bluuebunny/crossref_metadata_2025 huggingface dataset:
Optical Imaging of Odor Preference Memory in the Rat Olfactory Bulb
Authors: Yuan Qi , Harley Carolyn W. , McLean John H. , Knöpfel Thomas
Published: December 2017

Early olfactory preference learning in rat pups occurs when novel odors are paired with reinforcing tactile stimulation that activate the noradrenergic locus coeruleus. Pairing of odor and a noradrenergic agonist in the olfactory bulb is both necessary and sufficient for odor preference learning. This suggests the memory change occurs in the olfactory bulb. Previous electrophysiological experiments demonstrated that odor preference training induces an increase in the field excitatory postsynaptic potential to olfactory nerve input and an alteration, after training, in glomerular [14C]2- deoxyglucose uptake and in single-unit responses of principal cells. We investigate here whether, 24 h after olfactory preference training, there is an alteration in intrinsic optical signals at the glomerular level. Six-day-old rat pups were trained, as previously, for a peppermint odor preference. Trained pups and control littermates were subjected to imaging of odor-induced intrinsic optical signals 1 day after the training session. Trained pups exhibited significantly larger responses to the peppermint compared with untrained littermates previously exposed to the same odor. The response of trained pups to a control odor (amyl acetate) was, however, not significantly different from that of untrained littermates. These observations demonstrate that odor preference memory can be read-out by optical imaging techniques.
Ca2+Clearance at Growth Cones Produced by Crayfish Motor Axons in an Explant Culture
Authors: Rumpal Nidhi , Lnenicka Gregory A.
Published: December 2017

Intracellular free Ca2+concentration ([Ca2+]i) plays an important role in the regulation of growth cone (GC) motility; however, the mechanisms responsible for clearing Ca2+from GCs have not been examined. We studied the Ca2+-clearance mechanisms in GCs produced by crayfish tonic and phasic motor axons by measuring the decay of [Ca2+]iafter a high [K+] depolarizing pulse using fura-2AM. Tonic motor axons regenerating in explant cultures develop GCs with more rapid Ca2+clearance than GCs from phasic axons. When Na/Ca exchange was blocked by replacing external Na+with N-methyl-d-glucamine (NMG), [Ca2+]idecay was delayed in both tonic and phasic GCs. Tonic GCs appear to have higher Na/Ca exchange activity than phasic ones since reversal of Na/Ca exchange by lowering external Na+caused a greater increase in [Ca2+]ifor tonic than phasic GCs. Application of the mitochondrial inhibitors, Antimycin A1 (1 μM) and CCCP (10 μM), demonstrated that mitochondrial Ca2+uptake/release was more prominent in phasic than tonic GCs. When both Na/Ca exchange and mitochondria were inhibited, the plasma membrane Ca2+ATPase was effective in extruding Ca2+from tonic, but not phasic GCs. We conclude that Na/Ca exchange plays a prominent role in extruding large Ca2+loads from both tonic and phasic GCs. High Na/Ca exchange activity in tonic GCs contributes to the rapid decay of [Ca2+]iin these GCs; low rates of Ca2+extrusion plus the release of Ca2+from mitochondria prolongs the decay of [Ca2+]iin the phasic GCs.
Color Processing in Macaque Striate Cortex: Electrophysiological Properties
Authors: Landisman Carole E. , Ts'O Daniel Y.
Published: December 2017

We have shown in the accompanying paper that optical imaging of macaque striate cortex reveals patches that are preferentially activated by equiluminant chromatic gratings compared with luminance gratings. These imaged color patches are highly correlated, although not always in one-to-one correspondence, with the cytochrome-oxidase (CO) blobs. In the present study, we have investigated the electrophysiological properties of neurons in the imaged color patches and the CO blobs. Our results indicate that individual blobs tend to contain cells of only one type of color opponency: either red/green or blue/yellow. Individual imaged color patches, however, can bridge blobs of similar opponency or differing opponency. When imaged color patches contain two blobs of differing opponency, the cells in the bridge region exhibit mixed color properties that are not opponent along the two cardinal color axes (either red/green or blue/yellow). Two blobs within a single imaged color patch receive input from the same eye or from different eyes. In the latter case, the bridge region between blobs contains binocular cells that are color selective. Because the cells recorded in imaged color patches were more color selective and unoriented than cells outside of color patches, color properties appear to be organized in a clustered and segregated fashion in primate V1.
Interaction Between Disinhibited Bursting and Fictive Locomotor Patterns in the Rat Isolated Spinal Cord
Authors: Beato M. , Nistri A.
Published: December 2017

Using a transverse barrier that allowed discrete application of neurochemicals to certain lumbar regions of the rat isolated spinal cord, we studied the intersegmental organization of rhythmic patterns recorded extracellularly from ventral roots and intracellularly from single motoneurons. Fictive locomotor patterns were elicited by serotonin (5-HT) and/or N-methyl-d-aspartate (NMDA) or high K+ solution applied to the rostral or caudal lumbar region of the cord. Neither 4-aminopyridine nor Mg2+-free solution shared this property. Coapplication of strychnine and bicuculline (blockers of fast synaptic inhibition) to the caudal part elicited slow bursting in the whole cord. These bursts could trigger episodes of fictive locomotion patterns in the rostral roots. When the rostral region was exposed to 5-HT and/or NMDA (during continuous application of strychnine and bicuculline caudally) a standard locomotor-like pattern was generated during each interburst interval and was surprisingly expressed with its typical pattern alternation even in the caudal area despite the local presence of strychnine and bicuculline. Midsagittal splitting of the caudal region did not change this alternating pattern, indicating that it was driven by rostral regions above the surgical cut. Discrete changes in the concentrations of NMDA rostrally modulated the burst amplitude recorded in the same region after caudal application of strychnine and bicuculline. The period of fictive locomotor patterns changed bimodally depending on the temporal relation with disinhibited bursts, indicating a tight interaction between these two rhythmic activities. These results are interpreted on the basis of a model that assumes a modular arrangement for the locomotor central pattern generator, made up by a series of unit burst generators with serial and crossed connections.
Properties of Delay-Period Neuronal Activity in the Monkey Dorsolateral Prefrontal Cortex During a Spatial Delayed Matching-to-Sample Task
Authors: Sawaguchi Toshiyuki , Yamane Itaru
Published: December 2017

The dorsolateral prefrontal cortex (PFC) has been implicated in visuospatial memory, and its cellular basis has been extensively studied with the delayed-response paradigm in monkeys. However, using this paradigm, it is difficult to dissociate neuronal activities related to visuospatial memory from those related to motor preparation, and few studies have provided evidence for the involvement of PFC neurons in visuospatial memory of a sensory cue, rather than in motor preparation. To extend this finding, we examined neuronal activities in the dorsolateral PFC while a rhesus monkey performed a spatial delayed matching-to-sample (SDMTS) task, which allows us to adequately access visuospatial memory independent of any sensorimotor components. The SDMTS task required the subject to make a lever-holding NOGO response or a lever-releasing GO response when a visuospatial matching cue (white spot, one of four peripheral locations, 15° in eccentricity) matched or did not match a sample cue (physically the same as the matching cue) that had been presented prior to a delay period (3 s). Thus, the SDMTS task requires the subject to remember visuospatial information regarding the sample cue location during the delay period and is suitable for accessing visuospatial memory independent of any sensorimotor components, such as motor preparation, for directed movements. Of a total of 385 task-related neurons, 184 showed a sustained increase in activity during the delay period (“delay-period activity”). Most of these neurons (n = 165/184, 90%) showed positional delay-period activity, i.e., delay-period activity where the magnitude differed significantly with the position of the sample cue. This activity appears to be involved in visuospatial memory and to form a “memory field.” To quantitatively examine the properties of positional delay-period activity, we introduced a tuning index (TI) and a discriminative index (DI), which represent the sharpness of tuning and the discriminative ability, respectively, of positional delay-period activity. Both TI and DI varied among neurons with positional delay-period activity and were closely related to the time from the onset of the sample cue to the onset of positional delay-period activity; positional delay-period activity with sharper tuning and a greater discriminative ability had a slower onset. Furthermore, at the population level, both TI and DI were increased during the delay period in the neuronal population with a high DI value. These results extend previous findings to suggest that integrative, convergent processes of neuronal activities for increasing the accuracy of visuospatial memory may occur in the dorsolateral PFC. Thus, a critical role of the dorsolateral PFC in visuospatial memory may be to sharpen it to guide behaviors/decisions requiring accurate visuospatial memory.
Effects of Aging on Motor-Unit Control Properties
Authors: Erim Zeynep , Beg M. Faisal , Burke David T. , de Luca Carlo J.
Published: December 2017

It was hypothesized that the age-related alterations in the morphological properties of a motor unit would be accompanied by modifications in the control aspects of the motor unit, as either an adaptive or compensatory mechanism to preserve smooth force production. In specific, the objective of the study was to investigate the age-related alterations in the concurrent firing behavior of multiple motor units in the first dorsal interosseous (FDI) muscle in isometric contractions at 20 and 50% of the subject's voluntary contraction level. Analysis of the data collected from 10 young (24–37 yr of age) and 10 elderly (65–88 yr of age) subjects led to three novel observations regarding the firing behavior of aged motor units. 1) Among elderly subjects, there is a decrease in the common fluctuations that are observed among the firing rates of motor units in the young. 2) The relationship observed between the firing rate and recruitment threshold of young subjects is disturbed in the elderly. Although in young subjects, at any point in a given submaximal contraction, earlier recruited motor units have higher firing rates than later-recruited units; in aged subjects this dependency of firing rate on recruitment rank is compromised. 3) The progressive decrease observed in the firing rates of concurrently active motor units in constant-force contractions in the young is not seen in the aged. In addition to these original findings, this study provided support for earlier reports of 1) decreased average firing rates probably reflecting the slowing of the muscle, 2) a shift in recruitment thresholds toward lower force levels in line with the shift toward type I fibers, and 3) multiphasic action potential shapes indicative of the reinnervation process that takes place during aging. Taken as a whole, these findings indicate significant age-related modifications in the control properties of human motor units.
Responses of Medullary Dorsal Horn Neurons to Corneal Stimulation by CO2 Pulses in the Rat
Authors: Hirata Harumitsu , Hu James W. , Bereiter David A.
Published: December 2017

Corneal-responsive neurons were recorded extracellularly in two regions of the spinal trigeminal nucleus, subnucleus interpolaris/caudalis (Vi/Vc) and subnucleus caudalis/upper cervical cord (Vc/C1) transition regions, from methohexital-anesthetized male rats. Thirty-nine Vi/Vc and 26 Vc/C1 neurons that responded to mechanical and electrical stimulation of the cornea were examined for convergent cutaneous receptive fields, responses to natural stimulation of the corneal surface by CO2 pulses (0, 30, 60, 80, and 95%), effects of morphine, and projections to the contralateral thalamus. Forty-six percent of mechanically sensitive Vi/Vc neurons and 58% of Vc/C1 neurons were excited by CO2 stimulation. The evoked activity of most cells occurred at 60% CO2 after a delay of 7–22 s. At the Vi/Vc transition three response patterns were seen. Type I cells ( n = 11) displayed an increase in activity with increasing CO2 concentration. Type II cells ( n = 7) displayed a biphasic response, an initial inhibition followed by excitation in which the magnitude of the excitatory phase was dependent on CO2 concentration. A third category of Vi/Vc cells (type III, n = 3) responded to CO2 pulses only after morphine administration (>1.0 mg/kg). At the Vc/C1 transition, all CO2-responsive cells ( n = 15) displayed an increase in firing rates with greater CO2 concentration, similar to the pattern of type I Vi/Vc cells. Comparisons of the effects of CO2 pulses on Vi/Vc type I units, Vi/Vc type II units, and Vc/C1 corneal units revealed no significant differences in threshold intensity, stimulus encoding, or latency to sustained firing. Morphine (0.5–3.5 mg/kg iv) enhanced the CO2-evoked activity of 50% of Vi/Vc neurons tested, whereas all Vc/C1 cells were inhibited in a dose-dependent, naloxone-reversible manner. Stimulation of the contralateral posterior thalamic nucleus antidromically activated 37% of Vc/C1 corneal units; however, no effective sites were found within the ventral posteromedial thalamic nucleus or nucleus submedius. None of the Vi/Vc corneal units tested were antidromically activated from sites within these thalamic regions. Corneal-responsive neurons in the Vi/Vc and Vc/C1 regions likely serve different functions in ocular nociception, a conclusion reflected more by the difference in sensitivity to analgesic drugs and efferent projection targets than by the CO2 stimulus intensity encoding functions. Collectively, the properties of Vc/C1 corneal neurons were consistent with a role in the sensory-discriminative aspects of ocular pain due to chemical irritation. The unique and heterogeneous properties of Vi/Vc corneal neurons suggested involvement in more specialized ocular functions such as reflex control of tear formation or eye blinks or recruitment of antinociceptive control pathways.
Cerebellar Subjects Show Impaired Adaptation of Anticipatory EMG During Catching
Authors: Lang Catherine E. , Bastian Amy J.
Published: December 2017

We evaluated the role of the cerebellum in adapting anticipatory muscle activity during a multijointed catching task. Individuals with and without cerebellar damage caught a series of balls of different weights dropped from above. In Experiment 1(light-heavy-light), each subject was required to catch light balls ( baseline phase), heavy balls ( adaptation phase), and then light balls again ( postadaptation phase). Subjects were not told when the balls would be switched, and they were required to keep their hand within a vertical spatial “window” during the catch. During the series of trials, we measured three-dimensional (3-D) position and electromyogram (EMG) from the catching arm. We modeled the adaptation process using an exponential decay function; this model allowed us to dissociate adaptation from performance variability. Results from the position data show that cerebellar subjects did not adapt or adapted very slowly to the changed ball weight when compared with the control subjects. The cerebellar group required an average of 30.9 ± 8.7 trials (mean ± SE) to progress approximately two-thirds of the way through the adaptation compared with 1.7 ± 0.2 trials for the control group. Only control subjects showed a negative aftereffect indicating storage of the adaptation. No difference in performance variability existed between the two groups. EMG data show that control subjects increased their anticipatory muscle activity in the flexor muscles of the arm to control the momentum of the ball at impact. Cerebellar subjects were unable to differentially increase the anticipatory muscle activity across three joints to perform the task successfully. In Experiment 2 (heavy-light-heavy), we tested to see whether the rate of adaptation changed when adapting to a light ball versus a heavy ball. Subjects caught the heavy balls (baseline phase), the light balls (adaptation phase), and then heavy balls again (postadaptation phase). Comparison of rates of adaptation between Experiment 1 and Experiment 2showed that the rate of adaptation was unchanged whether adapting to a light ball or a heavy ball. Given these findings, we conclude that the cerebellum is important in generating the appropriate anticipatory muscle activity across multiple muscles and modifying it in response to changing demands though trial-and-error practice.
Two Components of Transducer Adaptation in Auditory Hair Cells
Authors: Wu Yuh-Cherng , Ricci A. J. , Fettiplace R.
Published: December 2017

Mechanoelectrical transducer currents in turtle auditory hair cells adapted to maintained stimuli via a Ca2+-dependent mechanism characterized by two time constants of ∼1 and 15 ms. The time course of adaptation slowed as the stimulus intensity was raised because of an increased prominence of the second component. The fast component of adaptation had a similar time constant for both positive and negative displacements and was unaffected by the myosin ATPase inhibitors, vanadate and butanedione monoxime. Adaptation was modeled by a scheme in which Ca2+ions, entering through open transducer channels, bind at two intracellular sites to trigger independent processes leading to channel closure. It was assumed that the second site activates a modulator with 10-fold slower kinetics than the first site. The model was implemented by computing Ca2+diffusion within a single stereocilium, incorporating intracellular calcium buffers and extrusion via a plasma membrane CaATPase. The theoretical results reproduced several features of the experimental responses, including sensitivity to the concentration of external Ca2+and intracellular calcium buffer and a dependence on the onset speed of the stimulus. The model also generated damped oscillatory transducer responses at a frequency dependent on the rate constant for the fast adaptive process. The properties of fast adaptation make it unlikely to be mediated by a myosin motor, and we suggest that it may result from Ca2+binding to the transducer channel or a nearby cytoskeletal element.
Temporal Encoding of the Voice Onset Time Phonetic Parameter by Field Potentials Recorded Directly From Human Auditory Cortex
Authors: Steinschneider Mitchell , Volkov Igor O. , Noh M. Daniel , Garell P. Charles , Howard Matthew A.
Published: December 2017

Voice onset time (VOT) is an important parameter of speech that denotes the time interval between consonant onset and the onset of low-frequency periodicity generated by rhythmic vocal cord vibration. Voiced stop consonants (/b/, /g/, and /d/) in syllable initial position are characterized by short VOTs, whereas unvoiced stop consonants (/p/, /k/, and t/) contain prolonged VOTs. As the VOT is increased in incremental steps, perception rapidly changes from a voiced stop consonant to an unvoiced consonant at an interval of 20–40 ms. This abrupt change in consonant identification is an example of categorical speech perception and is a central feature of phonetic discrimination. This study tested the hypothesis that VOT is represented within auditory cortex by transient responses time-locked to consonant and voicing onset. Auditory evoked potentials (AEPs) elicited by stop consonant-vowel (CV) syllables were recorded directly from Heschl's gyrus, the planum temporale, and the superior temporal gyrus in three patients undergoing evaluation for surgical remediation of medically intractable epilepsy. Voiced CV syllables elicited a triphasic sequence of field potentials within Heschl's gyrus. AEPs evoked by unvoiced CV syllables contained additional response components time-locked to voicing onset. Syllables with a VOT of 40, 60, or 80 ms evoked components time-locked to consonant release and voicing onset. In contrast, the syllable with a VOT of 20 ms evoked a markedly diminished response to voicing onset and elicited an AEP very similar in morphology to that evoked by the syllable with a 0-ms VOT. Similar response features were observed in the AEPs evoked by click trains. In this case, there was a marked decrease in amplitude of the transient response to the second click in trains with interpulse intervals of 20–25 ms. Speech-evoked AEPs recorded from the posterior superior temporal gyrus lateral to Heschl's gyrus displayed comparable response features, whereas field potentials recorded from three locations in the planum temporale did not contain components time-locked to voicing onset. This study demonstrates that VOT at least partially is represented in primary and specific secondary auditory cortical fields by synchronized activity time-locked to consonant release and voicing onset. Furthermore, AEPs exhibit features that may facilitate categorical perception of stop consonants, and these response patterns appear to be based on temporal processing limitations within auditory cortex. Demonstrations of similar speech-evoked response patterns in animals support a role for these experimental models in clarifying selected features of speech encoding.
Function of Specific K+ Channels in Sustained High-Frequency Firing of Fast-Spiking Neocortical Interneurons
Authors: Erisir A. , Lau D. , Rudy B. , Leonard C. S.
Published: December 2017

Fast-spiking GABAergic interneurons of the neocortex and hippocampus fire high-frequency trains of brief action potentials with little spike-frequency adaptation. How these striking properties arise is unclear, although recent evidence suggests K+ channels containing Kv3.1-Kv3.2 proteins play an important role. We investigated the role of these channels in the firing properties of fast-spiking neocortical interneurons from mouse somatosensory cortex using a pharmacological and modeling approach. Low tetraethylammonium (TEA) concentrations (≤1 mM), which block only a few known K+channels including Kv3.1-Kv3.2, profoundly impaired action potential repolarization and high-frequency firing. Analysis of the spike trains evoked by steady depolarization revealed that, although TEA had little effect on the initial firing rate, it strongly reduced firing frequency later in the trains. These effects appeared to be specific to Kv3.1 and Kv3.2 channels, because blockade of dendrotoxin-sensitive Kv1 channels and BK Ca2+-activated K+ channels, which also have high TEA sensitivity, produced opposite or no effects. Voltage-clamp experiments confirmed the presence of a Kv3.1-Kv3.2–like current in fast-spiking neurons, but not in other interneurons. Analysis of spike shape changes during the spike trains suggested that Na+ channel inactivation plays a significant role in the firing-rate slowdown produced by TEA, a conclusion that was supported by computer simulations. These findings indicate that the unique properties of Kv3.1-Kv3.2 channels enable sustained high-frequency firing by facilitating the recovery of Na+ channel inactivation and by minimizing the duration of the afterhyperpolarization in neocortical interneurons.
Responses to Contour Features in Macaque Area V4
Authors: Pasupathy Anitha , Connor Charles E.
Published: December 2017

The ventral pathway in visual cortex is responsible for the perception of shape. Area V4 is an important intermediate stage in this pathway, and provides the major input to the final stages in inferotemporal cortex. The role of V4 in processing shape information is not yet clear. We studied V4 responses to contour features (angles and curves), which many theorists have proposed as intermediate shape primitives. We used a large parametric set of contour features to test the responses of 152 V4 cells in two awake macaque monkeys. Most cells responded better to contour features than to edges or bars, and about one-third exhibited systematic tuning for contour features. In particular, many cells were selective for contour feature orientation, responding to angles and curves pointing in a particular direction. There was a strong bias toward convex (as opposed to concave) features, implying a neural basis for the well-known perceptual dominance of convexity. Our results suggest that V4 processes information about contour features as a step toward complex shape recognition.
Muscarinic Receptor Activation Induces Depolarizing Plateau Potentials in Bursting Neurons of the Rat Subiculum
Authors: Kawasaki Hiroto , Palmieri Carmela , Avoli Massimo
Published: December 2017

Acetylcholine functions as a neuromodulator in the mammalian brain by binding to specific receptors and thus bringing about profound changes in neuronal excitability. Activation of muscarinic receptors often results in an increased excitability of cortical cells. It is, however, unknown whether such an action is present in the subiculum, a limbic structure that may be involved in cognitive processes as well as in seizure propagation. Most rat subicular neurons are endowed of intrinsic membrane properties that make them fire action potential bursts. Using intracellular recordings from these bursting cells in a slice preparation, we report here that application of the cholinergic agonist carbachol (CCh, 30–100 μM) to medium containing ionotropic excitatory amino acid receptor antagonists reduces burst-afterhyperpolarizations (burst-AHPs) and discloses depolarizing plateau potentials that outlast the triggering current pulses by 140–2,800 ms. These plateau potentials appear with CCh concentrations >50 μM and are dependent on the resting membrane potential and on the intensity/duration of the triggering pulse; are recorded during application of tetrodotoxin (1 μM, n = 5 neurons); but are markedly reduced by replacing 82% of extracellular Na+with equimolar choline ( n = 6). Plateau potentials also are abolished by Co2+ (2 mM; n = 5) or Cd2+ (1 mM; n = 2) application and by recording with electrodes containing the Ca2+chelator bis(2-aminophenoxy)ethane- N, N,N′,N′-tetraacetic acid (0.2 M; n = 6). CCh-induced burst-AHP reduction and plateau potentials are reversed by the muscarinic antagonist atropine (0.5 μM, n = 7). In conclusion, our findings demonstrate a powerful muscarinic modulation of the intrinsic excitability of subicular bursting cells that is predominated by the appearance of plateau potentials. These changes in excitability may contribute to physiological processes such as learning or memory and play a role in the generation of epileptiform depolarizations. We propose that, as in other limbic structures, muscarinic plateau potentials in the subiculum are mainly due to a Ca2+-dependent nonselective cationic conductance.
Quantitative Analysis of Abducens Neuron Discharge Dynamics During Saccadic and Slow Eye Movements
Authors: Sylvestre Pierre A. , Cullen Kathleen E.
Published: December 2017

The mechanics of the eyeball and its surrounding tissues, which together form the oculomotor plant, have been shown to be the same for smooth pursuit and saccadic eye movements. Hence it was postulated that similar signals would be carried by motoneurons during slow and rapid eye movements. In the present study, we directly addressed this proposal by determining which eye movement–based models best describe the discharge dynamics of primate abducens neurons during a variety of eye movement behaviors. We first characterized abducens neuron spike trains, as has been classically done, during fixation and sinusoidal smooth pursuit. We then systematically analyzed the discharge dynamics of abducens neurons during and following saccades, during step-ramp pursuit and during high velocity slow-phase vestibular nystagmus. We found that the commonly utilized first-order description of abducens neuron firing rates (FR = b + kE + rE˙, where FR is firing rate, E and E˙ are eye position and velocity, respectively, and b, k, and r are constants) provided an adequate model of neuronal activity during saccades, smooth pursuit, and slow phase vestibular nystagmus. However, the use of a second-order model, which included an exponentially decaying term or “slide” (FR = b + kE + rE˙ + uË − c[Formula: see text]), notably improved our ability to describe neuronal activity when the eye was moving and also enabled us to model abducens neuron discharges during the postsaccadic interval. We also found that, for a given model, a single set of parameters could not be used to describe neuronal firing rates during both slow and rapid eye movements. Specifically, the eye velocity and position coefficients ( r and k in the above models, respectively) consistently decreased as a function of the mean (and peak) eye velocity that was generated. In contrast, the bias ( b, firing rate when looking straight ahead) invariably increased with eye velocity. Although these trends are likely to reflect, in part, nonlinearities that are intrinsic to the extraocular muscles, we propose that these results can also be explained by considering the time-varying resistance to movement that is generated by the antagonist muscle. We conclude that to create realistic and meaningful models of the neural control of horizontal eye movements, it is essential to consider the activation of the antagonist, as well as agonist motoneuron pools.
Mechanical and Heat Sensitization of Cutaneous Nociceptors After Peripheral Inflammation in The Rat
Authors: Andrew David , Greenspan Joel D.
Published: December 2017

Tissue injuries commonly cause an increase in pain sensitivity, so that normally painful stimuli become more painful (hyperalgesia), and those usually associated with nonnoxious sensations evoke pain (allodynia). The neural bases for these sensory phenomena have been explored most extensively using heat injuries and experimental arthritis as models. Heat sensitization of cutaneous nociceptors is observed after burns, and sensitization of articular afferents to limb movements occurs after knee joint inflammation. These are likely to be peripheral mechanisms of hyperalgesia. Others, using different models of peripheral inflammation, have only rarely found mechanical sensitization of cutaneous nociceptors. In general these studies have failed to evaluate suprathreshold mechanical sensitivity, which has led to the concept of enhanced spinal cord processing (“central sensitization”) serving as the neural substrate for mechanical hyperalgesia. In the current experiments, the mechanical and heat responses of cutaneous nociceptors supplying the glabrous skin of the rat hindpaw were studied 16–24 h after induction of acute inflammation with complete Freund's adjuvant. Single-fiber recordings were made from nociceptors in the sciatic nerve of barbiturate-anesthetized animals, and their responses compared with those obtained from nociceptors tested identically in normal animals. Nociceptors were characterized by the following: 1) graded mechanical stimuli (5–90 g) delivered with probes of tip area of 1 and 0.1 mm2, 2) their adaptive responses to 2-min mechanical stimuli at three intensities, and 3) their responses to graded heat stimuli (40–50°C). Forty-three nociceptors were studied in the inflamed state; 20 were A fibers, and the remainder were C fibers. Mechanical thresholds, determined with calibrated monofilaments, were not significantly different from controls. Sensitization to suprathreshold mechanical stimuli was observed for both A- and C-fiber nociceptors, although it was greater for the A fibers. Similarly, sensitization during testing of adaptive properties of A- and C-fiber nociceptors was seen, although it was limited to the dynamic (initial) and not the static (plateau) phase of the response. Heat sensitization was observed in 25% of A-fiber nociceptors, but the responses of C fibers to heat were depressed. Other indicators of neuronal sensitization, such as spontaneous activity and expanded receptive fields, were also observed. It was concluded that the mechanical hyperalgesia caused by peripheral inflammation could be explained by nociceptor sensitization. Central mechanisms cannot be completely ruled out as contributing to such hyperalgesia, although their role may be much smaller than previously envisaged.
Effects of Feedback Projections From Area 18 Layers 2/3 to Area 17 Layers 2/3 in the Cat Visual Cortex
Authors: Martinez-Conde Susana , Cudeiro Javier , Grieve Kenneth L. , Rodriguez Rosa , Rivadulla Casto , Acuña Carlos
Published: December 2017

In the absence of a direct geniculate input, area 17 cells in the cat are nevertheless able to respond to visual stimuli because of feedback connections from area 18. Anatomic studies have shown that, in the cat visual cortex, layer 5 of area 18 projects to layer 5 of area 17, and layers 2/3 of area 18 project to layers 2/3 of area 17. What is the specific role of these connections? Previous studies have examined the effect of area 18 layer 5 blockade on cells in area 17 layer 5. Here we examine whether the feedback connections from layers 2/3 of area 18 influence the orientation tuning and velocity tuning of cells in layers 2/3 of area 17. Experiments were carried out in anesthetized and paralyzed cats. We blocked reversibly a small region (300 μm radius) in layers 2/3 of area 18 by iontophoretic application of GABA and recorded simultaneously from cells in layers 2/3 of area 17 while stimulating with oriented sweeping bars. Area 17 cells showed either enhanced or suppressed visual responses to sweeping bars of various orientations and velocities during area 18 blockade. For most area 17 cells, orientation bandwidths remained unaltered, and we never observed visual responses during blockade that were absent completely in the preblockade condition. This suggests that area 18 layers 2/3 modulate visual responses in area 17 layers 2/3 without fundamentally altering their specificity.
Motor Cortical Activity During Drawing Movements: Population Representation During Lemniscate Tracing
Authors: Schwartz Andrew B. , Moran Daniel W.
Published: December 2017

Activity was recorded extracellularly from single cells in motor and premotor cortex as monkeys traced figure-eights on a touch-sensitive computer monitor using the index finger. Each unit was recorded individually, and the responses collected from four hemispheres (3 primary motor and 1 dorsal premotor) were analyzed as a population. Population vectors constructed from this activity accurately and isomorphically represented the shape of the drawn figures showing that they represent the spatial aspect of the task well. These observations were extended by examining the temporal relation between this neural representation and finger displacement. Movements generated during this task were made in four kinematic segments. This segmentation was clearly evident in a time series of population vectors. In addition, the [Formula: see text] power law described for human drawing was also evident in the neural correlate of the monkey hand trajectory. Movement direction and speed changed continuously during the task. Within each segment, speed and direction changed reciprocally. The prediction interval between the population vector and movement direction increased in the middle of the segments where curvature was high, but decreased in straight portions at the beginning and end of each segment. In contrast to direction, prediction intervals between the movement speed and population vector length were near-constant with only a modest modulation in each segment. Population vectors predicted direction (vector angle) and speed (vector length) throughout the drawing task. Joint angular velocity and arm muscle EMG were well correlated to hand direction, suggesting that kinematic and kinetic parameters are correlated in these tasks.
Membrane Capacitance of Cortical Neurons and Glia During Sleep Oscillations and Spike-Wave Seizures
Authors: Amzica Florin , Neckelmann Dag
Published: December 2017

Dual intracellular recordings in vivo were used to disclose relationships between cortical neurons and glia during spontaneous slow (<1 Hz) sleep oscillations and spike-wave (SW) seizures in cat. Glial cells displayed a slow membrane potential oscillation (<1 Hz), in close synchrony with cortical neurons. In glia, each cycle of this oscillation was made of a round depolarizing potential of 1.5–3 mV. The depolarizing slope corresponded to a steady depolarization and sustained synaptic activity in neurons (duration, 0.5–0.8 s). The repolarization of the glial membrane (duration, 0.5–0.8 s) coincided with neuronal hyperpolarization, associated with disfacilitation, and suppressed synaptic activity in cortical networks. SW seizures in glial cells displayed phasic events, synchronized with neuronal paroxysmal potentials, superimposed on a plateau of depolarization, that lasted for the duration of the seizure. Measurements of the neuronal membrane capacitance during slow oscillating patterns showed small fluctuations around the resting values in relation to the phases of the slow oscillation. In contrast, the glial capacitance displayed a small-amplitude oscillation of 1–2 Hz, independent of phasic sleep and seizure activity. Additionally, in both cell types, SW seizures were associated with a modulatory, slower oscillation (≈0.2 Hz) and a persistent increase of capacitance, developing in parallel with the progression of the seizure. These capacitance variations were dependent on the severity of the seizure and the distance between the presumed seizure focus and the recording site. We suggest that the capacitance variations may reflect changes in the membrane surface area (swelling) and/or of the interglial communication via gap junctions, which may affect the synchronization and propagation of paroxysmal activities.
Electrophysiological and Morphological Diversity of Mouse Sympathetic Neurons
Authors: Jobling Phillip , Gibbins Ian L.
Published: December 2017

We have used multiple-labeling immunohistochemistry, intracellular dye-filling, and intracellular microelectrode recordings to characterize the morphological and electrical properties of sympathetic neurons in the superior cervical, thoracic, and celiac ganglia of mice. Neurochemical and morphological characteristics of neurons varied between ganglia. Thoracic sympathetic ganglia contained three main populations of neurons based on differential patterns of expression of immunoreactivity to tyrosine hydroxylase, neuropeptide Y (NPY) and vasoactive intestinal peptide (VIP). In the celiac ganglion, nearly all neurons contained immunoreactivity to both tyrosine hydroxylase and NPY. Both the overall size of the dendritic tree and the number of primary dendrites were greater in neurons from the thoracic and celiac ganglia compared with those from the superior cervical ganglion. The electrophysiological properties of sympathetic neurons depended more on their ganglion of origin rather than their probable targets. All neurons in the superior cervical ganglion had phasic firing properties and large afterhyperpolarizations (AHPs). In addition, 34% of these neurons displayed an afterdepolarization preceding the AHP. Superior cervical ganglion neurons had prominent I M, I A, and I Hcurrents and a linear current-voltage relationship between −60 and −110 mV. Neurons from the thoracic ganglia had significantly smaller action potentials, AHPs, and apparent cell capacitance compared with superior cervical ganglion neurons, and only 18% showed an afterdepolarization. All neurons in superior cervical ganglia and most neurons in celiac ganglia received at least one strong preganglionic input. Nearly one-half the neurons in the celiac ganglion had tonic firing properties, and another 15% had firing properties intermediate between those of tonic and phasic neurons. Most celiac neurons showed significant inward rectification below −90 mV. They also expressed I A, but with slower inactivation kinetics than that of superior cervical or thoracic neurons. Both phasic and tonic celiac ganglion neurons received synaptic inputs via the celiac nerves in addition to strong inputs via the splanchnic nerves. Multivariate statistical analysis revealed that the properties of the action potential, the AHP, and the apparent cell capacitance together were sufficient to correctly classify 80% of neurons according to their ganglion of origin. These results indicate that there is considerable heterogeneity in the morphological, neurochemical, and electrical properties of sympathetic neurons in mice. Although the morphological and neurochemical characteristics of the neurons are likely to be related to their peripheral projections, the expression of particular electrophysiological traits seems to be more closely related to the ganglia within which the neurons occur.
Characterization of l-Homocysteate–Induced Currents in Purkinje Cells From Wild-Type and NMDA Receptor Knockout Mice
Authors: Yuzaki Michisuke , Connor John A.
Published: December 2017

l-Homocysteic acid (HCA), an endogenous excitatory amino acid in the mammalian CNS, potently activates N-methyl-d-aspartate (NMDA) receptors in hippocampal neurons. However, the responses to HCA in Purkinje cells, which lack functional NMDA receptors, have been largely unexplored: HCA may activate conventional non-NMDA receptors by its mixed agonistic action on both NMDA and non-NMDA receptors, or it may activate a novel non-NMDA receptor that has high affinity for HCA. To test these possibilities, we compared the responses to HCA in cultured Purkinje cells with those in hippocampal neurons by using the whole cell patch-clamp technique. To clearly isolate HCA responses mediated by non-NMDA receptors, we complemented pharmacological methods by using neurons from mutant mice (NR−/−) that lack functional NMDA receptors. A moderate dose of HCA (100 μM) induced substantial responses in Purkinje cells. These responses were blocked by non-NMDA receptor antagonists but were insensitive to NMDA receptor antagonists. HCA also activated responses mediated by non-NMDA receptors in both wild-type and NR1−/− hippocampal neurons. HCA responses in Purkinje cells had a pharmacological profile (EC50 and Hill coefficient) very similar to that of non-NMDA receptor components of HCA responses in hippocampal neurons. Moreover, the amplitude of the non-NMDA receptor component of HCA responses was directly correlated with that of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)– and kainate-induced responses in both types of neurons. Finally, in both types of neurons, HCA currents mediated by non-NMDA receptors were potently blocked by the AMPA receptor antagonist GYKI52466. These findings indicate that HCA-activated AMPA receptors in Purkinje cells are similar to those in hippocampal neurons and that there is no distinct HCA-preferring receptor in Purkinje cells. We also found that in hippocampal neurons, the EC50s of HCA for non-NMDA receptors and for NMDA receptors were more similar than originally reported; this finding indicates that HCA is similar to other mixed agonists, such as glutamate. HCA responses may appear to be selective at NMDA receptors in cells that express these receptors, such as hippocampal neurons; in cells that express few functional NMDA receptors, such as Purkinje cells, HCA may appear to be selective at non-NMDA receptors.
Plasticity in the Mediodorsal Thalamo-Prefrontal Cortical Transmission in Behaving Mice
Authors: Herry Cyril , Vouimba Rose-Marie , Garcia René
Published: December 2017

We studied changes in thalamo-prefrontal cortical transmission in behaving mice following both low-frequency stimulation of the mediodorsal thalamus (MD) and during extinction of a conditioned fear response. Electrical stimulation of the MD induces a field potential in the medial prefrontal cortex (mPFC) characterized by two initial negative-positive complexes (N1-P1 and N2-P2) followed by two positive-negative complexes (P2-N3 and P3-N4). The N1-P1 and N2-P2 complexes were identified as resulting from orthodromic and antidromic prefrontal activation, respectively. Because the two complexes were not often easily dissociated, plasticity in the prefrontal synaptic transmission was considered to result from changes in N1-P2 amplitude. Low-frequency thalamic stimulation (1,200 pulses at 2 Hz) produced either long-term (at least 32 min) depression or potentiation of the N1-P2 amplitude. Mice submitted to fear conditioning (tone-shock association), displayed on the first day of extinction (tone-alone presentations) a strong freezing behavior, which decreased progressively, but was still high the following day. Extinction of conditioned fear was accompanied the first day by a depression of prefrontal transmission, which was converted into potentiation the following day. Potentiation of prefrontal transmission lasted at least 24 h following the second day of the fear extinction procedure. In conclusion, low-frequency thalamic stimulation can produce, in behaving mice, either depression or potentiation of prefrontal synaptic transmission. Decrease in prefrontal synaptic transmission observed during the first day of extinction may reflect processing of the high degree of predictiveness of danger (unconditioned stimulus: US) by the aversive conditioned stimulus (CS). However, the subsequent potentiation of transmission in the mPFC may be related to processing of cognitive information such as the CS will no longer be followed by the US, even if emotional response (freezing) to the CS is still high.