bluuebunny/crossref_metadata_2025 huggingface dataset:
Selective Stimulation of Cat Sciatic Nerve Using an Array of Varying-Length Microelectrodes
Authors: Branner Almut , Stein Richard B. , Normann Richard A.
Published: December 2017

Restoration of motor function to individuals who have had spinal cord injuries or stroke has been hampered by the lack of an interface to the peripheral nervous system. A suitable interface should provide selective stimulation of a large number of individual muscle groups with graded recruitment of force. We have developed a new neural interface, the Utah Slanted Electrode Array (USEA), that was designed to be implanted into peripheral nerves. Its goal is to provide such an interface that could be useful in rehabilitation as well as neuroscience applications. In this study, the stimulation capabilities of the USEA were evaluated in acute experiments in cat sciatic nerve. The recruitment properties and the selectivity of stimulation were examined by determining the target muscles excited by stimulation via each of the 100 electrodes in the array and using force transducers to record the force produced in these muscles. It is shown in the results that groups of up to 15 electrodes were inserted into individual fascicles. Stimulation slightly above threshold was selective to one muscle group for most individual electrodes. At higher currents, co-activation of agonist but not antagonist muscles was observed in some instances. Recruitment curves for the electrode array were broader with twitch thresholds starting at much lower currents than for cuff electrodes. In these experiments, it is also shown that certain combinations of electrode pairs, inserted into an individual fascicle, excite fiber populations with substantial overlap, whereas other pairs appear to address independent populations. We conclude that the USEA permits more selective stimulation at much lower current intensities with more graded recruitment of individual muscles than is achieved by conventional cuff electrodes.
Long-Term Correlations in the Spike Trains of Medullary Sympathetic Neurons
Authors: Lewis Craig D. , Gebber Gerard L. , Larsen Peter D. , Barman Susan M.
Published: December 2017

Fano factor analysis was used to characterize the spike trains of single medullary neurons with sympathetic nerve–related activity in cats that were decerebrate or anesthetized with Dial-urethan or urethan. For this purpose, values (Fano factor) of the variance of the number of extracellularly recorded spikes divided by the mean number of spikes were calculated for window sizes of systematically varied length. For window sizes ≤10 ms, the Fano factor was close to one, as expected for a Bernoulli process with a low probability of success. The Fano factor dipped below one as the window size approached the shortest interspike interval (ISI) and reached its nadir at window sizes near the modal ISI. The extent of the dip reflected the shape (skewness) of the ISI histogram with the dip being smallest for the most asymmetric distributions. Most importantly, for a wide range of window sizes exceeding the modal ISI, the Fano factor curve took the form of a power law function. This was the case independent of the component (cardiac related, 10 Hz, or 2–6 Hz) of inferior cardiac sympathetic nerve discharge to which unit activity was correlated or the medullary region (lateral tegmental field, raphe, caudal and rostral ventrolateral medulla) in which the neuron was located. The power law relationship in the Fano factor curves was eliminated by randomly shuffling the ISIs even though the distribution of the intervals was unchanged. Thus the power law relationship arose from long-term correlations among ISIs that were disrupted by shuffling the data. The presence of long-term correlations across different time scales reflects the property of statistical self-similarity that is characteristic of fractal processes. In most cases, we found that mean ISI and variance for individual spike trains increased as a function of the number of intervals counted. This can be attributed to the clustering of long and short ISIs, which also is an inherent property of fractal time series. We conclude that the spike trains of brain stem sympathetic neurons have fractal properties.
Analysis of Firing Correlations Between Sympathetic Premotor Neuron Pairs in Anesthetized Cats
Authors: McAllen R. M. , Trevaks D. , Allen A. M.
Published: December 2017

The activity of sympathetic premotor neurons in the rostral ventrolateral medulla (subretrofacial nucleus) supports sympathetic vasomotor tone, but the factors that drive these premotor neurons' activity have not been determined. This study examines whether either direct interconnections between subretrofacial neurons or synchronizing common inputs to them are important for generating their tonic activity. Simultaneous extracellular single-unit recordings were made from 32 pairs of sympathetic premotor neurons in the subretrofacial nucleus of chloralose-anesthetized cats. Paired spike trains were either separated by spike shape from a single-electrode recording (14 pairs) or recorded from two electrodes less than 250 μm apart (18 pairs). All neurons were inhibited by carotid baroreceptor stimulation and most had a spinal axon proven by antidromic stimulation from the spinal cord. Autocorrelation, inter-spike interval, and cardiac cycle-triggered histograms were constructed from the spontaneous activity of each neuron, and cross-correlation histograms covering several time scales were generated for each neuron pair. No significant peaks or troughs were found in short-term cross-correlation histograms (2 ms bins, ±100 ms range), providing no support for important local synaptic interactions. On an intermediate time scale (20 ms bins, ±1 s range), cross-correlation revealed two patterns indicating shared, synchronizing inputs. Repeating peaks and troughs (19/32 pairs) were due to the two neurons' common cardiac rhythmicity, of presumed baroreceptor origin. Single, zero time-spanning peaks of 40–180 ms width were seen in 5/32 cases. Calculations based on the prevalence and strength of these synchronizing inputs indicate that most of the ensemble spike activity of the subretrofacial neuron population is derived from asynchronous sources (be they intrinsic or extrinsic). If synchronizing sources such as neuronal oscillators were responsible for more than a minor part of the drive, they would be multiple, dispersed, and weak.
Dopamine-Mediated Volume Transmission in Midbrain Is Regulated by Distinct Extracellular Geometry and Uptake
Authors: Cragg Stephanie J. , Nicholson Charles , Kume-Kick June , Tao Lian , Rice Margaret E.
Published: December 2017

Somatodendritic release of dopamine (DA) in midbrain is, at least in part, nonsynaptic; moreover, midbrain DA receptors are predominantly extrasynaptic. Thus somatodendritic DA mediates volume transmission, with an efficacy regulated by the diffusion and uptake characteristics of the local extracellular microenvironment. Here, we quantitatively evaluated diffusion and uptake in substantia nigra pars compacta (SNc) and reticulata (SNr), ventral tegmental area (VTA), and cerebral cortex in guinea pig brain slices. The geometric parameters that govern diffusion, extracellular volume fraction (α) and tortuosity (λ), together with linear uptake ( k′), were determined for tetramethylammonium (TMA+), and for DA, using point-source diffusion combined with ion-selective and carbon-fiber microelectrodes. TMA+-diffusion measurements revealed a large α of 30% in SNc, SNr, and VTA, which was significantly higher than the 22% in cortex. Values for λ and k′ for TMA+ were similar among regions. Point-source DA-diffusion curves fitted theory well with linear uptake, with significantly higher values of k′ for DA in SNc and VTA (0.08–0.09 s− 1) than in SNr (0.006 s− 1), where DA processes are sparser. Inhibition of DA uptake by GBR-12909 caused a greater decrease in k′ in SNc than in VTA. In addition, DA uptake was slightly decreased by the norepinephrine transport inhibitor, desipramine in both regions, although this was statistically significant only in VTA. We used these data to model the radius of influence of DA in midbrain. Simulated release from a 20-vesicle point source produced DA concentrations sufficient for receptor activation up to 20 μm away with a DA half-life at this distance of several hundred milliseconds. Most importantly, this model showed that diffusion rather than uptake was the most important determinant of DA time course in midbrain, which contrasts strikingly with the striatum where uptake dominates. The issues considered here, while specific for DA in midbrain, illustrate fundamental biophysical properties relevant for all extracellular communication.
Characterization of Tactile Afferent Fibers in the Hand of the Marmoset Monkey
Authors: Coleman G. T. , Bahramali H. , Zhang H. Q. , Rowe M. J.
Published: December 2017

The marmoset monkey, Callithrix jacchus, has increasingly been the subject of experiments for the analysis of somatosensory system function in simian primates. However, as response properties of the mechanoreceptive afferent fibers supplying the skin have not been characterized for this primate, the present study was undertaken to classify fibers innervating the glabrous skin of the marmoset hand and determine whether they resembled those described for other mammalian species, including cat, macaque monkey, and human subjects. Forty-seven tactile afferent fibers with receptive fields (RFs) on the glabrous skin of the hand were isolated in fine median and ulnar nerve strands. Controlled tactile stimuli, including static indentation and skin vibration, were used to classify fibers. Twenty-six (55%) responded to static indentation in a sustained manner and were designated slowly adapting (SA) fibers, while 21 (45%) were selectively sensitive to the dynamic components of the stimulus. The SA fibers had well-defined boundaries to their RFs, lacked spontaneous activity in most cases (23/26 fibers), had an irregular pattern of discharge to static skin indentation, and displayed graded response levels as a function of indentation amplitude, attributes that were consistent with the properties of slowly adapting type I (SAI) fibers described in other species. The dynamically sensitive afferent fibers could be subdivided into two distinct functional classes, based on their responses to vibrotactile stimulation. The majority (15/21) responded best to lower frequency vibration (∼10–50 Hz) and had small RFs, whereas the second class responded preferentially to higher frequency vibration (50–700 Hz) with maximal sensitivity at ∼200–300 Hz. These two classes resembled, respectively, the rapidly adapting (RA) and Pacinian corpuscle–related (PC) fiber classes found in other species, and like them, responded to vibration with tightly phase-locked patterns of response over a wide range of frequencies. The results demonstrate that the functional classes of tactile afferent fibers that supply the glabrous skin in the marmoset monkey appear to correspond with those described previously for the cat and macaque monkey, and are similar to those supplying the human hand and fingers, although the SA fibers in the human hand appear to fall into two classes, the SAI and SAII fibers. With the increasing use of the marmoset monkey as a primate model for somatosensory system studies, these data now allow tactile neurons identified at central locations, such as the cerebral cortex and thalamus, to be classified in relation to inputs from the peripheral classes identified in the present study.
Synaptically Released Neurotransmitter Fails to Desensitize Postsynaptic GABAA Receptors in Cerebellar Cultures
Authors: Mellor J. R. , Randall A. D.
Published: December 2017

GABA concentration jump experiments performed on membrane patches predict that postsynaptic GABAAreceptors will become desensitized following the release of the contents of a single GABA-containing synaptic vesicle. To examine this we used a single synaptic bouton stimulation technique to directly examine whether postsynaptic GABAA receptors in cultured cerebellar granule cells exhibit transmitter-induced desensitization. In a large number of recordings, no evidence was found for desensitization of postsynaptic GABAAreceptors by vesicularly released transmitter. This was the case even when as many as 40 vesicles were released from a single bouton within 1.5 s. In addition, postsynaptic depolarization and application of the benzodiazepine flunitrazepam, manipulations previously shown to enhance desensitization of GABAA receptors, failed to unmask transmitter-induced desensitization. In contrast, a single 2- to 3-s application of a high concentration of exogenous GABA was able to depress synaptic responsiveness for up to 70 s. Furthermore, pharmacological depletion of GABA eliminated inhibitory synaptic communication, suggesting that GABA is the transmitter and the desensitization-resistant inhibitory postsynaptic currents are not mediated by a “nondesensitizing” ligand such as β-alanine. Overall our data indicate that a specific desensitization-resistant population of GABAA receptors are present at postsynaptic sites on cultured cerebellar granule cells.
Contrast-Dependent Nonlinearities Arise Locally in a Model of Contrast-Invariant Orientation Tuning
Authors: Kayser Andrew , Priebe Nicholas J. , Miller Kenneth D.
Published: December 2017

We study a recently proposed “correlation-based,” push-pull model of the circuitry of layer 4 of cat visual cortex. This model was previously shown to explain the contrast-invariance of cortical orientation tuning. Here we show that it can simultaneously account for several contrast-dependent (c-d) “nonlinearities” in cortical responses. These include an advance with increasing contrast in the temporal phase of response to a sinusoidally modulated stimulus; a change in shape of the temporal frequency tuning curve, so that higher temporal frequencies may give little or no response at low contrast but reasonable responses at high contrast; and contrast saturation that occurs at lower contrasts in cortex than in the lateral geniculate nucleus (LGN). In the context of the model circuit, these properties arise from a mixture of nonlinear cellular and synaptic mechanisms: short-term synaptic depression, spike-rate adaptation, contrast-induced changes in cellular conductance, and the nonzero spike threshold. The former three mechanisms are sufficient to explain the experimentally observed increase in c-d phase advance in cortex relative to LGN. The c-d changes in temporal frequency tuning arise as a threshold effect: voltage modulations in response to higher-frequency inputs are only slightly above threshold at lower contrast, but become robustly suprathreshold at higher contrast. The other three nonlinear mechanisms also play a crucial role in this result, allowing contrast dependence of temporal frequency tuning to coexist with contrast-invariance of orientation tuning. Contrast saturation, and the observation that responses to stimuli of increasing temporal frequency saturate at increasingly high contrasts, can be induced both by the model's push-pull inhibition and by synaptic depression. Previous proposals explained these nonlinear response properties by assuming contrast-invariant orientation tuning as a starting point, and adding normalization by shunting inhibition derived equally from cells of all preferred orientations. The present proposal simultaneously explains both contrast-invariant orientation tuning and these contrast-dependent nonlinearities and requires only processing that is local in orientation, in agreement with intracellular measurements.
A Pertussis Toxin-Sensitive 8-Lipoxygenase Pathway Is Activated by a Nicotinic Acetylcholine Receptor inAplysiaNeurons
Authors: Tieman Tamara L. , Steel Douglas J. , Gor Yelena , Kehoe Jacsue , Schwartz James H. , Feinmark Steven J.
Published: December 2017

Acetylcholine (ACh) activates two types of chloride conductances in Aplysia neurons that can be distinguished by their kinetics and pharmacology. One is a rapidly desensitizing current that is blocked by α-conotoxin-ImI and the other is a sustained current that is insensitive to the toxin. These currents are differentially expressed in Aplysia neurons. We report here that neurons that respond to ACh with a sustained chloride conductance also generate 8-lipoxygenase metabolites. The sustained chloride conductance and the activation of 8-lipoxygenase have similar pharmacological profiles. Both are stimulated by suberyldicholine and nicotine, and both are inhibited by α-bungarotoxin. Like the sustained chloride conductance, the activation of 8-lipoxygenase is not blocked by α-conotoxin-ImI. In spite of the similarities between the metabolic and electrophysiological responses, the generation of 8-lipoxygenase metabolites does not appear to depend on the ion current since an influx of chloride ions is neither necessary nor sufficient for the formation of the lipid metabolites. In addition, the application of pertussis toxin blocked the ACh-activated release of arachidonic acid and the subsequent production of 8-lipoxygenase metabolites, yet the ACh-induced activation of the chloride conductance is not dependent on a G protein. Our results are consistent with the idea that the nicotinic ACh receptor that activates the sustained chloride conductance can, independent of the chloride ion influx, initiate lipid messenger synthesis.
Odor-Stimulated Phosphatidylinositol 3-Kinase in Lobster Olfactory Receptor Cells
Authors: Zhainazarov Asylbek B. , Doolin Richard , Herlihy John-David , Ache Barry W.
Published: December 2017

Two antagonists of phosphoinositide 3-OH kinases (PI3Ks), LY294002 and Wortmannin, reduced the magnitude of the receptor potential in lobster olfactory receptor neurons (ORNs) recorded by patch clamping the cells in vivo. An antibody directed against the c-terminus of human PI3K-P110β detected a molecule of predicted size in the outer dendrites of the ORNs. Two 3-phosphoinositides, PI(3,4)P2(1–4 μM) and PI(3,4,5)P3(1–4 μM) applied to the cytoplasmic side of inside-out patches taken from cultured lobster ORNs, reversibly activated a Na+-gated channel previously implicated in the transduction cascade in these cells. 3-Phosphoinositides were the most effective phosphoinositide (1 μM) in enhancing the open probability of the channel. Collectively, these results implicate 3-phosphoinositides in lobster olfactory transduction and raise the need to consider the 3-phosphoinositide pathway in olfactory transduction.
Hypoxia-Induced Respiratory Patterned Activity inLymnaeaOriginates at the Periphery
Authors: Inoue T. , Haque Z. , Lukowiak K. , Syed N. I.
Published: December 2017

Respiration in Lymnaeais a hypoxia-driven rhythmic behavior, which is controlled by an identified network of central pattern generating (CPG) neurons. However, the precise site(s) (i.e., central or peripheral) at which hypoxia acts and the cellular mechanisms by which the respiratory chemosensory drive is conveyed to the CPG were previously unknown. Using semi-intact and isolated ganglionic preparations, we provide the first direct evidence that the hypoxia-induced respiratory drive originates at the periphery (not within the central ring ganglia) and that it is conveyed to the CPG neurons via the right pedal dorsal neuron 1 (RPeD1). The respiratory discharge frequency increased when the periphery, but not the CNS, was made hypoxic. We found that in the semi-intact preparations, the frequency of spontaneously occurring respiratory bursts was significantly lower than in isolated ganglionic preparations. Thus the periphery exerts a suppressive regulatory control on respiratory discharges in the intact animal. Moreover, both anoxia (0% O2) and hypercapnia (10% CO2) produce a reduction in respiratory discharges in semi-intact, but not isolated preparations. However, the effects of CO2may be mediated through pH changes of the perfusate. Finally, we demonstrate that chronic exposure of the animals to hypoxia (90% N2), prior to intracellular recordings, significantly enhanced the rate of spontaneously occurring respiratory discharges in semi-intact preparations, even if they were maintained in normoxic saline for several hours. Moreover, we demonstrate that the peripherally originated hypoxia signal is likely conveyed to the CPG neurons via RPeD1. In summary, the data presented in this study demonstrate the important role played by the periphery and the RPeD1 neuron in regulating respiration in response to hypoxia in Lymnaea.
Gadolinium Reduces AMPA Receptor Desensitization and Deactivation in Hippocampal Neurons
Authors: Lei Saobo , MacDonald John F.
Published: December 2017

The actions of the trivalent cation Gd3+ on whole cell AMPA receptor-mediated currents were studied in isolated hippocampal neurons, in nucleated or outside-out patches taken from cultured hippocampal neurons, and on miniature excitatory postsynaptic currents (mEPSCs) recorded in cultured hippocampal neurons. Glutamate, AMPA, or kainate was employed to activate AMPA receptors. Applications of relatively low concentrations of Gd3+ (0.1–10 μM) substantially enhanced steady-state whole cell glutamate and kainate-evoked currents without altering peak currents, suggesting that desensitization was reduced. However, higher concentrations (>30 μM) depressed steady-state currents, indicating an underlying inhibition of channel activity. Lower concentrations of Gd3+also increased the potency of peak glutamate-evoked currents without altering that of steady-state currents. An ultrafast perfusion system and nucleated patches were then used to better resolve peak glutamate-evoked currents. Low concentrations of Gd3+ reduced peak currents, enhanced steady-state currents, and slowed the onset of desensitization, providing further evidence that this cation reduces desensitization. In the presence of cyclothiazide, a compound that blocks desensitization, a low concentration Gd3+ inhibited both peak and steady-state currents, indicating that Gd3+ both reduces desensitization and inhibits these currents. Gd3+ reduced the probability of channel opening at the peak of the currents but did not alter the single channel conductance calculated using nonstationary variance analysis. Recovery from desensitization was enhanced, and glutamate-evoked current activation and deactivation were slowed by Gd3+. The Gd3+-induced reduction in desensitization did not require the presence of the GluR2 subunit as this effect was seen in hippocampal neurons from GluR2 null-mutant mice. Gd3+ reduced the time course of decay of mEPSCs perhaps as a consequence of its slowing of AMPA receptor deactivation although an increase in the frequency of mEPSCs also suggested enhanced presynaptic release of transmitter. These results demonstrate that Gd3+ potently reduces AMPA receptor desensitization and mimics a number of the properties of the positive modulators of AMPA receptor desensitization such as cyclothiazide.
Developmental Changes in Trial-to-Trial Variations in Whisker Barrel Responses Studied Using Intrinsic Optical Imaging: Comparison Between Normal and De-Whiskered Rats
Authors: Yazawa Itaru , Sasaki Shinichi , Mochida Hiraku , Kamino Kohtaro , Momose-Sato Yoko , Sato Katsushige
Published: December 2017

We used an intrinsic optical imaging technique to examine postnatal developmental changes in the rat barrel response to a single whisker movement. We compared the optical response patterns between control and de-whiskered rats, from which whiskers were removed except for the D1 whisker just after birth. Barrel responses were evoked by D1-whisker movement stimulation, and the intrinsic optical signals were detected from the somatosensory cortex through the dura mater. In the control rats, the area of the barrel response decreased gradually as postnatal development proceeded from 2 to 7 wk, until reaching the adult pattern. On the other hand, in the de-whiskered rats, the barrel response area did not change during development and showed a larger size than in the control rats. We also compared the trial-to-trial variations in the barrel responses between the two groups. In the control rats, trial-to-trial variations in the optical responses were observed under the same conditions of whisker stimulation, and the extent of the variations decreased with postnatal development up to 7 wk. In the de-whiskered rats, trial-to-trial variations were also observed, but the extent was larger and unchanged during development. In both groups, the positions of the response area were the same with respect to the bregma. These results suggest that the decrease in the area and variations in the optical responses are caused by interactions of the corresponding whisker barrel with neighboring barrels and that these interactions are necessary for the developmental stabilization of the intracortical horizontal connections, which are widespread and have high plasticity in early postnatal periods.
Intrinsic Optical Signals in Respiratory Brain Stem Regions of Mice: Neurotransmitters, Neuromodulators, and Metabolic Stress
Authors: Haller M. , Mironov S. L. , Richter D. W.
Published: December 2017

In the rhythmic brain stem slice preparation, spontaneous respiratory activity is generated endogenously and can be recorded as output activity from hypoglossal XII rootlets. Here we combine these recordings with measurements of the intrinsic optical signal (IOS) of cells in the regions of the periambigual region and nucleus hypoglossus of the rhythmic slice preparation. The IOS, which reflects changes of infrared light transmittance and scattering, has been previously employed as an indirect sensor for activity-related changes in cell metabolism. The IOS is believed to be primarily caused by cell volume changes, but it has also been associated with other morphological changes such as dendritic beading during prolonged neuronal excitation or mitochondrial swelling. An increase of the extracellular K+concentration from 3 to 9 mM, as well as superfusion with hypotonic solution induced a marked increase of the IOS, whereas a decrease in extracellular K+or superfusion with hypertonic solution had the opposite effect. During tissue anoxia, elicited by superfusion of N2-gassed solution, the biphasic response of the respiratory activity was accompanied by a continuous rise in the IOS. On reoxygenation, the IOS returned to control levels. Cells located at the surface of the slice were observed to swell during periods of anoxia. The region of the nucleus hypoglossus exhibited faster and larger IOS changes than the periambigual region, which presumably reflects differences in sensitivities of these neurons to metabolic stress. To analyze the components of the hypoxic IOS response, we investigated the IOS after application of neurotransmitters known to be released in increasing amounts during hypoxia. Indeed, glutamate application induced an IOS increase, whereas adenosine slightly reduced the IOS. The IOS response to hypoxia was diminished after application of glutamate uptake blockers, indicating that glutamate contributes to the hypoxic IOS. Blockade of the Na+/K+-ATPase by ouabain did not provoke a hypoxia-like IOS change. The influences of KATPchannels were analyzed, because they contribute significantly to the modulation of neuronal excitability during hypoxia. IOS responses obtained during manipulation of KATPchannel activity could be explained only by implicating mitochondrial volume changes mediated by mitochondrial KATPchannels. In conclusion, the hypoxic IOS response can be interpreted as a result of cell and mitochondrial swelling. Cell swelling can be attributed to hypoxic release of neurotransmitters and neuromodulators and to inhibition of Na+/K+-pump activity.
Patterns of Locomotor Drive to Motoneurons and Last-Order Interneurons: Clues to the Structure of the CPG
Authors: Burke R. E. , Degtyarenko A. M. , Simon E. S.
Published: December 2017

We have examined the linkage between patterns of activity in several hindlimb motor pools and the modulation of oligosynaptic cutaneous reflex pathways during fictive locomotion in decerebrate unanesthetized cats to assess the notion that such linkages can shed light on the structure of the central pattern generator (CPG) for locomotion. We have concentrated attention on the cutaneous reflex pathways that project to the flexor digitorum longus (FDL) motor pool because of that muscle's unique variable behavior during normal and fictive locomotion in the cat. Differential locomotor control of last-order excitatory interneurons in pathways from low-threshold cutaneous afferents in the superficial peroneal and medial plantar afferents to FDL motoneurons is fully documented for the first time. The qualitative patterns of differential control are shown to remain the same whether the FDL muscle is active in early flexion, as usually found, or during the extension phase of fictive locomotion, which is less common during fictive stepping. The patterns of motor pool activity and of reflex pathway modulation indicate that the flexion phase of fictive locomotion has distinct early versus late components. Observations during “normal” and unusual patterns of fictive stepping suggest that some aspects of locomotor pattern formation can be separated from rhythm generation, implying that these two CPG functions may be embodied, at least in part, in distinct neural organizations. The results are discussed in relation to a provisional circuit diagram that could explain the experimental findings.
Gaze-Stabilizing Deficits and Latent Nystagmus in Monkeys With Early-Onset Visual Deprivation: Role of the Pretectal NOT
Authors: Mustari Michael J. , Tusa Ronald J. , Burrows Andrew F. , Fuchs Albert F. , Livingston Christine A.
Published: December 2017

We studied the role of the pretectal nucleus of the optic tract (NOT) in the development of monocular optokinetic nystagmus (OKN) asymmetries and latent nystagmus (LN) in two monkeys reared with binocular deprivation (BD) caused by binocular eyelid suture for either the first 25 or 55 days of life. Single-unit recordings were performed in the right and left NOT of both monkeys at 2–3 yr of age and compared with similar unit recordings in normally reared monkeys. We also examined ocular motor behavior during electrical stimulation of the NOT and during pharmacological inactivation and activation using GABAAagonists and antagonists. In BD animals a large proportion of NOT units was dominated by the contralateral eye, in striking contrast to normal animals where 100% of NOT units were sensitive to stimuli delivered to either eye. In the 55-day BD animal no binocularly sensitive neurons were found, while in the 25-day BD animal 60% of NOT units retained at least some binocular sensitivity. Differences in direction sensitivity were also observed in BD animals. We found that 56% of units in the 55-day BD monkey and 10% of units in the 25-day BD monkey responded preferentially to contraversive visual motion. In contrast, only 5% of the NOT units encountered in normally reared monkeys respond preferentially during contraversive visual motion, the rest were most sensitive to ipsiversive visual motion. NOT neurons of BD monkeys showed a wide range of speed sensitivities similar to that of normal monkeys. Unilateral electrical stimulation of the NOT in BD animals induced a conjugate nystagmus with slow phases directed toward the side of stimulation. When we blocked the activity of NOT units with muscimol, a potent GABAAagonist, LN was abolished. In contrast, LN was increased when spontaneous activity of the NOT was enhanced with bicuculline, a GABAAantagonist. Our results indicate that the NOT in BD monkeys plays an important role in the OKN deficits and LN generation during monocular viewing. We hypothesize that the large proportion of units dominated by the contralateral eye contribute to the development of monocular OKN asymmetries and LN.
Ionic Mechanisms Underlying Burst Firing of Layer III Sensorimotor Cortical Neurons of the Cat: An In Vitro Slice Study
Authors: Nishimura Yoshihiro , Asahi Masaru , Saitoh Koichi , Kitagawa Hirofumi , Kumazawa Yuichi , Itoh Kunio , Lin Min , Akamine Takanobu , Shibuya Hiroshi , Asahara Toshihiro , Yamamoto Tetsuro
Published: December 2017

We examined the ionic mechanisms underlying burst firing in layer III neurons from cat sensorimotor cortex by intracellular recording in a brain slice. Regular spiking was observed in 77.4% of 137 neurons in response to constant intracellular current pulses of 0.5- to 1-s duration. The rest of the neurons showed burst firing. An initial burst followed by regular-spike firing was seen in 71.0% of 31 bursting neurons. The rest of the bursting neurons ( n = 9) exhibited repetitive bursting. In the bursting neurons, spikes comprising the burst were triggered from the afterdepolarization (ADP) of the first spike of the burst. We examined the ionic mechanisms underlying the ADP by applying channel-blocking agents. The ADP was enhanced (rather than blocked) by Ca2+ channel blockade. This enhancement of the ADP by Ca2+channel blockade was apparent even after blockade of the afterhyperpolarization by apamin or intracellular Ca2+ chelation by EGTA. The firing rate of the regular-spiking cells was increased by apamin, intracellular EGTA or Ca2+ channel blockers. In 17.9% of the neurons examined ( n = 56), these agents switched the regular-spiking pattern into a bursting one. Burst firing could not be changed to regular spiking by these agents. Four neurons that responded with a single initial burst in control solution responded with repetitive bursting after application of these agents. We conclude that the main function of Ca2+ influx in layer III neurons is to activate Ca2+-dependent K+ conductance, which prevents or limits burst firing. At a time when spike amplitude was unchanged, the ADP was blocked and the burst firing changed to regular spiking by extracellularly applied tetrodotoxin (TTX) or intracellularly applied N-(2,6-dimethylphenylcarbamoylmethyl) triethyl ammonium bromide (QX314). We concluded that a TTX- and QX314-sensitive Na+ current underlies the ADP and therefore contributes to the burst firing of layer III neurons from the cat cortex.
Sex-Related Differences in Human Pain and Rat Afferent Discharge Evoked by Injection of Glutamate Into the Masseter Muscle
Authors: Cairns Brian E. , Hu James W. , Arendt-Nielsen Lars , Sessle Barry J. , Svensson Peter
Published: December 2017

Animal studies have suggested that tissue injury–related increased levels of glutamate may be involved in peripheral nociceptive mechanisms in deep craniofacial tissues. Indeed, injection of glutamate (0.1–1 M, 10 μl) into the temporomandibular region evokes reflex jaw muscle responses through activation of peripheral excitatory amino acid receptors. It has recently been found that this glutamate-evoked reflex muscle activity is significantly greater in female than male rats. However, it is not known whether peripheral administration of glutamate, in the same concentrations that evoke jaw muscle activity in rats, causes pain in humans or activates deep craniofacial nociceptive afferents. Therefore we examined whether injection of glutamate into the masseter muscle induces pain in male and female volunteers and, since masseter afferent recordings were not feasible in humans, whether glutamate excites putative nociceptive afferents supplying the masseter muscle of male and female rats. Injection of glutamate (0.5 M or 1.0 M, 0.2 ml) into the masseter muscle of both men and women caused significantly higher levels of peak pain, duration of pain, and overall pain than injection of isotonic saline (0.2 ml). In addition, glutamate-evoked peak and overall muscle pain in women was significantly greater than in men. In rats of both sexes, glutamate (10 μl, 0.5 M) evoked activity in a subpopulation of masseter muscle afferents ( n = 36) that projected to the subnucleus caudalis, an important relay of noxious input from the craniofacial region. The largest responses to glutamate were recorded in muscle afferents with the slowest conduction velocities (2.5–5 m/s). Further, glutamate-evoked masseter muscle afferent activity was significantly greater in female than in male rats. These results indicate that glutamate injection into the masseter muscle evokes pain responses that are greater in women than men and that one possible mechanism for this difference may be a greater sensitivity to glutamate of masseter muscle afferents in females. These sex-related differences in acute experimental masseter muscle pain are particularly interesting given the higher prevalence of many chronic muscle pain conditions in women.
Effect of Acute Exposure to Ammonia on Glutamate Transport in Glial Cells Isolated From the Salamander Retina
Authors: Mort Dominic , Marcaggi Païkan , Grant James , Attwell David
Published: December 2017

A rise of brain ammonia level, as occurs in liver failure, initially increases glutamate accumulation in neurons and glial cells. We investigated the effect of acute exposure to ammonia on glutamate transporter currents in whole cell clamped glial cells from the salamander retina. Ammonia potentiated the current evoked by a saturating concentration ofl-glutamate, and decreased the apparent affinity of the transporter for glutamate. The potentiation had a Michaelis-Menten dependence on ammonia concentration, with a K m of 1.4 mM and a maximum potentiation of 31%. Ammonia also potentiated the transporter current produced by d-aspartate. Potentiation of the glutamate transport current was seen even with glutamine synthetase inhibited, so ammonia does not act by speeding glutamine synthesis, contrary to a suggestion in the literature. The potentiation was unchanged in the absence of Cl− ions, showing that it is not an effect on the anion current gated by the glutamate transporter. Ammonium ions were unable to substitute for Na+in driving glutamate transport. Although they can partially substitute for K+ at the cation counter-transport site of the transporter, their occupancy of these sites would produce a potentiation of <1%. Ammonium, and the weak bases methylamine and trimethylamine, increased the intracellular pH by similar amounts, and intracellular alkalinization is known to increase glutamate uptake. Methylamine and trimethylamine potentiated the uptake current by the amount expected from the known pH dependence of uptake, but ammonia gave a potentiation that was larger than could be explained by the pH change, and some potentiation of uptake by ammonia was still seen when the internal pH was 8.8, at which pH further alkalinization does not increase uptake. These data suggest that ammonia speeds glutamate uptake both by increasing cytoplasmic pH and by a separate effect on the glutamate transporter. Approximately two-thirds of the speeding is due to the pH change.
Ef-Current Contributes to Whole-Cell Calcium Current in Low Calcium in Frog Sympathetic Neurons
Authors: Liang Haoya , Elmslie Keith S.
Published: December 2017

Because Ca2+ plays diverse roles in intracellular signaling in neurons, several types of calcium channels are employed to control Ca2+ influx in these cells. Our experiments focus on resolving the paradox of why whole-cell current has not been observed under typical recording conditions for one type of calcium channel that is highly expressed in frog sympathetic neurons. These channels, referred to as Ef-channels, are present in the membrane at a density greater than the channels that carry ∼90% of whole-cell current in low Ba2+; but, Ef-current has not been detected in low Ba2+. Using Ca2+ instead of Ba2+ as the charge carrier, we recorded a possible E-type current in frog sympathetic neurons. The current was resistant to specific blockers of N-, L-, and P/Q-type calcium channels but was more sensitive to Ni2+ block than was N- or L-current. Current amplitude in Ca2+ is slightly greater than that in Ba2+. In 3 mM Ca2+, the current contributed ∼12% of total current at peak voltage and increased at voltages more hyperpolarized to the peak, reaching ∼40% at −30 mV, where whole-cell current starts to activate. The presence of Ef-current in 3 mM Ca2+ suggests a potential role for Ef-channels in regulating calcium influx into sympathetic neurons.
NMDA Antagonists in the Superior Colliculus Prevent Developmental Plasticity But Not Visual Transmission or Map Compression
Authors: Huang L. , Pallas S. L.
Published: December 2017

Partial ablation of the superior colliculus (SC) at birth in hamsters compresses the retinocollicular map, increasing the amount of visual field represented at each SC location. Receptive field sizes of single SC neurons are maintained, however, preserving receptive field properties in the prelesion condition. The mechanism that allows single SC neurons to restrict the number of convergent retinal inputs and thus compensate for induced brain damage is unknown. In this study, we examined the role of N-methyl-d-aspartate (NMDA) receptors in controlling retinocollicular convergence. We found that chronic 2-amino-5-phosphonovaleric acid (APV) blockade of NMDA receptors from birth in normal hamsters resulted in enlarged single-unit receptive fields in SC neurons from normal maps and further enlargement in lesioned animals with compressed maps. The effect was linearly related to lesion size. These results suggest that NMDA receptors are necessary to control afferent/target convergence in the normal SC and to compensate for excess retinal afferents in lesioned animals. Despite the alteration in receptive field size in the APV-treated animals, a complete visual map was present in both normal and lesioned hamsters. Visual responsiveness in the treated SC was normal; thus the loss of compensatory plasticity was not due to reduced visual responsiveness. Our results argue that NMDA receptors are essential for map refinement, construction of receptive fields, and compensation for damage but not overall map compression. The results are consistent with a role for the NMDA receptor as a coincidence detector with a threshold, providing visual neurons with the ability to calculate the amount of visual space represented by competing retinal inputs through the absolute amount of coincidence in their firing patterns. This mechanism of population matching is likely to be of general importance during nervous system development.
Development of Electrophysiological and Morphological Diversity in Autonomic Neurons
Authors: Anderson Rebecca L. , Jobling Phillip , Gibbins Ian L.
Published: December 2017

The generation of neuronal diversity requires the coordinated development of differential patterns of ion channel expression along with characteristic differences in dendritic geometry, but the relations between these phenotypic features are not well known. We have used a combination of intracellular recordings, morphological analysis of dye-filled neurons, and stereological analysis of immunohistochemically labeled sections to investigate the development of characteristic electrical and morphological properties of functionally distinct populations of sympathetic neurons that project from the celiac ganglion to the splanchnic vasculature or the gastrointestinal tract of guinea pigs. At early fetal stages, neurons were significantly more depolarized at rest compared with neurons at later stages, and they generally fired only a single action potential. By mid fetal stages, rapidly and slowly adapting neurons could be distinguished with a topographic distribution matching that found in adult ganglia. Most rapidly adapting neurons (phasic neurons) at this age had a long afterhyperpolarization (LAH) characteristic of mature vasomotor neurons and were preferentially located in the lateral poles of the ganglion, where most neurons contained neuropeptide Y. Most early and mid fetal neurons showed a weak M current, which was later expressed only by rapidly-adapting and LAH neurons. Two different A currents were present in a subset of early fetal neurons and may indicate neurons destined to develop a slowly adapting phenotype (tonic neurons). The size of neuronal cell bodies increased at a similar rate throughout development regardless of their electrical or neurochemical phenotype or their topographical location. In contrast, the rate of dendritic growth of neurons in medial regions of the ganglion was significantly higher than that of neurons in lateral regions. The apparent cell capacitance was highly correlated with the surface area of the soma but not the dendritic tree of the developing neurons. These results demonstrate that the well-defined functional populations of neurons in the celiac ganglion develop their characteristic electrophysiological and morphological properties during early fetal stages of development. This is after the neuronal populations can be recognized by their neurochemical and topographical characteristics but long before the neurons have finished growing. Our data provide strong circumstantial evidence that the development of the full phenotype of different functional classes of autonomic final motor neurons is a multi-step process likely to involve a regulated sequence of trophic interactions.
PP1 Inhibitors DepolarizeHermissendaPhotoreceptors and Reduce K+Currents
Authors: Huang Haojiang , Farley Joseph
Published: December 2017

Previous research indicates that activation of protein kinase C (PKC) plays a critical role in the induction and maintenance of memory-related changes in neural excitability of Type B photoreceptors in the eyes of nudibranch mollusk Hermissenda crassicornis (H.c.). The enhanced excitability of B cells is due in part to PKC-mediated reduction in somatic K+currents. Here we examined the effects of protein phosphatase inhibitors on Type B photoreceptor excitability and K+currents to determine the role(s) of protein phosphatases on memory formation in Hermissenda. Using electrophysiological and pharmacological methods, we found that the PP1 inhibitors calyculin A and inhibitor-2 depolarized Type B photoreceptors by 20–30 mV. A broad-spectrum kinase inhibitor, H7, blocked this effect. The depolarization induced by PP1 inhibition occluded that produced by an in vitro associative conditioning procedure. Calyculin and inhibitor-2 reduced the same B cell K+currents ( IAand Idelayed) that are reduced by in vitro and behavioral conditioning. H7 blocked the reductions. Cantharidic acid (PP2A inhibitor) and cyclosporin (PP2B inhibitor) had negligible effects on B cell resting membrane potential, K+currents, and in vitro conditioning-produced cumulative depolarization of B cells. These results suggest that the functional activity of K+channels in B cells is sustained by basal activity of PP1. Inhibiting PP1 appears to allow one or more constitutively active kinase(s) to reduce K+channel activity and thus mimic the effects of conditioning. Our results suggest that PP1 may oppose and/or constrain the extent of learning-produced changes in B cell excitability.