. 4. Neurons showing strong adaptation did not differ significantly from neurons showing weak adaptation in control conditions in measurements of resting potential, input resistance, threshold, and spike amplitude. Only a small difference was found in frequencies of firing measured soon after pulse onset (after 100 ms). This implies that differences in S-I values are primarily due to different rates of adaptation in later parts of the response. 5. Perfusion with solution containing the cholinergic agonist carbachol (2–100 microM) or 0 Ca2+ and 200 microM cadmium resulted in a substantial increase in the S-I values of neurons showing strong adaptation but had only a small effect on their initial firing rates. The effect on weakly adapting cells was smaller. In the presence of 20 microM carbachol, neurons showed a distribution shifted predominantly toward weak adaptation (n = 26).(ABSTRACT TRUNCATED AT 400 WORDS)
Effects of insulin and hypoglycemia on the auditory brain stem response in humans
Authors: Kern W. , Kerner W. , Pietrowsky R. , Fehm H. L. , Born J.
Published: December 2017

1. This study aimed to differentiate effects of insulin and hypoglycemia on sensory brain stem functions in humans. Auditory brain stem responses (ABR) were examined in 30 healthy men during euglycemia and after 20 and 50 min of steady-state hypoglycemia of 2.6 mM induced with human insulin (HI) in one session and porcine insulin (PI) in another session. 2. Levels of blood glucose and serum insulin were identical in both sessions during HI and PI infusion. 3. Hypoglycemia increased interpeak latencies III–V (+71 microseconds; P < 0.001) and I–V (+123 microseconds; P < 0.001), whereas changes in the latency of wave I were not significant. 4. After 20 min of constant hypoglycemia, increases in the interpeak latencies I–V and III–V were significantly more pronounced during infusion of PI than HI. These differences disappeared with time spent in hypoglycemia, i.e., after 50 min of hypoglycemia. 5. Apart from the delaying effect of hypoglycemia on neuronal transmission within the sensory brain stem, the results provide evidence for a separate influence of insulin on these functions.
Identification of muscle afferents subserving sensation of deep pain in humans
Authors: Simone D. A. , Marchettini P. , Caputi G. , Ochoa J. L.
Published: December 2017

1. Intraneural microstimulation (INMS) and microneurography were used in combination to stimulate and record from muscle nociceptor primary afferent fibers of the common peroneal nerve of healthy volunteers. When pain evoked by INMS was projected to muscle, afferent activity could be evoked by innocuous and noxious pressure applied within the projected painful area. Conduction velocity of single fibers was determined by stimulating the receptive fields (RFs) electrically via needle electrodes inserted into the RF and measuring conduction latency and distance between the RF and recording electrode. 2. Pain projected to muscle during INMS trains 5–10 s in duration at threshold intensity for pain sensation was typically described as cramping and was well localized. Subjects mapped the area of the painful projected field (PF) over the skin using a pointer. 3. Fourteen slowly adaping mechanoreceptors with RF in muscle and with moderate to high receptor threshold were identified within or near the painful PF. Conduction velocities were in the range of Group III (n = 8) and Group IV (n = 6) fibers. Mean RF areas of Group III and Group IV afferents, determined by applying pressure percutaneously, were 2.71 +/- 1.14 (SE) cm2 and 3.40 +/- 1.08 (SE) cm2, respectively. Only one Group III afferent unit exhibited spontaneous activity (< 1 Hz). 4. One additional high-threshold mechanoreceptor was identified, with its RF located in the extensor tendon at the base of the big toe. This fiber had a conduction velocity of 32 m/s. During INMS, a well-localized sharp pain was projected to the tendon.(ABSTRACT TRUNCATED AT 250 WORDS)
Hypoglossal neural activity during ingestion and rejection in the awake rat
Authors: Dinardo L. A. , Travers J. B.
Published: December 2017

1. The activity of 34 hypoglossal (mXII) neurons was characterized during the ingestion and rejection of gustatory stimuli in the awake rat. Intraoral infusions of water, sucrose, sodium chloride, or hydrochloric acid initiated ingestion responses; infusions of quinine monohydrochloride initiated rejection responses. Electromyographic (EMG) activity from three oropharyngeal muscles monitored the occurrence of lick cycles and swallows (ingestion) and gape cycles (rejection). In addition, the orofacial region was videotaped to provide an independent assessment of lingual and jaw movements in relation to neural activity. 2. EMG activity during lick and gape cycles was quantified by calculating the duration, magnitude, and peak time of muscle contractions. Lick and gape cycles produced highly differentiated patterns of activity from jaw-opener (anterior digastric, AD), lingual protrudor (geniohyoid, GEN), and lingual retractor (styloglossus, STY) muscles. Lick cycles were characterized by an alternating two-phase sequence of protrusion-retraction; gape cycles by an initial coactivation of both lingual muscles (phase I), followed by a sequence of protrusion (phase II) and retraction (phase III). Contraction durations were significantly longer during gape cycles compared with lick cycles for the AD (Xlick +/- 59 ms; Xgape +/- 134 ms, means +/- SD), GEN (Xlick +/- 77 ms; Xgape +/- 200 ms), and STY (Xlick +/- 93 ms; Xgape +/- 220 ms) muscles. 3. Thirty-one out of 34 mXII neurons were functionally classified as protrudor- or retractor-related by cross-correlating anterior digastric EMG activity with neural activity during licking. Fourteen out of 34 neurons were protrudor-related, 17/34 were retractor-related. These classifications were largely consistent with the results from an analysis of a subset of cells (n = 14) that directly compared neural activity with videotaped records of visible tongue movements. 4. The magnitude of mXII activity during ingestion and rejection was compared by determining the mean number of spikes per lick, gape, and swallow for each neuron. Five out of 14 (36%) protrudor-related and 10/17 (59%) retractor-related cells had significant increases in activity during gape responses compared with the number of spikes per lick cycle. This increased activity of mXII neurons was consistent with the more robust lingual motor activity during the gape response. Two protrudor-related and three retractor-related neurons showed significant decreases in activity during gape responses. Although a similar proportion of mXII neurons exhibited decreases in activity during swallows compared with licks (3 protrudor- and 1 retractor-related), fewer mXII neurons (1 protrudor- and 1 retractor-related) showed increased activity during swallows.(ABSTRACT TRUNCATED AT 400 WORDS)
Substance P elevates intracellular calcium in both neurons and glial cells from the dorsal horn of the spinal cord
Authors: Heath M. J. , Womack M. D. , MacDermott A. B.
Published: December 2017

1. We used microfluorimetric measurement of [Ca2+]i to identify substance P-sensitive cells acutely isolated from the dorsal horn of neonatal rats. We then used morphological, physiological, and immunocytochemical criteria to delineate two distinct populations of substance P-sensitive dorsal horn cells. 2. One population of cells with small-diameter cell bodies and many fine processes responds to substance P by releasing Ca2+ from internal stores. Many of these cells express the O4 surface antigen, and are thus likely to be glial cells, probably from the oligodendrocyte lineage. None of the cells with glial attributes respond to N-methyl-D-aspartate (NMDA), providing further evidence that they are nonneuronal. 3. In a second population of dorsal horn cells, substance P elevates [Ca2+]i by promoting Ca2+ entry. This class of cells is morphologically distinct from substance P-sensitive glial cells in that it exhibits large-diameter cell bodies, has smooth tapering processes, and is sensitive to NMDA. This second class of cells is therefore likely to consist of neurons. 4. Consistent with the identification of different mechanisms of Ca2+ elevation in the two cell types, the kinetics of the substance P-evoked release of Ca2+ in glial cells is very different than the kinetics of the Ca(2+)-entry response evoked in neurons. The glial cell response had a rapid average rate of rise (mean = 260 +/- 105 nM/s) and relatively brief duration (mean = 7.6 +/- 2.2 s) whereas the neuronal response had a much slower rate of rise (mean = 10 +/- 9 nM/s) with a much longer duration.(ABSTRACT TRUNCATED AT 250 WORDS)
Intersegmental and local interneurons in the metathorax of the stick insect Carausius morosus that monitor middle leg position
Authors: Brunn D. E. , Dean J.
Published: December 2017

1. In the stick insect, proprioceptive information from the middle leg is used to define the target for the swing movement of the adjacent rear leg ("targeting behavior"). To investigate the underlying neural circuits, intracellular recordings were made in the ganglion controlling the rear leg, the metathoracic ganglion, while systematically moving the tarsus of the middle leg. 2. Several intersegmental interneurons and one local interneuron were identified as possible contributors to the targeting behavior. The intersegmental interneurons code the position of the middle leg tarsus in a highly simplified manner: test movements of the middle leg in the dorsal, lateral, and caudal directions from the standard starting position at right angles to the thorax elicit phasic-tonic responses in three different intersegmental neurons. The response in each interneuron actually reflects the movement and position at only one joint of the middle leg: for the neurons responding primarily to movement in the caudal, dorsal, and lateral test directions, the adequate stimulus is movement at the subcoxal joint, the coxa-trochanter joint, and the femur-tibia joint, respectively. 3. The metathoracic local interneuron integrates information from ipsilateral middle and rear legs in such a way as to provide an approximate measure of the distance between the two tarsi in the longitudinal direction. It is depolarized in a phasic-tonic manner both by caudal movements of the ipsilateral middle leg and by rostral movements of the ipsilateral rear leg. The adequate stimulus in each case is the change in the angle at the subcoxal joint of the leg moved. Depolarization of this neuron activates retractor motoneurons, which is consistent with a role in terminating the swing movement. 4. Altogether the results indicate first, that the targeting behavior could be controlled by very few intersegmental channels and, second, that the nervous system encodes the position of the middle leg tarsus in terms of joint angles rather than in abstract, body-centered coordinates.
Effect of longer periods of dark rearing on NMDA receptors in cat visual cortex
Authors: Czepita D. , Reid S. N. , Daw N. W.
Published: December 2017

1. Cats were reared in the dark to 3, 5, and 11 mo. We studied the N-methyl-D-aspartate (NMDA) receptor contribution to the visual response in the cortex, defined as the percentage reduction in visual response after application of 2-amino-5-phosphonovaleric acid (APV). We also studied the firing rate in response to the optimal visual stimulus and the spontaneous activity. We made comparisons of all these properties between light-reared and dark-reared animals. 2. The NMDA receptor contribution to the visual response in layers IV, V, and VI of dark-reared animals was substantially above that in light-reared animals at all ages tested. 3. The specificity of receptive field properties in dark-reared animals showed some degeneration between 6 wk and 3 mo of age. At > or = 3 mo, almost no cells were specific for orientation and direction of movement. 4. Firing rate was lower in dark-reared animals at all ages, suggesting a decrease in excitatory drive to the visual cortex. 5. Spontaneous activity was equal in dark- and light-reared animals, suggesting that the overall level of activity (including visual responses as well as spontaneous activity) in light-reared animals is higher than in dark-reared animals. This should tend to upregulate glutamate receptors in general in dark-reared animals.