bluuebunny/crossref_metadata_2025 huggingface dataset:
Type III sodium channel mRNA is expressed in embryonic but not adult spinal sensory neurons, and is reexpressed following axotomy
Authors: Waxman S. G. , Kocsis J. D. , Black J. A.
Published: December 2017

1. In situ hybridization with subtype-specific probes was used to ask whether there is a change in the types of sodium channels that are expressed in dorsal root ganglion (DRG) neurons after axotomy. 2. Types I and II sodium channel mRNA are expressed at moderate-to-high levels in control DRG neurons of adult rat, but type III sodium channel mRNA is not detectable. 3. When adult rat DRG neurons are examined by in situ hybridization 7–9 days following axotomy, type III sodium channel mRNA is expressed at moderate-to-high levels, in addition to types I and II mRNA that are present at relatively high levels. 4. To determine whether the expression of type III sodium channel mRNA following axotomy represents up-regulation of a gene that had been expressed at earlier developmental stages, we also studied DRG neurons from embryonic (E17) rats. In these embryonic DRG neurons, type I sodium channel mRNA is expressed at low levels, type II mRNA at high levels, and type III at high levels. 5. These results demonstrate altered expression of sodium channel mRNA in DRG neurons following axotomy, and suggest that in at least some DRG neurons, there is a de-differentiation after axotomy that includes a reversion to an embryonic mode of sodium channel expression. Different channel characteristics, as well as an altered spatial distribution of sodium channels, may contribute to the electrophysiological changes that are observed in axotomized neurons.
Protein kinase C inhibitors decrease hyperalgesia and C-fiber hyperexcitability in the streptozotocin-diabetic rat
Authors: Ahlgren S. C. , Levine J. D.
Published: December 2017

1. We have previously demonstrated that although rats with streptozotocin-induced diabetes (STZ-D) have decreased behavioral mechanical nociceptive thresholds (hyperalgesia), their C-fiber primary afferent mechanical (von Frey hair) thresholds are not altered. Instead, when stimulated with a standardized sustained suprathreshold mechanical stimulus, C-fibers from STZ-D rats were found to have an increased number of spikes (hyperexcitability). We suggested that this C-fiber hyperexcitability contributes to the behavioral hyperalgesia and that agents that reverse the hyperalgesia may act by decreasing this hyperexcitability. Because protein kinase C activity contributes to C-fiber afferent excitability, we examined the effect of agents that inhibit protein kinases on behavioral mechanical nociceptive thresholds and on the response of C-fiber afferents to sustained mechanical stimulation. 2. The effects of intradermal injection of two protein kinase inhibitors, staurosporine and protein kinase C pseudosubstrate inhibitor peptide [PKC(19–36)], on behavioral mechanical nociceptive thresholds were determined using the Randall-Selitto paw-withdrawal device. These agents increased the mechanical nociceptive threshold of STZ-D rats in a dose-dependent manner but did not alter nociceptive threshold in control rats. 3. The same agents were tested for their effects on single C-fiber mechanical thresholds and excitability in response to suprathreshold (445 g) mechanical stimulation. Intradermal injection of staurosporine or PKC(19–36) significantly reduced the response of C-fibers from STZ-D rats to sustained suprathreshold mechanical stimulation but did not alter the response of C-fibers from control rats to the same stimulation. Neither agent altered mechanical threshold in C-fibers from either STZ-D or control rats. 4. In this study we found that both the mechanical behavioral hyperalgesia and the C-fiber hyperexcitability to mechanical stimuli seen in STZ-D rats are reduced by agents that inhibit protein kinase C. This evidence supports our hypothesis that C-fiber hyperexcitability, in part mediated by PKC activity, contributes to hyperalgesia in this model of diabetic neuropathy.
Ca2+ cooperativity in neurosecretion measured using photolabile Ca2+ chelators
Authors: Lando L. , Zucker R. S.
Published: December 2017

1. The photolabile Ca2+ chelator DM-nitrophen was injected into crayfish motor neuron terminals and photolyzed with light flashes of different intensity to determine the cooperativity of Ca2+ action in releasing neurotransmitter. 2. Each flash elicited a phasic postsynaptic response resembling an excitatory junctional potential, apparently due to a presynaptic ”spike” in intracellular calcium concentration ([Ca2+]i). 3. When postsynaptic currents were measured under voltage clamp, a Ca2+ cooperativity of approximately 3–4 was inferred from a supralinear dependence of responses on changes in peak [Ca2+]i caused by flashes differing in intensity by 32–46%. 4. A similar Ca2+ cooperativity was inferred from postsynaptic potentials in response to flashes of varying intensity. 5. The time course of transmitter release indicated by flash responses had slightly slower rising and falling phases than excitatory postsynaptic potentials. There was also a slow tail of transmitter release lasting for approximately 200 ms after a flash. 6. This time course was explained quantitatively by simulations of DM-nitrophen photolysis and binding reactions and a model of Ca2+ activation of transmitter release.
Many areas in the human brain respond to visual motion
Authors: Dupont P. , Orban G. A. , De Bruyn B. , Verbruggen A. , Mortelmans L.
Published: December 2017

1. The regions of the human brain responsive to motion were mapped using the H2(15)O position emission tomography (PET) activation technique and compared by viewing a moving random dot pattern with a stationary dot pattern. The stimulus was optimized in dot density and 3 degrees in diameter. 2. In addition to bilateral foci at the border between Brodmann areas 19 and 37, a V1/V2 focus and a focus in the cuneus reported earlier, we observed activations in other visual areas (lower BA 19 and the parieto-occipital fissure) in the cerebellum and in two other, presumed vestibular areas, the posterior bank of lateral sulcus and at the border of BA 2/40. 3. Homologies between monkey and human cortex are discussed.
Presynaptic enhancement of excitatory synaptic transmission by beta-adrenergic receptor activation
Authors: Gereau R. W. , Conn P. J.
Published: December 2017

1. Previous studies have shown that beta-adrenergic receptor activation has many effects on neuronal function in hippocampal area CA1. However, all of the physiological effects of beta-adrenergic receptor activation in this region reported to date have been attributed to postsynaptic mechanisms. A series of studies was performed to test the hypothesis that beta-adrenergic receptor activation also acts presynaptically to enhance excitatory synaptic transmission. 2. Application of the selective beta-adrenergic agonist isoproterenol to hippocampal slices induced an increase in the amplitude of evoked excitatory postsynaptic currents (EPSCs) in CA1 pyramidal cells. This response was potentiated in the presence of a cyclic nucleotide phosphodiesterase inhibitor. Isoproterenol also resulted in the appearance of a late inward synaptic current that likely represents polysynaptically evoked EPSCs. Both the increased amplitude of the monosynaptic EPSC and the appearance of polysynaptic EPSCs in response to isoproterenol were blocked by H89, an inhibitor of adenosine 3',5'-cyclic monophosphate (cAMP)-dependent protein kinase. 3. Isoproterenol induced an increase in the frequency of spontaneous miniature EPSCs but did not affect the amplitude of these currents. In addition, isoproterenol had no effect on currents elicited by direct application of the ionotropic glutamate receptor agonist, (R,S)-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA). 4. These results suggest that activation of presynaptic beta-adrenergic receptors enhances synaptic transmission in area CA1 via activation of cAMP-dependent protein kinase.
Oscillatory synaptic interactions between ventroposterior and reticular neurons in mouse thalamus in vitro
Authors: Warren R. A. , Agmon A. , Jones E. G.
Published: December 2017

1. The thalamic reticular nucleus (RTN) has reciprocal connections with relay neurons in the dorsal thalamus. We used whole cell recording in a mouse in vitro slice preparation maintained at room temperature to study the synaptic interactions between the RTN and the ventroposterior thalamic nucleus (VP) during evoked low-frequency oscillations. 2. After a single electrical stimulus of the internal capsule, postsynaptic potentials (PSPs) were recorded in all VP and RTN neurons. In 76% of slices, there was an initial response followed by recurrent PSPs lasting for up to 8 s and with a frequency of approximately 2 Hz in both the VP and RTN. 3. In RTN neurons the initial response consisted of a fast excitatory postsynaptic potential (EPSP) that generated a burst of action potentials. Recurrent PSPs consisted of barrages of EPSPs that often reached burst threshold. The structure of subthreshold EPSP barrages in RTN neurons suggested that they were generated by bursting VP neurons. 4. In VP neurons the stimulus usually evoked a small EPSP followed by a large inhibitory postsynaptic potential (IPSP) that was often followed by a rebound burst. This initial response was often followed by a series of recurrent IPSPs presumably generated by RTN bursts, because intrinsic inhibitory neurons are absent in rodent VP. 5. IPSPs in VP neurons and recurrent EPSPs in RTN neurons were completely abolished by application of a gamma-aminobutyric acid-A (GABAA) receptor antagonist. A GABAB receptor antagonist produced no or little change in either the initial or recurrent response. 6. Recurrent IPSPs in VP neurons were abolished by glutamate receptor antagonists before the initial IPSP, which always remained stimulus dependent. 7. The dependency of recurring IPSPs in VP and recurring EPSPs in RTN upon GABA-mediated inhibition and excitatory amino acid-mediated excitation, plus the character of recurring EPSPs in the RTN strongly suggest that the recurring events were generated through reverse-reciprocal synaptic interactions between VP and RTN neurons. These synaptic interactions most likely play an important role in thalamic oscillations in behavior.
Effects of conditioning cutaneomuscular stimulation on the soleus H-reflex in normal and spastic paretic subjects during walking and standing
Authors: Fung J. , Barbeau H.
Published: December 2017

1. The modulation of the soleus H-reflex by a conditioning cutaneomuscular stimulation was investigated in 10 normal and 10 spastic paretic subjects who suffered from incomplete spinal cord lesions. The different motor tasks examined were standing, locomotion, and the maintenance of static limb postures to mimic critical gait events. The test soleus H-reflex was obtained by stimulating the tibial nerve in the popliteal fossa with a single 1-ms pulse at an intensity that produced a barely detectable M wave. The conditioning stimulus, consisting of an 11-ms train of three 1-ms pulses at 200 Hz, was delivered to the ipsilateral medial plantar arch, stimulating predominantly the medial plantar nerve, at an innocuous intensity of 2.5–3.0 X sensory threshold and at a conditioning-test delay of 45 ms. 2. During quiet standing, the H-reflex amplitude was inhibited only marginally by the conditioning cutaneomuscular stimulation, not reaching statistical significance in either the normal or spastic group of subjects. Although there was a trend of reflex inhibition in the normal subjects as the conditioning intensity was increased, a reversed trend of reflex facilitation was observed in the spastic patients. 3. During treadmill walking, the conditioned H-reflex was inhibited significantly during all phases in all the normal subjects and in one mildly impaired patient. In the moderately and severely impaired patients, cutaneomuscular stimulation selectively inhibited the soleus H-reflex in the early stance and swing phases, thereby producing a near normal phasic modulation pattern. Such modulatory effects were not present under static gait-mimicking conditions. 4. The task-specific and phase-dependent effects of cutaneomuscular stimulation on the soleus H-reflex in the spinal cord-injured patients revealed strong inhibitory influence on Ia afferents from cutaneomuscular inputs. It is plausible that inhibition occurs at both pre- and postsynaptic levels. 5. It is concluded that normal Ia modulatory mechanisms during locomotion are deficient in spastic spinal cord-injured patients and can partially and artificially be restored by cutaneomuscular stimulation applied to the sole of the foot. This can be used as a functional electrical stimulation (FES) regime in gait rehabilitation.
Surround inhibition among projection neurons is weak or nonexistent in the rat neostriatum
Authors: Jaeger D. , Kita H. , Wilson C. J.
Published: December 2017

1. Antidromic activation of striatal spiny projection neurons by substantia nigra stimulation in vivo did not evoke inhibitory postsynaptic potentials (IPSPs) in the antidromically activated neurons, or in neighboring spiny neurons. 2. More generalized activation of projection cells by stimulation of the efferent pathway in slices did not evoke IPSPs in spiny neurons. Inhibitory mechanisms were operative in these slices, as indicated by the presence of an IPSP component in the orthodromic response to local stimulation. 3. Dual intracellular recordings, obtained from cells located within 50–200 microns of each other in striatal slices also failed to demonstrate any inhibition among striatal spiny cells. Spikes triggered in one spiny neuron by current injection failed to produce any postsynaptic potential in nearby spiny cells at resting or depolarized membrane potentials. Excitatory postsynaptic potentials (EPSPs) evoked by electrical stimulation of the cortex were not affected by spiking of neighboring cells. 4. It is impossible to rule out the presence of inhibition among striatal spiny neurons in all circumstances. However, the absence of demonstrable IPSPs in these experiments argue against the common view that mutual inhibition among spiny neurons is a central organizing principle of striatal function.
Glutamate-induced intracellular acidification of cultured hippocampal neurons demonstrates altered energy metabolism resulting from Ca2+ loads
Authors: Wang G. J. , Randall R. D. , Thayer S. A.
Published: December 2017

1. Glutamate-evoked increases in intracellular free H+ concentration ([H+]i) were recorded from single rat hippocampal neurons grown in primary culture with carboxy SNARF-based dual emission microfluorimetry. The possibility that this acidification resulted from altered energy metabolism was investigated. 2. The response to 10 microM glutamate (delta pH = 0.41 +/- 0.14, mean +/- SD) was blocked by the N-methyl-D-aspartate (NMDA) receptor antagonist CGS19755 (10 microM) and required extracellular Ca2+. 3. Substituting the metabolic inhibitor 2-deoxyglucose for glucose in the extracellular buffer prevented glutamate-induced acidification. 4. Ba2+, which carries charge through Ca2+ channels, including the Ca2+ uniporter on the inner mitochondrial membrane, substituted for Ca2+ in mediating glutamate-induced cytoplasmic acidification. 5. Microinjection of ruthenium red, a compound that blocks mitochondrial Ca2+ sequestration, significantly inhibited glutamate-induced acidification. 6. The mitochondrial uncoupler, carbonyl cyanide-p-trifluoromethoxyphenyl-hydrazone (FCCP, 0.1 microM), mimicked and partially occluded the glutamate-induced [H+]i increase. 7. These findings indicate that glutamate-induced Ca2+ loads are sequestered by mitochondria, uncouple respiration, and produce metabolic acidosis. The glutamate-induced acidification is symptomatic of metabolic stress and may indicate that mitochondria play an important role in glutamate-induced neuronal death.
Subcortical contributions to head movements in macaques. I. Contrasting effects of electrical stimulation of a medial pontomedullary region and the superior colliculus
Authors: Cowie R. J. , Robinson D. L.
Published: December 2017

1. These studies were initiated to understand the neural sites and mechanisms controlling head movements during gaze shifts. Gaze shifts are made by saccadic eye movements with and without head movements. Sites were stimulated electrically within the brain stem of awake, trained monkeys relatively free to make head movements to study the head-movement components of gaze shifts. 2. Electrical stimulation in and around the gigantocellular reticular nucleus evoked head movements in the ipsilateral direction. Gaze shifts were never evoked from these sites, presumably because the vestibulo-ocular reflex compensated. The rough topography of this region included large head movements laterally, small movements medially, downward movements from dorsal sites, and upward movements more ventrally. 3. The initial position of the head influenced the magnitude of the elicited movement with larger movements produced when the head was directed to the contralateral side. Attentive fixation was associated with larger and faster head movements when compared with those evoked during spontaneous behavior. 4. The superior colliculus makes a significant contribution to gaze shifts and has been shown to contribute to head movements. Because the colliculus is a major source of afferents to the gigantocellular reticular nucleus, comparable stimulation studies of the superior colliculus were conducted. When the colliculus was excited, shifts of gaze in the contralateral direction were predominant. These were most often accomplished by saccadic eye movements, however, we frequently elicited head movements that had an average latency 10 ms longer than those elicited from the reticular head movement region. Sites evoking head movements tended to be deeper and more caudal than loci eliciting eye movements. Neither the onset latencies, amplitudes, nor peak velocities of head movements and eye movements were correlated. Gaze shifts evoked from the caudal colliculus with the head free were larger than those elicited from the same site with the head fixed. 5. These studies demonstrate that both the superior colliculus and gigantocellular reticular nucleus mediate head movements. The colliculus plays a role in orienting to external events, and so collicular head movements predominantly were associated with gaze shifts, with the eye and head movements uncoupled. The medullary reticular system may play a role in the integration of a wider range of movements. Head movements from the medullary reticular sites probably participate in several forms of head movements, such as those that are related to postural reflexes, started volitionally, and/or oriented to external events.
Operant conditioning of H-reflex in freely moving rats
Authors: Chen X. Y. , Wolpaw J. R.
Published: December 2017

1. Primates can increase or decrease the spinal stretch reflex and its electrical analogue, the H-reflex (HR), in response to an operant conditioning task. This conditioning changes the spinal cord itself and thereby provides an experimental model for defining the processes and substrates of a learned change in behavior. Because the phenomenon has been demonstrated only in primates, its generality and theoretical implications remain unclear, and its experimental use is restricted by the difficulties of primate research. In response to these issues, the present study explored operant conditioning of the H-reflex in the rat. 2. Seventeen Sprague-Dawley rats implanted with chronic electromyographic (EMG) recording electrodes in one soleus muscle and nerve cuff stimulating electrodes on the posterior tibial nerve were rewarded (either with medial forebrain bundle stimulation or food) for increasing (HRup conditioning mode) or decreasing (HRdown conditioning mode) soleus H-reflex amplitude without change in background EMG or M response (direct muscle response) amplitude. 3. H-reflex amplitude changed appropriately over 3-4 wk. Under the HRup mode, it rose to an average of 158 +/- 54% (mean +/- SD) of initial value, whereas under the HRdown mode it fell to an average of 67 +/- 11% of initial value. Background EMG and M response amplitude did not change. 4. Operant conditioning of the H-reflex in the rat appears similar in rate and final magnitude of change to that observed in the monkey.(ABSTRACT TRUNCATED AT 250 WORDS)
Effects of subcutaneous formalin on the activity of trigeminal brain stem nociceptive neurones in the rat
Authors: Raboisson P. , Dallel R. , Clavelou P. , Sessle B. J. , Woda A.
Published: December 2017

1. The subcutaneous injection of Formalin (5%, 50 microliters) into the receptive field of convergent (wide dynamic range) nociceptive neurons in the spinal dorsal horn has previously been reported to produce a prolonged biphasic response with a time course similar to the observed in behavioral experiments. However, conflicting data in other studies led us to examine the effects of Formalin on the activity of convergent nociceptive neurons at two levels of the trigeminal (V) brain stem complex, namely V subnuclei oralis (Sp5O) and caudalis (Sp5C). 2. Single neuron activity was extracellularly recorded in anesthetized rats. Each neuron was classified as convergent on the basis of its responses to both mechanical and transcutaneous electrical stimuli applied to its mechanoreceptive field (RF). All neurons responded to innocuous and noxious mechanical stimuli and had electrically evoked responses corresponding to both A and C fiber afferent inputs. Seventeen Sp5O and 32 Sp5C convergent neurons received an injection (50 microliters sc) of 5% Formalin into the center of their RF. 3. Three groups of neurons were distinguished: one group that was not activated by the Formalin injection (Sp5O, n = 1; Sp5C, n = 2), another group that responded only with an early and short-lasting response [monophasic neurons: Sp5O, n = 11 (65%); Sp5C, n = 10 (31%)], and a third group that responded with two phases separated by a short period of quiescence [biphasic neurons: Sp5O, n = 5 (29%); Sp5C, n = 20 (62.5%)]. The proportion of biphasic neurons was significantly higher in Sp5C than in Sp5O. 4. The first phases of the Sp5O neurons were not significantly different in terms of duration and frequency from those of the Sp5C neurons. However, duration and discharge frequency of the first phase of biphasic neurons were significantly greater than for monophasic neurons in Sp5C (nonsignificant in Sp5O). The second tonic period of excitation of all biphasic neurons was gradual in outset and offset, and long in duration (23-39 min). The duration of the second phase was significantly longer for the biphasic neurons in Sp5C than for those in Sp5O. 5. Our findings suggest that the mono- and biphasic neurons may have different roles in the transmission of nociceptive information induced by the peripheral injection of Formalin.(ABSTRACT TRUNCATED AT 400 WORDS)
Contraction characteristics and myosin heavy chain composition of rabbit masseter motor units
Authors: Kwa S. H. , Weijs W. A. , Juch P. J.
Published: December 2017

1. We studied isometric twitch peak force (TPF) and twitch contraction time (TCT) of 249 motor units of the masseter muscle in 41 rabbits after extracellular electrical stimulation of single trigeminal motoneurons in the brain stem. In 41 of these units we determined the amount of tension decrease during a partially fused tetanus (sag) and the ratio between peak tetanic force after 2 min of intermittent tetanic stimulation and initial tension (fatigue index). Muscle fibers of 24 motor units were identified by the glycogen depletion method and characterized in serial sections with monoclonal antibodies against type IID, IIA, "cardiac" alpha, and I isoforms of myosin heavy chain (MHC). 2. The motor units had TCTs ranging from 13 to 32 ms. The majority of the units showed forces < 35 mN. The TPFs were larger and varied more for motor units with short and intermediate TCTs than for units with long TCTs. There is a small but statistically significant negative correlation between the motor unit TPF and the TCT. 3. All units exhibited "sag" and, with the exeption of one, had fatigue indexes > 0.75. The studied rabbit masseter motor units can therefore be classified as fast, fatigue-resistant, except for one that belonged to the FF (fast, fatigable) category. No slow units were represented in the sample pool. Significant correlations were not found either between TCT and the amount of sag or between TCT and the fatigue index. 4. Immunohistochemical analysis showed that the FF unit had fibers containing only IID-MHC. Five other units were found with a single MHC--three with IIA-MHC and two with alpha-MHC. In three other units all fibers showed one combination of two MHCs (1 IIA/IID, 1 IIA/alpha, and 1 alpha/I). The remaining 15 units contained two MHCs spread unevenly over the constituting fibers. Large variations in myosin composition of fibers within one motor unit cast doubts on the presumed dominant neuronal influence on myosin expression in the adult animal. 5. We found a close, statistically significant correlation between the TCT and the estimated MHC content of the units: the TCT was 13 ms for the IID unit, 18 ms for the pure IIA units, and 28 ms for the pure alpha units. Units with two MHCs had intermediate TCTs; units with alpha/I-MHC mixtures had TCTs of 29-30 ms. No pure MHC-I units were identified.(ABSTRACT TRUNCATED AT 400 WORDS)
Control of limb dynamics in normal subjects and patients without proprioception
Authors: Sainburg R. L. , Ghilardi M. F. , Poizner H. , Ghez C.
Published: December 2017

1. We recently showed that patients lacking proprioceptive input from their limbs have particular difficulty performing multijoint movements. In a pantomimed slicing gesture requiring sharp reversals in hand path direction, patients showed large hand path distortions at movement reversals because of failure to coordinate the timing of the separate reversals at the shoulder and elbow joints. We hypothesized that these reversal errors resulted from uncompensated effects of inertial interactions produced by changes in shoulder joint acceleration that were transferred to the elbow. We now test this hypothesis and examine the role of proprioceptive input by comparing the motor performance of five normal subjects with that of two patients with large-fiber sensory neuropathy. 2. Subjects were to trace each of six template lines presented randomly on a computer screen by straight overlapping out-and-back movements of the hand on a digitizing tablet. The lines originated from a common starting position but were in different directions and had different lengths. Directions and lengths were adjusted so that tracing movements would all require the same elbow excursion, whereas shoulder excursion would vary. The effects of varying interaction torques on elbow kinematics were then studied. The subject's dominant arm was supported in the horizontal plane by a low-inertia brace equipped with ball bearing joints and potentiometers under the elbow and shoulder. Hand position was monitored by a magnetic pen attached to the brace 1 cm above a digitizing tablet and could be displayed as a screen cursor. Vision of the subject's arm was blocked and the screen cursor was blanked at movement onset to prevent visual feedback during movement. Elbow joint torques were calculated from joint angle recordings and compared with electromyographic recordings of elbow joint musculature. 3. In control subjects, outward and inward paths were straight and overlapped the template lines regardless of their direction. As prescribed by the task, elbow kinematics remained the same across movement directions, whereas interaction torques varied substantially. The timing of the onsets of biceps activity and the offsets of triceps activity during elbow flexion varied systematically with direction-dependent changes in interaction torques. Controls exploited or dampened these interaction torques as needed to meet the kinematic demands of the task. 4. In contrast, the patients made characteristic errors at movement reversals that increased systematically across movement directions. These reversal errors resulted from improper timing of elbow and shoulder joint reversals.(ABSTRACT TRUNCATED AT 400 WORDS)
Temporal encoding of movement kinematics in the discharge of primate primary motor and premotor neurons
Authors: Fu Q. G. , Flament D. , Coltz J. D. , Ebner T. J.
Published: December 2017

1. Several neurophysiological studies of the primary motor and premotor cortices have shown that the movement parameters direction, distance, and target position are correlated with the discharge of single neurons. Here we investigate whether the correlations with these parameters occur simultaneously (i.e., parallel processing), or sequentially (i.e., serial processing). 2. The single-unit data used for the analyses presented in this paper are the same as those used in our earlier study of neuronal specification of movement parameters. We recorded the activity of single neurons in the primary motor and premotor cortices of two rhesus monkeys (Macaca mulatta) while the animals performed reaching movements made in a horizontal plane. Specifically, the animals moved from a centrally located start position to 1 of 48 targets (1 cm2) placed at eight different directions (0-360 degrees in 45 degrees intervals) and six distances (1.4-5.4 cm in 0.8-cm increments) from the start position. 3. We analyzed 130 task-related cells; of these, 127 (99 in primary motor cortex, 28 near the superior precentral sulcus) had average discharges that were significantly modulated with the movement and were related to movement direction, distance, or target position. To determine the temporal profile of the correlation of each cell's discharge with the three parameters, we performed a regression analysis of the neural discharge. We calculated partial R2s for each parameter and the total R2 for the model as a function of time. 4. The discharge of the majority of units (73.2%) was significantly correlated for some time with all three parameters. Other units were found that correlated with different combinations of pairs of parameters (21.3%), and a small number of units appeared to code for only one parameter (5.5%). There was no obvious difference in the presence of correlations between cells recorded in the primary motor versus premotor cortices. 5. On average we found a clear temporal segregation and ordering in the onset of the parameter-related partial R2 values: direction-related discharge occurred first (115 ms before movement onset), followed sequentially by target position (57 ms after movement onset) and movement distance (248 ms after movement onset). Some overlap in the timing of the correlation of these parameters was evident. We found a similar sequential ordering for the latency of the peak of the R2 curves (48, 254, and 515 ms after movement onset, respectively, for direction, target position, and distance).(ABSTRACT TRUNCATED AT 400 WORDS)
Cholinergic contribution to excitation in a spinal locomotor central pattern generator in Xenopus embryos
Authors: Perrins R. , Roberts A.
Published: December 2017

1. We have investigated whether in Xenopus embryos, spinal interneurons of the central pattern generator (CPG) receive cholinergic or electrical excitatory input during swimming. The functions of cholinergic excitation during swimming were also investigated. 2. Intracellular recordings were made from rhythmically active presumed premotor interneurons in the dorsal third of the spinal cord. After locally blocking inhibitory potentials with 2 microM strychnine and 40 microM bicuculline, the reliability of spike firing and the amplitude of fast, on-cycle, excitatory postsynaptic potentials (EPSPs) underlying the single on-cycle spikes were measured during fictive swimming. 3. The nicotinic antagonists d-tubocurarine and dihydro-beta-erythroidine (DH beta E, both 10 microM) reversibly reduced the reliability of the spike firing during swimming and reduced the amplitude of the on-cycle EPSP by 16%. DH beta E also reduced the EPSP amplitude in spinalized embryos by 22%. These results indicate that interneurons receive rhythmic cholinergic excitation from a source within the spinal cord. 4. Combined applications of nicotinic and excitatory amino acid (EAA) antagonists or cadmium (Cd2+, 100-200 microM) resulted in complete block of the fast EPSP, suggesting that interneurons do not receive electrical excitation. 5. The nicotinic antagonists mecamylamine and d-tubocurarine (both 5 microM) reduced the duration of episodes of fictive swimming recorded from the ventral roots, in spinal embryos. When applied in the middle of a long episode, d-tubocurarine decreased the swimming frequency, ruling out an effect on the initiation pathway. The cholinesterase inhibitor eserine (10 microM) increased the duration of swimming episodes.(ABSTRACT TRUNCATED AT 250 WORDS)
Computer simulations of morphologically reconstructed CA3 hippocampal neurons
Authors: Migliore M. , Cook E. P. , Jaffe D. B. , Turner D. A. , Johnston D.
Published: December 2017

1. We tested several hypotheses with respect to the mechanisms and processes that control the firing characteristics and determine the spatial and temporal dynamics of intracellular Ca2+ in CA3 hippocampal neurons. In particular, we were interested to know 1) whether bursting and nonbursting behavior of CA3 neurons could be accounted for in a morphologically realistic model using a number of the known ionic conductances; 2) whether such a model is robust across different cell morphologies; 3) whether some particular nonuniform distribution of Ca2+ channels is required for bursting; and 4) whether such a model can reproduce the magnitude and spatial distribution of intracellular Ca2+ transients determined from fluorescence imaging studies and can predict reasonable intracellular Ca2+ concentration ([Ca2+]i) distribution for CA3 neurons. 2. For this purpose we have developed a highly detailed model of the distribution and densities of membrane ion channels in hippocampal CA3 bursting and nonbursting pyramidal neurons. This model reproduces both the experimentally observed firing modes and the dynamics of intracellular Ca2+. 3. The kinetics of the membrane ionic conductances are based on available experimental data. This model incorporates a single Na+ channel, three Ca2+ channels (CaN, CaL, and CaT), three Ca(2+)-independent K+ channels (KDR, KA, and KM), two Ca(2+)-dependent K+ channels (KC and KAHP), and intracellular Ca(2+)-related processes such as buffering, pumping, and radial diffusion. 4. To test the robustness of the model, we applied it to six different morphologically accurate reconstructions of CA3 hippocampal pyramidal neurons. In every neuron, Ca2+ channels, Ca(2+)-related processes, and Ca(2+)-dependent K+ channels were uniformly distributed over the entire cell. Ca(2+)-independent K+ channels were placed on the soma and the proximal apical dendrites. For each reconstructed cell we were able to reproduce bursting and nonbursting firing characteristics as well as Ca2+ transients and distributions for both somatic and synaptic stimulations. 5. Our simulation results suggest that CA3 pyramidal cell bursting behavior does not require any special distribution of Ca(2+)-dependent channels and mechanisms. Furthermore, a simple increase in the Ca(2+)-independent K+ conductances is sufficient to change the firing mode of our CA3 neurons from bursting to nonbursting. 6. The model also displays [Ca2+]i transients and distributions that are consistent with fluorescent imaging data. Peak [Ca2+]i distribution for synaptic stimulation of the nonbursting model is broader when compared with somatic stimulation. Somatic stimulation of the bursting model shows a broader distribution in [Ca2+]i when compared with the nonbursting model.(ABSTRACT TRUNCATED AT 400 WORDS)
Development and characterization of pathways descending to the spinal cord in the embryonic chick
Authors: Sholomenko G. N. , O'Donovan M. J.
Published: December 2017

1. We used an isolated preparation of the embryonic chick brain stem and spinal cord to examine the origin, trajectory, and effects of descending supraspinal pathways on lumbosacral motor activity. The in vitro preparation remained viable for < or 24 h and was sufficiently stable for electrophysiological, pharmacological, and neuroanatomic examination. In this preparation, as in the isolated spinal cord, spontaneous episodes of both forelimb and hindlimb motor activity occur in the absence of phasic afferent input. Motor activity can also be evoked by brain stem electrical stimulation or modulated by the introduction of neurochemicals to the independently perfused brain stem. 2. At embryonic day (E)6, lumbosacral motor activity could be evoked by brain stem electrical stimulation. At E5, neither brain stem nor spinal cord stimulation evoked activity in the lumbosacral spinal cord, although motoneurons did express spontaneous activity. 3. Lesion and electrophysiological studies indicated that axons traveling in the ventral cord mediated the activation of lumbosacral networks by brain stem stimulation. 4. Partition of the preparation into three separately perfused baths, using a zero-Ca2+ middle bath that encompassed the cervical spinal cord, demonstrated that the brain stem activation of spinal networks could be mediated by long-axoned pathways connecting the brain stem and lumbosacral spinal cord. 5. Using retrograde tracing from the spinal cord combined with brain stem stimulation, we found that the brain stem regions from which spinal activity could be evoked lie in the embryonic reticular formation close to neurons that send long descending axons to the lumbosacral spinal cord. The cells giving rise to these descending pathways are found in the ventral pontine and medullary reticular formation, a region that is the source of reticulospinal neurons important for motor activity in adult vertebrates. 6. Electrical recordings from this region revealed that the activity of some brain stem neurons was synchronized with the electrical activity of lumbosacral motoneurons during evoked or spontaneous episodes of rhythmic motor activity. 7. Both brain stem and spinal cord activity could be modulated by selective application of the glutamate agonist N-methyl-D-aspartate to the brain stem, supporting the existence of functionally active descending projections from the brain stem to the spinal cord. It is not yet clear what role the brain stem activity carried by these pathways has in the genesis and development of spinal cord motor activity.
Neurotensin-induced modulation of spinal neurons and fictive locomotion in the lamprey
Authors: Barthe J. Y. , Grillner S.
Published: December 2017

1. Neurotensin containing interneurons are present in the spinal cord of both mammalian and nonmammalian vertebrates, but as yet little is known about their functional role. In this study we examine the effect of neurotensin on spinal cells and on the central pattern generator for locomotion in the lamprey spinal cord. 2. Bath application of neurotensin (10(-8) to 10(-6) M) slowed down the fictive locomotor activity induced by the glutamate agonist N-methyl-D-aspartate in the isolated spinal cord. The duration of the bursts of activity in the ventral roots increased in proportion to the increase of the locomotor cycle duration. 3. Intracellular recordings from grey matter neurons and intraspinal stretch receptors neurons showed that neurotensin induced a depolarization [4.4 +/- 0.5 (SE) mV, n = 19]. This depolarization could still be obtained after a blockade of voltage-sensitive sodium channels with tetrodotoxin (1.5 +/- 0.5 mV; n = 6), and after removal of calcium (2.8 +/- 0.4 mV; n = 5). Moreover no consistent change occurred in the fast and slow phase of the afterhyperpolarization (AHP) both of which are carried by potassium currents.
Nonclock behavior of inferior olive neurons: interspike interval of Purkinje cell complex spike discharge in the awake behaving monkey is random
Authors: Keating J. G. , Thach W. T.
Published: December 2017

1. Complex spikes of cerebellar Purkinje cells recorded from awake, behaving monkeys were studied to determine the extent to which their discharge could be quantified as periodic. Three Rhesus monkeys were trained to perform up to five different tasks involving rotation of the wrist in relation to a visual cue. Complex spike activity was recorded during task performance and intertrial time. Interspike intervals were determined from the discharge of each of 89 Purkinje cells located throughout lobules IV, V, and VI. Autocorrelation and Fourier transform of the autocorrelation function were performed on the data. In addition, the activity from one cell was transformed so that the discharge occurred on the beat of a 10-Hz clock, and in a further transformation, on the beat of a noisy 10-Hz clock. These transformed data were then analyzed as described above. 2. Fourier transform of the autocorrelogram function of the data that had been transformed to a 10-Hz clock, and that of the noisy 10-Hz clock, both showed a prominent peak at 10 Hz. However, the autocorrelograms and the Fourier transforms of the autocorrelogram functions failed to reveal a prominent periodicity for the actual discharge of any of cells, at any frequency up to 100 Hz: the discharge appeared random with respect to the interspike interval. The discharge was not random with respect to behavior. Complex spike activity was commonly time locked to the start of wrist movement. We examined this discharge to see whether oscillatory discharge could be seen after alignment of the data on the start of wrist movement, or after alignment of the data on the complex spike occurring peri-start of wrist movement. No oscillation was seen for either alignment. 3. The inferior olive, which sends its climbing fibers to the cerebellum, has been implicated in such different activities as 1) pathological tremor of the soft palate, 2) physiological tremor, 3) the normal initiation of all bodily movement, and 4) motor learning. Previous work in pharmacologically or surgically treated animals has shown that, under some conditions, the discharge of these neurons is periodic and synchronous. This firing pattern has been interpreted to support a role in the first two activities. But measurements reported here in the awake monkey show just the opposite: the discharge is aperiodic to the extent of being random. As such, the inferior olive cannot be a "motor clock" in the general role that has been proposed.(ABSTRACT TRUNCATED AT 400 WORDS)
Motoneuron properties after operantly conditioned increase in primate H-reflex
Authors: Carp J. S. , Wolpaw J. R.
Published: December 2017

1. Monkeys can increase (HRup conditioning mode) or decrease (HRdown conditioning mode) the triceps surae (TS) H-reflex in response to an operant conditioning task. This conditioning modifies the spinal cord. To define this spinal cord plasticity and its role in the behavioral change (H-reflex increase or decrease), we have recorded intracellularly from TS motoneurons in conditioned animals. The present report describes data from HRup animals and compares them with data from previously studied naive (NV; i.e., unconditioned) animals. 2. Thirteen monkeys (Macaca nemestrina, male, 3.8-7.1 kg) were exposed to the HRup conditioning mode, in which reward occurred when H-reflex size in one leg (i.e., the trained leg) was above a criterion value. Conditioning was successful (i.e., increase of > or = 20%) in 12 of the 13 animals. At the end of conditioning, H-reflex size in the trained leg averaged 188% of its initial value, whereas size in the control leg averaged 134% of its initial value. 3. Intracellular recordings were obtained from 136 TS motoneurons on trained (UT + motoneurons) and control (UC + motoneurons) sides of the successful animals. Measurements included axonal conduction velocity, input resistance, time constant, electrotonic length, rheobase, firing threshold to current injection, afterhyperpolarization duration and amplitude, and composite homonymous and heteronymous excitatory postsynaptic potential (EPSP) size and shape. Results were compared with intracellular data from NV animals.(ABSTRACT TRUNCATED AT 250 WORDS)
Direction biases of X and Y type retinal ganglion cells in the cat
Authors: Shou T. , Leventhal A. G. , Thompson K. G. , Zhou Y.
Published: December 2017

1. It has been reported that in the cat only a specialized group of retinal ganglion cells constituting approximately 1% of the overall population are direction sensitive. Two major groups of retinal ganglion cells, the X and Y cells, have been reported not to be sensitive to the direction of stimulus motion. 2. We recorded action potentials of retinal ganglion cells intraocularly. We studied quantitatively the visual responses elicited by drifting sinusoidal gratings of various spatial frequencies, bars, and spots. 3. The results confirm previous reports that most cat retinal ganglion cells exhibit orientation biases when tested with gratings of relatively high spatial frequency. 4. Additionally, we find that 22% of X and 34% of Y type retinal ganglion cells exhibit direction biases. Overall, Y cells displayed significantly stronger direction biases than did X cells. 5. In general, direction biases are clearest when the test gratings are of relatively low spatial frequency. 6. The direction biases of X and Y cells subserving the central 15 degrees of retina were weaker than those of cells subserving more peripheral regions. 7. The direction-biased responses of cat ganglion cells were similar to those of X and Y type relay cells in the cat dorsal lateral geniculate nucleus (LGNd). Thus we suggest that the direction biases of LGNd cells are a reflection of their retinal inputs.