bluuebunny/crossref_metadata_2025 huggingface dataset:
Detection of Vibration Transmitted Through an Object Grasped in the Hand
Authors: Brisben A. J. , Hsiao S. S. , Johnson K. O.
Published: December 2017

Detection of vibration transmitted through an object grasped in the hand. A tool or probe often functions as an extension of the hand, transmitting vibrations to the hand to produce a percept of the object contacting the tool or probe. This paper reports the psychophysical results of a combined psychophysical and neurophysiological study of the perception of vibration transmitted through a cylinder grasped in the hand. In the first part of the psychophysical study, 19 subjects grasped a cylinder, 32 mm diam, with an embedded motor that caused vibration parallel to the axis of the cylinder. The relationship between threshold and frequency was the traditional U-shaped function with a minimum between 150 and 200 Hz. Except a study by Békésy in which subjects grasped a rod that vibrated parallel to the skin surface, thresholds above 20 Hz were lower and the slopes were steeper than any reported previously. Thresholds were <0.01 μm in some subjects. Data from both the psychophysical and the neurophysiological studies suggest that detection performance at frequencies >20 Hz was based on activity in Pacinian afferents. The extreme sensitivity compared with previous reports may have resulted from differences in contact area, direction of vibration, contact force, and the shape of the stimulus probe. The effects of each of these variables were studied. At 40 and 300 Hz (frequencies near the lower and upper end of the Pacinian range) thresholds were 9.8 and 18.5 dB (68 and 88%) lower, respectively, when subjects grasped the cylinder than when a 1-mm-diam probe vibrated perpendicular to the skin. These differences were accounted for as follows: 1) thresholds at a single fingerpad obtained with the large cylindrical surface were, on average, 20 and 60% lower, respectively, than thresholds with the punctate probe; 2) thresholds at the palm were, on average, 15 and 40% lower, respectively, than at the fingerpads; 3) thresholds obtained when the subjects grasped the cylinder averaged 40 and 20% less, respectively, than when the cylinder contacted only the palm; 4) thresholds with the cylinder contacting two fingers were 10 and 30% lower, respectively, than thresholds with the cylinder contacting a single finger; and 5) thresholds with vibration parallel to the skin surface were, on average, 10 and 30% lower, respectively, than thresholds with vibration perpendicular to the skin. Contact force, which was varied from 0.05 to 1.0 N, had no effect.
Inhibitory Control of LTP and LTD: Stability of Synapse Strength
Authors: Steele Philip M. , Mauk Michael D.
Published: December 2017

Inhibitory control of LTP and LTD: stability of synapse strength. Although much is known about the induction of synaptic plasticity, the persistence of memories suggests the importance of understanding factors that maintain synaptic strength and prevent unwanted synaptic changes. Here we present evidence that recurrent inhibitory connections in the CA1 region of hippocampus may contribute to this task by modulating the relative ability to induce long-term potentiation and depression (LTP and LTD). Bath application of the γ-aminobutyric acid (GABA) type A agonist muscimol to hippocampal slices increased the range of frequencies that produce LTD, whereas in the presence of the GABA type A antagonist picrotoxin LTD was induced only at very low stimulation frequencies (0.25–0.5 Hz). Because one source of GABAergic input to CA1 pyramidal cells is via recurrent inhibition, we tested the prediction that elevated postsynaptic spike activity would increase feedback GABA inhibition and favor the induction of LTD. By using an induction stimulation of 8 Hz, which alone produced no net change in synaptic strength, we found that stimulation presented during antidromic activation of pyramidal cell spikes induced LTD. This effect was blocked by picrotoxin. The influence of recurrent inhibition on LTP and LTD displays properties that may decrease the potential for self-reinforcing, runaway changes in synapse strength. A mechanism of this sort may help maintain patterns of synaptic strengths despite the ongoing opportunities for plasticity produced by synapse activation.
Functional GABAAReceptor Heterogeneity of Acutely Dissociated Hippocampal CA1 Pyramidal Cells
Authors: Tietz Elizabeth I. , Kapur Jaideep , Macdonald Robert L.
Published: December 2017

Functional GABAAreceptor heterogeneity of acutely dissociated hippocampal CA1 pyramidal cells. CA1 pyramidal cells were voltage clamped, and GABA was applied to individual cells with a modified U-tube, rapid drug application system. With Vh= −50 mV, inward currents elicited by 10 μM GABA were inhibited by GABAAreceptor (GABAR) antagonists and were baclofen insensitive, suggesting that GABA actions on isolated CA1 pyramidal cells were GABAR mediated. GABA concentration-response curves averaged from all cells were fitted best with a two-site equation, indicating the presence of at least two GABA binding sites, a higher-affinity site (EC50–1= 11.0 μM) and a lower-affinity site (EC50–2= 334.2 μM), on two or more populations of cells. The effects of GABAR allosteric modulators on peak concentration-dependent GABAR currents were complex and included monophasic (loreclezole) or multiphasic (diazepam) enhancement, mixed enhancement/inhibition (DMCM, zolpidem) or multiphasic inhibition (zinc). Monophasic (70% of cells) or biphasic (30% of cells) enhancement of GABAR currents by diazepam suggested three different sites on GABARs (EC50–1=1.8 nM; EC50–2= 75.8 nM; EC50–3= 275.9 nM) revealing GABAR heterogeneity. The imidazopyridine zolpidem enhanced GABAR currents in 70% of cells with an EC50= 222.5 nM, suggesting a predominance of moderate affinity α2 (or α3-) subtype-containing BZ Type IIA receptors. A small fraction of cells (10%) had a high affinity for zolpidem, something that is suggestive of α1 subtype-containing BZ Type I receptors. The remaining 30% of cells were insensitive to or inhibited by zolpidem, suggesting the presence of α5 subtype-containing BZ Type IIB receptors. Whether BZ Type I and Type II receptors coexist could not be determined. The β-carboline methyl 6,7-dimethoxy-4-ethyl-β-carboline-3-carboxylate (DMCM) inhibited GABAR currents in all cells at midnanomolar concentrations, but in addition, potentiated GABAR currents in some cells at low nanomolar concentrations, characterizing two groups of cells, the latter likely due to functional assembly of α5βxγ2GABARs. In all cells, GABAR currents were moderately sensitive (EC50= 9 μM) to loreclezole, consistent with a relatively greater β3 subtype, than β1 subtype, subunit mRNA expression. Two populations of cells were identified based on their sensitivities to zinc(IC50= 28 and 182 μM), suggesting the presence of at least two GABAR isoforms including α5β3γ2 GABARs. Consistent with the heterogeneity of expression of GABAR subunit mRNA and protein in the hippocampus and based on their differential responses to GABA and to allosteric modulators, distinct populations of CA1 pyramidal cells likely express multiple, functional GABAR isoforms.
Ultrastructural Analysis of Ectopic Synaptic Boutons Arising From Peripherally Regenerated Primary Afferent Fibers
Authors: Koerber H. Richard , Mirnics Karoly , Kavookjian Anahid M. , Light Alan R.
Published: December 2017

Ultrastructural analysis of ectopic synaptic boutons arising from peripherally regenerated primary afferent fibers. The central axons of peripherally regenerated Aβ primary sensory neurons were impaled in the dorsal columns of α-chloralose-anesthetized cats 9–12 mo after axotomy. The adequate peripheral stimulus was determined, and the afferent fibers intracellularly stimulated while simultaneously recording the resulting cord dorsum potentials (CDPs). Fibers that successfully had reinnervated the skin responded to light tactile stimulation, and evoked CDPs that suggested dorsally located boutons were stained intracellularly with horseradish peroxidase (HRP). Two HRP-stained regenerated Aβ afferent fibers were recovered that supported large numbers of axon collaterals and swellings in laminae I, IIo, and IIi. Sections containing the ectopic collateral fibers and terminals in the superficial dorsal horn were embedded in plastic. Analyses of serial ultrathin sections revealed that ectopic projections from both regenerated fibers supported numerous synaptic boutons filled with clear round vesicles, a few large dense core vesicles (LDCVs) and several mitochondria (>3). All profiles examined in serial sections (19) formed one to three asymmetric axo-dendritic contacts. Unmyelinated portions of ectopic fibers giving rise to en passant and terminal boutons often contained numerous clear round vesicles. Several boutons (47%) received asymmetric contacts from axon terminals containing pleomorphic vesicles. These results strongly suggest that regenerated Aβ fibers activated by light tactile stimuli support functional connections in the superficial dorsal horn that have distinct ultrastructural features. In addition, the appearance of LDCVs suggests that primary sensory neurons are capable of changing their neurochemical phenotype.
Long-Term Potentiation in the Dentate Gyrus Is Not Linked to Increased Extracellular Glutamate Concentration
Authors: Jay T. M. , Zilkha E. , Obrenovitch T. P.
Published: December 2017

Long-term potentiation in the dentate gyrus is not linked to increased extracellular glutamate concentration. Long-term potentiation (LTP) of excitatory transmission is a likely candidate for the encoding and storage of information in the mammalian brain. There is a general agreement that LTP involves an increase in synaptic strength, but the mechanisms underlying this persistent change are unclear and controversial. Synaptic efficacy may be enhanced because more transmitter glutamate is released or because postsynaptic responsiveness increases or both. The purpose of this study was to examine whether increased extracellular glutamate concentration was associated with the robust and well-characterized LTP that can be induced in the rat dentate gyrus. To favor the detection of any putative change in extracellular glutamate associated with LTP, our experimental strategy included the following features. 1) Two separate series of experiments were carried out with animals under pentobarbital or urethan anesthesia; 2) changes in extracellular concentration of glutamate were monitored continuously by microdialysis coupled to enzyme amperometry; and 3) dialysate glutamate levels and changes in the slope of excitatory postsynaptic potential evoked by activation of the perforant path were recorded precisely at the same site. Tetanic stimulation of the perforant path increased persistently test-evoked responses in the dentate gyrus (by 19 and 14% in barbiturate and urethan group, respectively), but there was no glutamate change either during or after LTP induction and no indication of increased glutamate efflux when low-frequency stimulation was applied. The results do not rule out a possible contribution of enhanced glutamate exocytosis to LTP induction and/or maintenance because such a presynaptic change may not be detectable extracellularly. However, our findings and other data supporting the notion that neurotransmitter glutamate may hardly leak out of the synaptic cleft conflict with the hypothesis that LTP could also involve a broad synaptic spillover of glutamate.
I A in Kenyon Cells of the Mushroom Body of Honeybees Resembles Shaker Currents: Kinetics, Modulation by K+, and Simulation
Authors: Pelz Corinna , Jander Johannes , Rosenboom Hendrik , Hammer Martin , Menzel Randolf
Published: December 2017

I A in Kenyon cells of the mushroom body of honeybees resembles shaker currents: kinetics, modulation by K+, and simulation. Cultured Kenyon cells from the mushroom body of the honeybee, Apis mellifera, show a voltage-gated, fast transient K+ current that is sensitive to 4-aminopyridine, an A current. The kinetic properties of this A current and its modulation by extracellular K+ ions were investigated in vitro with the whole cell patch-clamp technique. The A current was isolated from other voltage-gated currents either pharmacologically or with suitable voltage-clamp protocols. Hodgkin- and Huxley-style mathematical equations were used for the description of this current and for the simulation of action potentials in a Kenyon cell model. Activation and inactivation of the A current are fast and voltage dependent with time constants of 0.4 ± 0.1 ms (means ± SE) at +45 mV and 3.0 ± 1.6 ms at +45 mV, respectively. The pronounced voltage dependence of the inactivation kinetics indicates that at least a part of this current of the honeybee Kenyon cells is a shaker-like current. Deactivation and recovery from inactivation also show voltage dependency. The time constant of deactivation has a value of 0.4 ± 0.1 ms at −75 mV. Recovery from inactivation needs a double-exponential function to be fitted adequately; the resulting time constants are 18 ± 3.1 ms for the fast and 745 ± 107 ms for the slow process at −75 mV. Half-maximal activation of the A current occurs at −0.7 ± 2.9 mV, and half-maximal inactivation occurs at −54.7 ± 2.4 mV. An increase in the extracellular K+concentration increases the conductance and accelerates the recovery from inactivation of the A current, affecting the slow but not the fast time constant. With respect to these modulations the current under investigation resembles some of the shaker-like currents. The data of the A current were incorporated into a reduced computational model of the voltage-gated currents of Kenyon cells. In addition, the model contained a delayed rectifier K+ current, a Na+current, and a leakage current. The model is able to generate an action potential on current injection. The model predicts that the A current causes repolarization of the action potential but not a delay in the initiation of the action potential. It further predicts that the activation of the delayed rectifier K+ current is too slow to contribute markedly to repolarization during a single action potential. Because of its fast activation, the A current reduces the amplitude of the net depolarizing current and thus reduces the peak amplitude and the duration of the action potential.
Three-Dimensional Eye-Head Coordination During Gaze Saccades in the Primate
Authors: Crawford J. Douglas , Ceylan Melike Z. , Klier Eliana M. , Guitton Daniel
Published: December 2017

Three-dimensional eye-head coordination during gaze saccades in the primate. The purpose of this investigation was to describe the neural constraints on three-dimensional (3-D) orientations of the eye in space (Es), head in space (Hs), and eye in head (Eh) during visual fixations in the monkey and the control strategies used to implement these constraints during head-free gaze saccades. Dual scleral search coil signals were used to compute 3-D orientation quaternions, two-dimensional (2-D) direction vectors, and 3-D angular velocity vectors for both the eye and head in three monkeys during the following visual tasks: radial to/from center, repetitive horizontal, nonrepetitive oblique, random (wide 2-D range), and random with pin-hole goggles. Although 2-D gaze direction (of Es) was controlled more tightly than the contributing 2-D Hs and Eh components, the torsional standard deviation of Es was greater (mean 3.55°) than Hs (3.10°), which in turn was greater than Eh (1.87°) during random fixations. Thus the 3-D Es range appeared to be the byproduct of Hs and Eh constraints, resulting in a pseudoplanar Es range that was twisted (in orthogonal coordinates) like the zero torsion range of Fick coordinates. The Hs fixation range was similarly Fick-like, whereas the Eh fixation range was quasiplanar. The latter Eh range was maintained through exquisite saccade/slow phase coordination, i.e., during each head movement, multiple anticipatory saccades drove the eye torsionally out of the planar range such that subsequent slow phases drove the eye back toward the fixation range. The Fick-like Hs constraint was maintained by the following strategies: first, during purely vertical/horizontal movements, the head rotated about constantly oriented axes that closely resembled physical Fick gimbals, i.e., about head-fixed horizontal axes and space-fixed vertical axes, respectively (although in 1 animal, the latter constraint was relaxed during repetitive horizontal movements, allowing for trajectory optimization). However, during large oblique movements, head orientation made transient but dramatic departures from the zero-torsion Fick surface, taking the shortest path between two torsionally eccentric fixation points on the surface. Moreover, in the pin-hole goggle task, the head-orientation range flattened significantly, suggesting a task-dependent default strategy similar to Listing’s law. These and previous observations suggest two quasi-independent brain stem circuits: an oculomotor 2-D to 3-D transformation that coordinates anticipatory saccades with slow phases to uphold Listing’s law, and a flexible “Fick operator” that selects head motor error; both nested within a dynamic gaze feedback loop.
Effect of Spatial Attention on the Responses of Area MT Neurons
Authors: Seidemann Eyal , Newsome William T.
Published: December 2017

Effect of spatial attention on the responses of area MT neurons. This study examines the influence of spatial attention on the responses of neurons in the middle temporal visual area (MT or V5) of extrastriate cortex. Two monkeys were trained to perform a direction-discrimination task. On each trial, two apertures of random-dot stimuli appeared simultaneously at two spatially separated locations; the monkeys were required to discriminate the direction of stimulus motion at one location while ignoring the stimulus at the other location. After extensive training, we recorded the responses of MT neurons in two configurations: 1) Both apertures placed “within” the neuron’s receptive field (RF) and 2) one aperture covering the RF while the other was presented at a “remote” location. For each unit we compared the responses to identical stimulus displays when the monkey was instructed to attend to one or the other aperture. The responses of MT neurons were 8.7% stronger, on average, when the monkey attended to the spatial location that contained motion in the “preferred” direction. Attentional effects were equal, on average, in the within RF and remote configurations. The attentional modulations began ∼300 ms after stimulus onset, gradually increased throughout the trial, and peaked near stimulus offset. An analysis of the neuronal responses on error trials suggests that the monkeys failed to attend to the appropriate spatial location on these trials. The relatively weak attentional effects that we observed contrast strikingly with recent results of Treue and Maunsell, who demonstrated very strong attentional modulations (median effect >80%) in MT in a task that shares many features with ours. Our results suggest that spatial attention alone is not sufficient to induce strong attentional effects in MT even when two competing motion stimuli appear within the RF of the recorded neuron. The difference between our results and those of Treue and Maunsell suggests that the magnitude of the attentional effects in MT may depend critically on how attention is directed to a particular stimulus and on the precise demands of the task.
Effect of Reversible Inactivation of Macaque Lateral Intraparietal Area on Visual and Memory Saccades
Authors: Li Chiang-Shan Ray , Mazzoni Pietro , Andersen Richard A.
Published: December 2017

Effect of reversible inactivation of macaque lateral intraparietal area on visual and memory saccades. Previous studies from our laboratory identified a parietal eye field in the primate lateral intraparietal sulcus, the lateral intraparietal area (area LIP). Here we further explore the role of area LIP in processing saccadic eye movements by observing the effects of reversible inactivation of this area. One to 2 μl of muscimol (8 mg/ml) were injected at locations where saccade-related activities were recorded for each lesion experiment. After the muscimol injection we observed in two macaque monkeys consistent effects on both the metrics and dynamics of saccadic eye movements at many injection sites. These effects usually took place within 10–30 min and disappeared after 5–6 h in most cases and certainly when tested the next day. After muscimol injection memory saccades directed toward the contralesional and upper space became hypometric, and in one monkey those to the ipsilesional space were slightly but significantly hypermetric. In some cases, the scatter of the end points of memory saccades was also increased. On the other hand, the metrics of visual saccades remained relatively intact. Latency for both visual and memory saccades toward the contralesional space was increased and in many cases displayed a higher variance after muscimol lesion. At many injection sites we also observed an increase of latency for visual and memory saccades toward the upper space. The peak velocities for memory saccades toward the contralesional space were decreased after muscimol injection. The peak velocities of visual saccades were not significantly different from those of the controls. The duration of saccadic eye movements either to the ipsilesional or contralesional space remained relatively the same for both visual and memory saccades. Overall these results demonstrated that we were able to selectively inactivate area LIP and observe effects on saccadic eye movements. Together with our previous recording studies these results futher support the view that area LIP plays a direct role in processing incoming sensory information to program saccadic eye movements. The results are consistent with our unit recording data and microstimulation studies, which suggest that area LIP represents contralateral space and also has a bias for the upper visual field.
Modulation of N-Type Ca2+Channels by Intracellular pH in Chick Sensory Neurons
Authors: Kiss Laszlo , Korn Stephen J.
Published: December 2017

Modulation of N-type Ca2+channels by intracellular pH in chick sensory neurons. Both physiological and pathological neuronal events, many of which elevate intracellular [Ca2+], can produce changes in intracellular pH of between 0.15 and 0.5 U, between pH 7.4 and 6.8. N-type Ca2+channels, which are intimately involved in exocytosis and other excitable cell processes, are sensitive to intracellular pH changes. However, the pH range over which N-type Ca2+channels are sensitive, and the sensitivity of N-type Ca2+channels to small changes in intracellular pH, are unknown. We studied the influence of intracellular pH changes on N-type calcium channel currents in dorsal root ganglion neurons, acutely isolated from 14-day-old chick embryos. Intracellular pH was monitored in patch-clamp recordings with the fluorescent dye, BCECF, and manipulated in both the acidic and basic direction by extracellular application of NH4+in the presence and absence of intracellular NH4+. Changes in intracellular pH between 6.6 and 7.5 produced a graded change in Ca2+current magnitude with no apparent shift in activation potential. Intracellular acidification from pH 7.3 to 7.0 reversibly inhibited Ca2+currents by 40%. Acidification from pH 7.3 to pH 6.6 reversibly inhibited Ca2+currents by 65%. Alkalinization from pH 7.3 to 7.5 potentiated Ca2+currents by approximately 40%. Channels were sensitive to pHichanges with high intracellular concentrations of the Ca2+chelator, bis-( o-aminophenoxy)- N,N,N′,N′-tetraacetic acid, which indicates that the effects of pHidid not involve a Ca2+-dependent mechanism. These data indicate that N-type Ca2+channel currents are extremely sensitive to small changes in pHiin the range produced by both physiological and pathological events. Furthermore, these data suggest that modulation of N-type Ca2+channels by pHimay play an important role in physiological processes that produce small changes in pHiand a protective role in pathological mechanisms that produce larger changes in pHi.
Role of Proprioceptive Signals From an Insect Femur-Tibia Joint in Patterning Motoneuronal Activity of an Adjacent Leg Joint
Authors: Hess Dietmar , Büschges Ansgar
Published: December 2017

Role of proprioceptive signals from an insect femur-tibia joint in patterning motoneuronal activity of an adjacent leg joint. Interjoint reflex function of the insect leg contributes to postural control at rest or to movement control during locomotor movements. In the stick insect ( Carausius morosus), we investigated the role that sensory signals from the femoral chordotonal organ (fCO), the transducer of the femur-tibia (FT) joint, play in patterning motoneuronal activity in the adjacent coxa-trochanteral (CT) joint when the joint control networks are in the movement control mode of the active behavioral state. In the active behavioral state, sensory signals from the fCO induced transitions of activity between antagonistic motoneuron pools, i.e., the levator trochanteris and the depressor trochanteris motoneurons. As such, elongation of the fCO, signaling flexion of the FT joint, terminated depressor motoneuron activity and initiated activity in levator motoneurons. Relaxation of the fCO, signaling extension of the FT joint, induced the opposite transition by initiating depressor motoneuron activity and terminating levator motoneuron activity. This interjoint influence of sensory signals from the fCO was independent of the generation of the intrajoint reflex reversal in the FT joint, i.e., the “active reaction,” which is released by elongation signals from the fCO. The generation of these transitions in activity of trochanteral motoneurons barely depended on position or velocity signals from the fCO. This contrasts with the situation in the resting behavioral state when interjoint reflex action markedly depends on actual fCO stimulus parameters, i.e., position and velocity signals. In the active behavioral state, movement signals from the fCO obviously trigger or release centrally generated transitions in motoneuron activity, e.g., by affecting central rhythm generating networks driving trochanteral motoneuron pools. This conclusion was tested by stimulating the fCO in “fictive rhythmic” preparations, activated by the muscarinic agonist pilocarpine in the otherwise isolated and deafferented mesothoracic ganglion. In this situation, sensory signals from the fCO did in fact reset and entrain rhythmic activity in trochanteral motoneurons. The results indicate for the first time that when the stick insect locomotor system is active, sensory signals from the proprioceptor of one leg joint, i.e., the fCO, pattern motor activity in an adjacent leg joint, i.e., the CT joint, by affecting the central rhythm generating network driving the motoneurons of the adjacent joint.
Membrane Dysfunction Induced by In Vitro Ischemia in Rat Hippocampal CA1 Pyramidal Neurons
Authors: Tanaka E. , Yamamoto S. , Inokuchi H. , Isagai T. , Higashi H.
Published: December 2017

Membrane dysfunction induced by in vitro ischemia in rat hippocampal CA1 pyramidal neurons. Intracellular and single-electrode voltage-clamp recordings were made to investigate the process of membrane dysfunction induced by superfusion with oxygen and glucose-deprived (ischemia-simulating) medium in hippocampal CA1 pyramidal neurons of rat tissue slices. To assess correlation between potential change and membrane dysfunction, the recorded neurons were stained intracellularly with biocytin. A rapid depolarization was produced ∼6 min after starting superfusion with ischemia-simulating medium. When oxygen and glucose were reintroduced to the bathing medium immediately after generating the rapid depolarization, the membrane did not repolarize but depolarized further, the potential reaching 0 mV ∼5 min after the reintroduction. In single-electrode voltage-clamp recording, a corresponding rapid inward current was observed when the membrane potential was held at −70 mV. After the reintroduction of oxygen and glucose, the current induced by ischemia-simulating medium partially returned to preexposure levels. These results suggest that the membrane depolarization is involved with the membrane dysfunction. The morphological aspects of biocytin-stained neurons during ischemic exposure were not significantly different from control neurons before the rapid depolarization. On the other hand, small blebs were observed on the surface of the neuron within 0.5 min of generating the rapid depolarization, and blebs increased in size after 1 min. After 3 min, neurons became larger and swollen. The long and transverse axes and area of the cross-sectional cell body were increased significantly 1 and 3 min after the rapid depolarization. When Ca2+-free (0 mM) with Co2+ (2.5 mM)-containing medium including oxygen and glucose was applied within 1 min after the rapid depolarization, the membrane potential was restored completely to the preexposure level in the majority of neurons. In these neurons, the long axis was lengthened without any blebs being apparent on the membrane surface. These results suggest that the membrane dysfunction induced by in vitro ischemia may be due to a Ca2+-dependent process that commences ∼1.5 min after and is completed 3 min after the onset of the rapid depolarization. Because small blebs occurred immediately after the rapid depolarization and large blebs appeared 1.5–3 min after, it is likely that the transformation from small to large blebs may result in the observed irreversible membrane dysfunction.
Identification of the Cerebral Loci Processing Human Swallowing With H2 15O PET Activation
Authors: Hamdy Shaheen , Rothwell John C. , Brooks David J. , Bailey Dale , Aziz Qasim , Thompson David G.
Published: December 2017

Identification of the cerebral loci processing human swallowing with H2 15O PET activation. Lesional and electrophysiological data implicate a role for the cerebral cortex in the initiation and modulation of human swallowing, and yet its functional neuroanatomy remains undefined. We therefore conducted a functional study of the cerebral loci processing human volitional swallowing with 15O-labeled water positron emission tomography (PET) activation imaging. Regional cerebral activation was investigated in 8 healthy right handed male volunteers with a randomized 12-scan paradigm of rest and water swallows (5 ml/bolus, continuous infusion) at increasing frequencies of 0.1, 0.2, and 0.3 Hz, which were visually cued and monitored with submental electromyogram (EMG). Group and individual linear covariate analyses were performed with SPM96. In five of eight subjects, the cortical motor representation of pharynx was subsequently mapped with transcranial magnetic stimulation (TMS) in a posthoc manner to substantiate findings of hemispheric differences in sensorimotor cortex activation seen with PET. During swallowing, group PET analysis identified increased regional cerebral blood flow (rCBF) ( P < 0.001) within bilateral caudolateral sensorimotor cortex [Brodmann’s area (BA) 3, 4, and 6], right anterior insula (BA 16), right orbitofrontal and temporopolar cortex (BA 11 and 38), left mesial premotor cortex (BA 6 and 24), left temporopolar cortex and amygdala (BA 38 and 34), left superiomedial cerebellum, and dorsal brain stem. Decreased rCBF ( P < 0.001) was also observed within bilateral posterior parietal cortex (BA 7), right anterior occipital cortex (BA 19), left superior frontal cortex (BA 8), right prefrontal cortex (BA 9), and bilateral superiomedial temporal cortex (BA 41 and 42). Individual PET analysis revealed asymmetric representation within sensorimotor cortex in six of eight subjects, four lateralizing to right hemisphere and two to left hemisphere. TMS mapping in the five subjects identified condordant interhemisphere asymmetries in the motor representation for pharynx, consistent with the PET findings. We conclude that volitional swallowing recruits multiple cerebral regions, in particular sensorimotor cortex, insula, temporopolar cortex, cerebellum, and brain stem, the sensorimotor cortex displaying strong degrees of interhemispheric asymmetry, further substantiated with TMS. Such findings may help explain the variable nature of swallowing disorders after stroke and other focal lesions to the cerebral cortex.
Reacquisition Deficits in Prism Adaptation After Muscimol Microinjection Into the Ventral Premotor Cortex of Monkeys
Authors: Kurata Kiyoshi , Hoshi Eiji
Published: December 2017

Reacquisition deficits in prism adaptation after muscimol microinjection into the ventral premotor cortex of monkeys. A small amount of muscimol (1 μl; concentration, 5 μg/μl) was injected into the ventral and dorsal premotor cortex areas (PMv and PMd, respectively) of monkeys, which then were required to perform a visually guided reaching task. For the task, the monkeys were required to reach for a target soon after it was presented on a screen. While performing the task, the monkeys’ eyes were covered with left 10°, right 10°, or no wedge prisms, for a block of 50–100 trials. Without the prisms, the monkeys reached the targets accurately. When the prisms were placed, the monkeys initially misreached the targets because the prisms displaced the visual field. Before the muscimol injection, the monkeys adapted to the prisms in 10–20 trials, judging from the horizontal distance between the target location and the point where the monkey touched the screen. After muscimol injection into the PMv, the monkeys lost the ability to readapt and touched the screen closer to the location of the targets as seen through the prisms. This deficit was observed at selective target locations, only when the targets were shifted contralaterally to the injected hemisphere. When muscimol was injected into the PMd, no such deficits were observed. There were no changes in the reaction and movement times induced by muscimol injections in either area. The results suggest that the PMv plays an important role in motor learning, specifically in recalibrating visual and motor coordinates.
Developmental Aspects and Mechanisms of Rat Caudal Hypothalamic Neuronal Responses to Hypoxia
Authors: Horn Eric M. , Dillon Glenn H. , Fan Yi-Ping , Waldrop Tony G.
Published: December 2017

Developmental aspects and mechanisms of rat caudal hypothalamic neuronal responses to hypoxia. Previous reports from this laboratory have shown that a high percentage of neurons in the caudal hypothalamus are stimulated by hypoxia both in vivo and in vitro. This stimulation is in the form of an increase in firing frequency and significant membrane depolarization. The goal of the present study was to determine if this hypoxia-induced excitation is influenced by development. In addition, we sought to determine the mechanism by which hypoxia stimulates caudal hypothalamic neurons. Caudal hypothalamic neurons from neonatal (4–16 days) or juvenile (20–40 days) rats were patch-clamped, and the whole cell voltage and current responses to moderate (10% O2) or severe (0% O2) hypoxia were recorded in the brain slice preparation. Analysis of tissue oxygen levels demonstrated no significant difference in the levels of tissue oxygen in brain slices between the different age groups. A significantly larger input resistance, time constant and half-time to spike height was observed for neonatal neurons compared with juvenile neurons. Both moderate and severe hypoxia elicited a net inward current in a significantly larger percentage of caudal hypothalamic neurons from rats aged 20–40 days (juvenile) as compared with rats aged 4–16 days (neonatal). In contrast, there was no difference in the magnitude of the inward current response to moderate or severe hypoxia between the two age groups. Those cells that were stimulated by hypoxia demonstrated a significant decrease in input resistance during hypoxic stimulation that was not observed in those cells unaffected by hypoxia. A subset of neurons were tested independent of age for the ability to maintain the inward current response to hypoxia during synaptic blockade (11.4 mM Mg2+/0.2 mM Ca2+). Most of the neurons tested (88.9%) maintained a hypoxic excitation during synaptic blockade, and this inward current response was unaffected by addition of 2 mM cobalt chloride to the bathing medium. In contrast, perfusion with the Na+ channel blocker, tetrodotoxin (1–2 μM) or Na+ replacement with N-methyl-d-glucamine (NMDG) significantly reduced the inward current response to hypoxia. Furthermore, the input resistance decrease observed during hypoxia was attenuated significantly during perfusion with NMDG. These results indicate the excitation elicited by hypoxia in hypothalamic neurons is age dependent. In addition, the inward current response of caudal hypothalamic neurons is not dependent on synaptic input but results from a sodium-dependent conductance.
Anatomic, Intrinsic, and Synaptic Properties of Dorsal and Ventral Division Neurons in Rat Medial Geniculate Body
Authors: Bartlett Edward L. , Smith Philip H.
Published: December 2017

Anatomic, intrinsic, and synaptic properties of dorsal and ventral division neurons in rat medial geniculate body. Presently little is known about what basic synaptic and cellular mechanisms are employed by thalamocortical neurons in the two main divisions of the auditory thalamus to elicit their distinct responses to sound. Using intracellular recording and labeling methods, we characterized anatomic features, membrane properties, and synaptic inputs of thalamocortical neurons in the dorsal (MGD) and ventral (MGV) divisions in brain slices of rat medial geniculate body. Quantitative analysis of dendritic morphology demonstrated that tufted neurons in both divisions had shorter dendrites, smaller dendritic tree areas, more profuse branching, and a greater dendritic polarization compared with stellate neurons, which were only found in MGD. Tufted neuron dendritic polarization was not as strong or consistent as earlier Golgi studies suggested. MGV and MGD cells had similar intrinsic properties except for an increased prevalence of a depolarizing sag potential in MGV neurons. The sag was the only intrinsic property correlated with cell morphology, seen only in tufted neurons in either division. Many MGV and MGD neurons received excitatory and inhibitory inferior colliculus (IC) inputs (designated IN/EX or EX/IN depending on excitation/inhibition sequence). However, a significant number only received excitatory inputs (EX/O) and a few only inhibitory (IN/O). Both MGV and MGD cells displayed similar proportions of response combinations, but suprathreshold EX/O responses only were observed in tufted neurons. Excitatory and inhibitory postsynaptic potentials (EPSPs and IPSPs) had multiple distinguishable amplitude levels implying convergence. Excitatory inputs activated α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and N-methyl-d-aspartate (NMDA) receptors the relative contributions of which were variable. For IN/EX cells with suprathreshold inputs, first-spike timing was independent of membrane potential unlike that of EX/O cells. Stimulation of corticothalamic (CT) and thalamic reticular nucleus (TRN) axons evoked a GABAA IPSP, EPSP, GABAB IPSP sequence in most neurons with both morphologies in both divisions. TRN IPSPs and CT EPSPs were graded in amplitude, again suggesting convergence. CT inputs activated AMPA and NMDA receptors. The NMDA component of both IC and CT inputs had an unusual voltage dependence with a detectable dl-2-amino-5-phosphonovaleric acid-sensitive component even below −70 mV. First-spike latencies of CT evoked action potentials were sensitive to membrane potential regardless of whether the TRN IPSP was present. Overall, our in vitro data indicate that reported regional differences in the in vivo responses of MGV and MGD cells to auditory stimuli are not well correlated with major differences in intrinsic membrane features or synaptic responses between cell types.
Rhythmicity in Single Fiber Postganglionic Activity Supplying the Rat Tail
Authors: Häbler H.-J. , Bartsch T. , Jänig W.
Published: December 2017

Rhythmicity in single fiber postganglionic activity supplying the rat tail. The temporal pattern of ongoing sympathetic vasoconstrictor activity may play an important role for neurovascular transmission. Here we analyzed the activity of postganglionic fibers projecting into the ventral collector nerve of anesthetized and artificially ventilated vagotomized Wistar rats with respect to the presence of rhythmic firing under normocapnic conditions. Most of the fibers studied were likely vasoconstrictor and involved in thermoregulation. Accumulated histograms of sympathetic activity were produced synchronized with the electrocardiogram to detect cardiac rhythmicity, with phrenic nerve activity to detect modulation with the central respiratory cycle, and with tracheal pressure to uncover a reflex modulation associated with artificial ventilation. Sympathetic activity, phrenic activity, and tracheal pressure also were examined by spectral analysis and autocorrelation to detect rhythmicities distinct from respiration. Twenty-seven filaments containing two to seven fibers with spontaneous activity and 51 single fibers were analyzed. Ongoing activity was 1.12 ± 0.65 imp/s (mean ± SD, n = 51); conduction velocity was 0.62 ± 0.06 m/s ( n = 30). Cardiac rhythmicity in sympathetic activity was weak (46.2 ± 16.4%). The dominant rhythm in the activity of 19/27 few-fiber preparations and 37/51 single fibers corresponded to the central respiratory cycle. The pattern consisted of an inhibition during inspiration and an activation in expiration. In 10/19 few-fiber preparations and 21/37 single fibers of this group, there was also a concomitant, less prominent rhythm related to artificial ventilation. By contrast, 8/27 few-fiber preparations and 11/51 single fibers exhibited a dominant pump-related modulation, whereas phrenic-related rhythmicity was subordinate. The dominant rhythm in the activity of two single fibers was related to neither central respiration nor artificial ventilation. We conclude that the ongoing activity of most postganglionic neurons supplying the rat tail is modulated by the central respiratory rhythm generator, suggesting that changes in respiratory drive may alter perfusion of the tail and therefore heat dissipation. Reflex modulation in parallel with artificial ventilation, independent of vagal afferents and possibly due to ventilatory changes of baroreceptor activity, is also an important source of rhythmicity in these neurons.
Sensitivity to Simulated Directional Sound Motion in the Rat Primary Auditory Cortex
Authors: Doan Daryl E. , Saunders James C.
Published: December 2017

Sensitivity to simulated directional sound motion in the rat primary auditory cortex. This paper examines neuron responses in rat primary auditory cortex (AI) during sound stimulation of the two ears designed to simulate sound motion in the horizontal plane. The simulated sound motion was synthesized from mathematical equations that generated dynamic changes in interaural phase, intensity, and Doppler shifts at the two ears. The simulated sounds were based on moving sources in the right frontal horizontal quadrant. Stimuli consisted of three circumferential segments between 0 and 30°, 30 and 60°, and 60 and 90° and four radial segments at 0, 30, 60, and 90°. The constant velocity portion of each segment was 0.84 m long. The circumferential segments and center of the radial segments were calculated to simulate a distance of 2 m from the head. Each segment had two trajectories that simulated motion in both directions, and each trajectory was presented at two velocities. Young adult rats were anesthetized, the left primary auditory cortex was exposed, and microelectrode recordings were obtained from sound responsive cells in AI. All testing took place at a tonal frequency that most closely approximated the best frequency of the unit at a level 20 dB above the tuning curve threshold. The results were presented on polar plots that emphasized the two directions of simulated motion for each segment rather than the location of sound in space. The trajectory exhibiting a “maximum motion response” could be identified from these plots. “Neuron discharge profiles” within these trajectories were used to demonstrate neuron activity for the two motion directions. Cells were identified that clearly responded to simulated uni- or multidirectional sound motion (39%), that were sensitive to sound location only (19%), or that were sound driven but insensitive to our location or sound motion stimuli (42%). The results demonstrated the capacity of neurons in rat auditory cortex to selectively process dynamic stimulus conditions representing simulated motion on the horizontal plane. Our data further show that some cells were responsive to location along the horizontal plane but not sensitive to motion. Cells sensitive to motion, however, also responded best to the moving sound at a particular location within the trajectory. It would seem that the mechanisms underlying sensitivity to sound location as well as direction of motion converge on the same cell.
Glutamate Controls the Induction of GABA-Mediated Giant Depolarizing Potentials Through AMPA Receptors in Neonatal Rat Hippocampal Slices
Authors: Bolea Sonia , Avignone Elena , Berretta Nicola , Sanchez-Andres Juan V. , Cherubini Enrico
Published: December 2017

Glutamate controls the induction of GABA-mediated giant depolarizing potentials through AMPA receptors in neonatal rat hippocampal slices. Giant depolarizing potentials (GDPs) are generated by the interplay of the depolarizing action of GABA and glutamate. In this study, single and dual whole cell recordings (in current-clamp configuration) were performed from CA3 pyramidal cells in hippocampal slices obtained from postnatal (P) days P1- to P6-old rats to evaluate the role of ionotropic glutamate receptors in GDP generation. Superfusion of 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) (10–40 μM) completely blocked GDPs. However, in the presence of CNQX, it was still possible to re-induce the appearance of GDPs with GABA (20 μM) or (RS)-α-amino-3-hydroxy-5-methyl-4-isoxadepropionate (AMPA) (5 μM). This effect was prevented by the more potent and selective AMPA receptor antagonist GYKI 53655 (50–100 μM). In the presence of GYKI 53655, both kainic or domoic acid (0.1–1 μM) were unable to induce GDPs. In contrast, bath application of d-(−)-2-amino-5-phosphonopentanoic acid (50 μM) or (+)-3-(2carboxy-piperazin-4-yl)-propyl-l-phosphonic acid (20 μM) produced only a 37 ± 9% (SE) and 36 ± 11% reduction in GDPs frequency, respectively. Cyclothiazide, a selective blocker of AMPA receptor desensitization, increased GDP frequency by 76 ± 14%. Experiments were also performed with an intracellular solution containing KF to block GABAAreceptor-mediated responses. In these conditions, a glutamatergic component of GDP was revealed. GDPs could still be recorded synchronous with those detected simultaneously with KCl-filled electrodes, although their amplitude was smaller. Similar results were found in pair recordings obtained from minislices containing only a small portion of the CA3 area. These data suggest that GDP generation requires activation of AMPA receptors by local release of glutamate from recurrent collaterals.