bluuebunny/crossref_metadata_2025 huggingface dataset:
Kinetic and pharmacological properties of low voltage-activated Ca2+ current in rat clonal (GH3) pituitary cells
Authors: Herrington J. , Lingle C. J.
Published: December 2017

1. Low voltage-activated (LVA) Ca2+ current in clonal (GH3) pituitary cells was studied with the use of the whole-cell recording technique. The use of internal fluoride to facilitate the rundown of high voltage-activated (HVA) Ca2+ current allowed the study of LVA current in virtual isolation. 2. In 10 mM [Ca2+]o, detectable LVA current begins to appear at about -50 mV, with half-maximal activation occurring at -33 mV. The time course of activation was best described by a Hodgkin-Huxley expression with n = 3, suggesting that at least three closed states must be traversed before channel opening. 3. Deactivation was found to vary exponentially with membrane potential between -60 and -160 mV, indicating that channel closing is rate-limited by a single, voltage-dependent transition. 4. Onset and removal of inactivation between -40 and -130 mV were best described by the sum of two exponentials. Between -80 and -130 mV, both components of removal of inactivation showed little voltage dependence, with time constants of approximately 200-300 ms and 1-2 s. At membrane potentials above -40 mV, a single component of inactivation onset was detected. This component was voltage independent between -20 and +20 mV (tau = 22 ms). Thus inactivation of LVA current is best described by multiple, voltage-in-dependent processes. 5. Significant inactivation of LVA current occurred at -65 mV without detectable macroscopic current. This suggests that inactivation is not strictly coupled to channel opening. 6. Peak LVA current increased with increasing [Ca2+]o, with saturation approximately 50 mM. The Ca(2+)-dependence of peak LVA current was reasonably well described by a single-site binding isotherm with half-maximal LVA current at approximately 7 mM. 7. LVA current in GH3 cells was largely resistant to blockade by Ni2+. The relative potency of inorganic cations in blocking GH3 LVA current was (concentrations which produced 50% block): La3+ (2.4 microM) greater than Cd2+ (188 microM) greater than Ni2+ (777 microM). 8. Several organic agents, including putative LVA blockers, HVA current blockers and various anesthetic agents, were tested for their ability to block LVA current. The concentrations that produced 50% block are as follows: nifedipine (approximately 50 microM), D600 (51 microM), diltiazem (131 microM), octanol (244 microM), pentobarbital (985 microM), methoxyflurane (1.41 mM), and amiloride (1.55 mM). Phenytoin and ethosuximide produced 36 and 10% block at 100 microM and 2.5 mM, respectively.(ABSTRACT TRUNCATED AT 400 WORDS)
Histamine activates chloride conductance in motor neurons of the lobster cardiac ganglion
Authors: Hashemzadeh-Gargari H. , Freschi J. E.
Published: December 2017

1. Individual motor neurons of the lobster cardiac ganglion were voltage clamped with two microelectrodes. Superfusion of histamine evoked a concentration-dependent membrane current. The mean effective concentration (EC50) for the concentration-effect relationship was 28 microM. 2. The amplitude and polarity of the histamine-activated current depended on intracellular and extracellular Cl- concentration. The membrane potential at which the current polarity reversed was a function of the Cl- equilibrium potential. 3. The histamine-activated Cl- conductance was voltage dependent, increasing with depolarization. As a consequence, the histamine-evoked current showed outward rectification. 4. We conclude that histamine activates a Cl- conductance with biophysical properties similar to the crustacean Cl- conductance activated by gamma-aminobutyric acid (GABA) and to the histamine responses described in lobster olfactory and stomatogastric neurons. 5. The response to histamine was competitively inhibited (IC50 = 7 microM) by cimetidine, an H2 subtype inhibitor in mammals. Ranitidine, pyrilamine, chlorpheniramine, diphenhydramine, and cyproheptadine were 50-100 times less potent than cimetidine. Tubocurarine, a Cl- channel blocker, blocked with an IC50 of 20 microM, but picrotoxin did not begin to inhibit the histamine response until concentrations exceeded 0.1 mM. 6. These results suggest that the response cannot easily be classified with the use of the pharmacological categories developed in mammals. Like the Cl(-)-dependent responses to various neurotransmitters in a number of invertebrates, the histamine response in the lobster cardiac ganglion was inhibited by tubocurarine. 7. Both GABA and histamine had similar effects on the motor neurons, but only GABA inhibited pacemaker bursts. In this respect, GABA more resembles the endogenous inhibitory postsynaptic potential.(ABSTRACT TRUNCATED AT 250 WORDS)
Electrophysiology of glutamate neurotoxicity in vitro: induction of a calcium-dependent extended neuronal depolarization
Authors: Coulter D. A. , Sombati S. , DeLorenzo R. J.
Published: December 2017

1. Physiological responses of hippocampal pyramidal neurons in primary culture to prolonged glutamate (GLU) exposure (500 microM in all experiments) were studied with the use of patch electrodes and whole-cell current-clamp recording techniques. In some experiments, perforated patch recordings were employed with electrodes containing the pore-forming antibiotic nystatin. 2. After washout of GLU after a 10-min exposure, pyramidal neurons remained depolarized by greater than or equal to 20 mV from rest for the duration of the recording (30 min to less than 4 h). This depolarization was accompanied by a 57.8% increase in membrane conductance and was termed an extended neuronal depolarization (END). The percentage of neurons in which END was induced varied with the duration of GLU exposure, with a 4-, 6-, 8-, 10-, and 20-min GLU exposure eliciting END in 12.5, 41.7, 81.8, 100, and 100% of neurons. END induction appeared to be an all-or-none phenomenon, because END levels did not differ when compared across GLU exposure times. 3. During the END, cells retained both the ability to fire action potentials and the ability to respond to GLU, appeared viable when examined anatomically, and still excluded vital dyes. This supports the conclusion that END is not a nonspecific consequence of cell death. Rather, END is a discrete physiological process triggered by prolonged GLU exposure. The results raise questions concerning the reversibility of END induction, i.e., can neurons be "rescued" once END is induced, or will these cells inevitably go on to die? 4. END induction was dependent on a rise in intracellular free calcium ([Ca]i). END was prevented by strong buffering of [Ca]i or by substitution of external Ba2+ for Ca2+. However, substitution of Mn2+ for Ca2+ still permitted END induction. In cells recorded with the perforated-patch technique, maintaining normal [Ca]i levels, END could be induced, but less readily than under unbuffered [Ca]i conditions. 5. END could not be induced by a 10- to 20-min current-clamp depolarization to 0 mV, nor by 10-min GLU application while the membrane potential was voltage clamped at rest in a solution containing 1 mM Mg2+. In addition, END induction by GLU could be blocked by application of MK-801 (10-30 microM) but not 6-cyano-7-nitroquinoxaline-2,3-dione [CNQX (100-200 microM)]. 6. The dependence of both delayed neuronal cell death and END induction on GLU exposure duration were similar.(ABSTRACT TRUNCATED AT 400 WORDS)
Nicotinic acetylcholine receptors are directly affected by agents used to study protein phosphorylation
Authors: Reuhl T. O. , Amador M. , Moorman J. R. , Pinkham J. , Dani J. A.
Published: December 2017

1. Messenger RNAs for the subunits of the muscle nicotinic acetylcholine receptor (nAChR) were expressed in Xenopus oocytes. A two-electrode voltage clamp was used to measure the acetylcholine (ACh)-induced macroscopic currents. In addition, patch-clamp techniques were used to study nAChR channels in whole cells and in outside-out patches excised from BC3H-1 cells and in patches from oocytes. The single-channel and macroscopic currents were modified by compounds that are usually used to study protein phosphorylation. 2. IBMX (3-isobutyl-1-methylxanthine) is a phosphodiesterase inhibitor. Because it elevates the intracellular concentration of adenosine 3',5'-cyclic monophosphate (cAMP), IBMX is often used to indirectly activate cAMP-dependent protein kinase. H-7 [1-(5-isoquinolinylsulfonyl)-2-methylpiperazine] is mainly used as a rather nonspecific inhibitor of protein kinase activity. Both IBMX and H-7 directly inhibit ACh-induced currents independent of their action on phosphorylation. This direct effect of these compounds is similar to the previously reported inhibition of nAChRs and K+ channels by forskolin, which is commonly used to elevate intracellular cAMP. 3. Macroscopic currents induced in the oocytes by 50 microM ACh had an average peak current of 605 nA, and the currents decayed biexponentially with tau of 15 and 225 s. When 300 microM H-7 was added simultaneously with the ACh, the average peak current was 228 nA and the tau were 1 and 108 s. When 500 microM IBMX was added simultaneously with the ACh, the average peak current was 308 nA and the tau were 9 and 237 s. H-7 and IBMX decreased the peak current induced by ACh, and the compounds increased the decay rate of the current. Under these experimental conditions, the IC50 for reduction of peak amplitude at -30 mV was 160 microM for H-7 and 475 microM for IBMX. 4. H-7 preferentially inhibits the open conformation of the nAChR channel, but there is also some inhibition of the closed channel. The inhibition is voltage dependent: inhibition decreases e-fold per 34 mV depolarization. H-7 does not become trapped within the closed channel and does not significantly alter desensitization under our experimental conditions. 5. H-7 and IBMX interrupt or terminate single-channel openings in membrane patches excised from oocytes or BC3H-1 cells.(ABSTRACT TRUNCATED AT 400 WORDS)
Neural compensation for fatigue-induced changes in muscle stiffness during perturbations of elbow angle in human
Authors: Kirsch R. F. , Rymer W. Z.
Published: December 2017

1. The contribution to muscle force regulation provided by reflex pathways was studied in the elbow flexor muscles of seven normal human subjects, with the use of voluntary fatigue to induce a deficit in the force-generating capability of these muscles. To estimate the changes in the mechanical state of the muscle and the compensatory actions taken by reflex pathways to minimize the impact of fatigue, stochastic and "step" angular perturbations were applied to the joint, and the resulting joint stiffness and electromyographic (EMG) responses were compared before and after fatigue. 2. The magnitude of contractile fatigue, induced by repeatedly lifting a weight via a pulley system, was quantified by comparing the slope of the isometric torque-EMG relationship before and after fatigue. The exercise routine was quite effective in producing severe and long-lasting fatigue, with average percentage changes in the isometric torque-EMG slope of 210-306% for biceps and 129-205% for brachioradialis, depending on the point in time examined. 3. The torque response to a rapid step stretch of the elbow joint was quite similar before and after fatigue for the time interval before reflex action (less than 20 ms after stretch onset), suggesting that intrinsic muscle stiffness for a given mean torque level was not changed by fatigue. The steady-state torque level attained after completion of the stretch was always decreased after fatigue, indicating a decrease in the reflex component of joint stiffness, but this decrease was small compared with the change in the isometric torque-EMG relationship and was accompanied by a significantly larger incremental EMG response after fatigue. This increase in incremental EMG after fatigue was found to be of reflex origin, with activation-related reflex gain changes apparently playing a significant role only at low contraction levels. 4. Torque and angle responses recorded during stochastic perturbations were used to identify elbow joint compliance impulse responses. A second-order mechanical model was fit to each impulse response, and the parameters representing joint inertia, elastic stiffness, and viscous stiffness were used to summarize changes in joint mechanical properties as the mean contraction level was varied. For a perturbation with a relatively wide bandwidth (0-25 Hz), fatigue had little or no effect on the form of the compliance impulse response, apparently because the stimulus disabled reflex force generation in elbow flexor muscles, whereas a perturbation with a more restricted bandwidth (0-10 Hz) demonstrated consistent decreases in joint stiffness after fatigue.(ABSTRACT TRUNCATED AT 400 WORDS)
5-HT modulation of hyperpolarization-activated inward current and calcium-dependent outward current in a crustacean motor neuron
Authors: Kiehn O. , Harris-Warrick R. M.
Published: December 2017

1. Serotonergic modulation of a hyperpolarization-activated inward current, Ih, and a calcium-dependent outward current, Io(Ca), was examined in the dorsal gastric (DG) motor neuron, with the use of intracellular recording techniques in an isolated preparation of the crab stomatogastric ganglion (STG). 2. Hyperpolarization of the membrane from rest with maintained current pulses resulted in a slow time-dependent relaxation back toward rest and a depolarizing overshoot after termination of the current pulse. In voltage clamp, hyperpolarizing commands negative to approximately -70 mV caused a slowly developing inward current, Ih, which showed no inactivation. Repolarization back to the holding potential of -50 mV revealed a slow inward tail current. 3. The reversal potential for Ih was approximately -35 mV. Raising extracellular K+ concentration ([K+]o) from 11 to 22 mM enhanced, whereas decreasing extracellular Na+ concentration ([Na+]o) reduced the amplitude of Ih. These results indicate that Ih in DG is carried by both K+ and Na+ ions. 4. Bath application of serotonin (5-HT; 10 microM) caused a marked increase in the amplitude of Ih through its active voltage ranges. 5. The time course of activation of Ih was well fitted by a single exponential function and strongly voltage dependent. 5-HT increased the rate of activation of Ih. 5-HT also slowed the rate of deactivation of the Ih tail on repolarization to -50 mV. 6. The activation curve for the conductance (Gh) underlying Ih was obtained by analyzing tail currents. 5-HT shifted the half activation for Gh from approximately -105 mV in control to -95 mV, resulting in an increase in the amplitude of Gh active at rest. 7. Two to 4 mM Cs+ abolished Ih, whereas barium (200 microM to 2 mM) had only weak suppressing effects on Ih. Concomitantly, Cs+ also blocked the 5-HT-induced inward current and conductance increase seen at voltages negative to rest. In current clamp, Cs+ caused DG to hyperpolarize 3-4 mV from rest, suggesting that Ih is partially active at rest and contributes to the resting membrane potential. 8. Depolarizing voltage commands from a holding potential of -50 mV resulted in a total outward current (Io) with an initial transient component and a sustained steady-state component. Application of 5-HT reduced both the transient and sustained components of Io. 9. Io was reduced by 10-20 mM tetraethylammonium (TEA), suggesting that it is primarily a K+ current.(ABSTRACT TRUNCATED AT 400 WORDS)
Serial and parallel processing of tactual information in somatosensory cortex of rhesus monkeys
Authors: Pons T. P. , Garraghty P. E. , Mishkin M.
Published: December 2017

1. Selective ablations of the hand representations in postcentral cortical areas 3a, 3b, 1, and 2 were made in different combinations to determine each area's contribution to the responsivity and modality properties of neurons in the hand representation in SII. 2. Ablations that left intact only the postcentral areas that process predominantly cutaneous inputs (i.e., areas 3b and 1) yielded SII recording sites responsive to cutaneous stimulation and none driven exclusively by high-intensity or "deep" stimulation. Conversely, ablations that left intact only the postcentral areas that process predominantly deep receptor inputs (i.e., areas 3a and 2) yielded mostly SII recording sites that responded exclusively to deep stimulation. 3. Ablations that left intact only area 3a or only area 2 yielded substantial and roughly equal reductions in the number of deep receptive fields in SII. By contrast, ablations that left intact only area 3b or only area 1 yielded unequal reductions in the number of cutaneous receptive fields in SII: a small reduction when area 3b alone was intact but a somewhat larger one when only area 1 was intact. 4. Finally, when the hand representation in area 3b was ablated, leaving areas 3a, 1, and 2 fully intact, there was again a substantial reduction in the encounter rate of cutaneous receptive fields. 5. The partial ablations often led to unresponsive sites in the SII hand representation. In SII representations other than of the hand no such unresponsive sites were found and there were no substantial changes in the ratio of cutaneous to deep receptive fields, indicating that the foregoing results were not due to long-lasting postsurgical depression or effects of anesthesia. 6. The findings indicate that modality-specific information is relayed from postcentral cortical areas to SII along parallel channels, with cutaneous inputs transmitted via areas 3b and 1, and deep inputs via areas 3a and 2. Further, area 3b provides the major source of cutaneous input to SII, directly and perhaps also via area 1. 7. The results are in line with accumulating anatomic and electrophysiologic evidence pointing to an evolutionary shift in the organization of the somatosensory system from the general mammalian plan, in which tactile information is processed in parallel in SI and SII, to a new organization in higher primates in which the processing of tactile information proceeds serially from SI to SII. The presumed functional advantages of this evolutionary shift are unknown.
Involvement of protein kinase C in serotonin-induced spike broadening and synaptic facilitation in sensorimotor connections of Aplysia
Authors: Sugita S. , Goldsmith J. R. , Baxter D. A. , Byrne J. H.
Published: December 2017

1. Plasticity at the connections between sensory neurons and their follower cells in Aplysia has been used extensively as a model system to examine mechanisms of simple forms of learning. Earlier studies have concluded that serotonin (5-HT) is a key modulatory transmitter and that it exerts its short-term actions via cAMP-dependent activation of protein kinase A. Subsequently, it has become clear that other kinase systems such as protein kinase C (PKC) also may be involved in the actions of 5-HT. 2. Application of phorbol esters, which activate PKC, produced a slowly developing spike broadening but had little effect on excitability (a process known to be primarily cAMP dependent). Moreover, the effects of phorbol esters and 5-HT on spike duration were not additive, suggesting that they may share some common mechanisms. 3. The protein kinase inhibitor staurosporine suppressed both 5-HT-induced slowly developing spike broadening and, under certain conditions, facilitation of transmitter release. Staurosporine did not inhibit 5-HT-induced enhancement of excitability. The effectiveness of staurosporine on spike broadening was dependent on the time at which spike broadening was examined after application of 5-HT. Staurosporine appeared to have little effect on spike broadening 3 min after application of 5-HT, whereas it inhibited significantly 5-HT-induced spike broadening at later times. The staurosporine-insensitive component of 5-HT-induced spike broadening may be mediated by cAMP. 4. The results suggest that the activation of PKC plays a key role in components of both 5-HT-induced spike broadening and facilitation of synaptic transmission.(ABSTRACT TRUNCATED AT 250 WORDS)
Acoustic reflex frequency selectivity in single stapedius motoneurons of the cat
Authors: Kobler J. B. , Guinan J. J. , Vacher S. R. , Norris B. E.
Published: December 2017

1. The sound frequency selectivities of single stapedius motoneurons were investigated in ketamine anesthetized and in decerebrate cats by recording from axons in the small nerve fascicles entering the stapedius muscle. 2. Stapedius motoneuron tuning curves (TCs) were very broad, similar to the tuning of the overall acoustic reflexes as determined by electromyographic recordings. The lowest thresholds were usually for sound frequencies between 1 and 2 kHz, although many TCs also had a second sensitive region in the 6- to 12-kHz range. The broad tuning of stapedius motoneurons implies that inputs derived from different cochlear frequency regions (which are narrowly tuned) must converge at a point central to the stapedius motoneuron outputs, possibly at the motoneuron somata. 3. There were only small differences in tuning among the four previously described groups of stapedius motoneurons categorized by sensitivity to ipsilateral and contralateral sound. The gradation in high-frequency versus low-frequency sensitivity across motoneurons suggests there are not distinct subgroups of stapedius motoneurons, based on their TCs. 4. The thresholds and shapes of stapedius motoneuron TCs support the hypothesis that the stapedius acoustic reflex is triggered by summed activity of low-spontaneous-rate auditory nerve fibers with both low and high characteristic frequencies (CFs). Excitation of high-CF auditory nerve fibers by sound in their TC “tails” is probably an important factor in eliciting the reflex. 5. In general, the most sensitive frequency for stapedius motoneurons is higher than the frequency at which stapedius contractions produce the greatest attenuation of middle ear transmission. We argue that this is true because the main function of the stapedius acoustic reflex is to reduce the masking of responses to high-frequency sounds produced by low-frequency sounds.
Metabotropic glutamate receptor-mediated suppression of L-type calcium current in acutely isolated neocortical neurons
Authors: Sayer R. J. , Schwindt P. C. , Crill W. E.
Published: December 2017

1. The effects of metabotropic glutamate receptor (mGluR) stimulation on whole-cell Ca2+ currents were studied in pyramidal neurons isolated from the dorsal frontoparietal neocortex of rat. The selective mGluR agonist cis-(+/-)-1-aminocyclopentane-1,3-dicarboxylic acid [trans-ACPD (100 microM)] suppressed the peak high-threshold Ca2+ current by 21 +/- 1.7% (mean +/- SE) in 40 of 43 cells from 10- to 21-day-old rats. Consistent with previous findings for mGluR, glutamate, quisqualate, and ibotenate [but not alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)] reduced the Ca2+ currents, and the responses were not blocked by the ionotropic glutamate receptor antagonists 6-cyano-7-nitro-quinoxaline-2,3-dione (CNQX) and DL-2-amino-5-phosphonovaleric acid (APV). EC50S for Ca2+ current suppression were 29 nM for quisqualate, 2.3 microM for glutamate, and 13 microM for trans-ACPD. 2. The low-threshold Ca2+ current was not modulated by trans-ACPD. The component of the high-threshold CA2+ current suppressed by mGluR was determined by pharmacology; the responses were not affected by omega-conotoxin GVIA but were occluded by the dihydropyridine Ca2+ antagonist nifedipine. Ca2+ tail currents prolonged by the dihydropyridine Ca2+ agonist (+)-SDZ 202-79] were suppressed by mGluR stimulation in parallel with the peak current. These findings strongly suggest that L-type Ca2+ channels are modulated by mGluR. 3. In neurons dialyzed with 100 microM guanosine 5'-(gamma-thio)triphosphate (GTP-gamma-S), Ca2+ current suppression was elicited by the first application of trans-ACPD (in 5 of 6 cells), but not by subsequent applications. Responses in neurons dialyzed with 2 mM guanosine 5'-(beta-thio)diphosphate (GDP-beta-S) were significantly smaller than controls. The results are consistent with mGluR acting via linkage to a G protein. 4. The responses to mGluR agonists were smaller when the external Ca2+ was replaced by Ba2+, indicating that some part of the mechanism underlying the current suppression is Ca2+ dependent. Because mGluR stimulates phosphoinositide turnover and release of Ca2+ from intracellular stores in other types of neurons, the possibility of released Ca2+ mediating inactivation of Ca2+ channels was considered. However, the Ca2+ current suppression was not attenuated by strong intracellular Ca2+ buffering [20 mM bis-(o-aminophenoxy)-N,N,N',N'-tetraacetic acid (BAPTA)], by dialysis with 100 microM inositol-1,4,5-triphosphate (IP3), or by external application of 1 microM thapsigargin. 5. We conclude that in neocortical neurons, one action of mGluR is to suppress the component of high-threshold Ca2+ current conducted by L-type Ca2+ channels.(ABSTRACT TRUNCATED AT 400 WORDS)
Sensory processing and corollary discharge effects in the mormyromast regions of the mormyrid electrosensory lobe. I. Field potentials, cellular activity in associated structures
Authors: Bell C. C. , Grant K. , Serrier J.
Published: December 2017

1. This is the first of a series of papers on the electrosensory lobe and closely associated structures in electric fish of the family Mormyridae. The study describes the neuronal responses to sensory stimuli and to corollary discharge signals associated with the motor command that drives the electric organ discharge (EOD). The study is focused on the regions of the electrosensory lobe where primary afferent fibers from mormyromast electroreceptors terminate. 2. This first paper of the series describes the field potentials in the caudal lobe of the cerebellum and in the electrosensory lobe. It also describes the different types of unit activity in the caudal lobe of the cerebellum. Granule cells of the caudal lobe of the cerebellum provide the parallel fibers for most of the molecular layer of the electrosensory lobe. Determination of the input and responses of these cells is therefore an important part of the effort to understand the electrosensory lobe. 3. Corollary discharge field potentials evoked by the EOD motor command are very prominent in the caudal lobe of the cerebellum and in the electrosensory lobe. The potentials indicate that corollary discharge excitation affects first the granule cells of the caudal lobe and then, a few milliseconds later, the deeper cellular layers of the electrosensory lobe. The prominence and complexity of the field potentials indicate that corollary discharge signals have an important and varied role in the processing of electrosensory information by the mormyrid electrosensory lobe. 4. The field potentials evoked by electrosensory stimuli suggest that direct primary afferent excitation is limited to the granule and intermediate layers of the electrosensory lobe, as is indicated also by anatomic studies. 5. Proprioceptive units are the most common type of unit recorded in the granule cell region of the caudal lobe of the cerebellum (eminentia granularis posterior). These units have a regular discharge rate that changes tonically in response to slight bending of the trunk, bending of the tail, or bending of individual fins. Proprioceptive input will have a strong effect on the molecular layer of the electrosensory lobe and will thus modulate the responses of electrosensory lobe cells to electrosensory stimuli. Such proprioceptive input to the electrosensory lobe would allow the expected effects of body position changes to be accounted for in the processing of electrosensory information. 6. Units with stereotyped, short-latency corollary discharge bursts to the EOD motor command were the next most common type of unit in the eminentia granularis posterior. These corollary discharge units were not affected by sensory stimuli.(ABSTRACT TRUNCATED AT 400 WORDS)
Changes in motor responses induced by cerebellar stimulation during classical forelimb flexion conditioning in cat
Authors: Rispal-Padel L. , Meftah E. M.
Published: December 2017

1. The ability of somaesthetic sensory inputs to produce structural changes in the connectivities of the central nervous structures involved in motor activity was tested with an alpha type of classical conditioning in chronically prepared adult cats. Repetitive sensory stimulation was applied at constant intervals after the activation of the motor circuits originating in the neurons or efferent axons of the cerebellar nuclei. A conditional stimulation (CS) applied to interpositus neurons was consistently paired with an unconditional stimulation (UCS) applied to the dorsal skin of the forelimb extremity to induce associative sensorimotor conditioning. The sites at which the conditional and unconditional stimuli were applied set up a simplified sensorimotor circuit including pathways transmitting both these stimuli and others mediating the expression of the conditioned responses. 2. To test the changes resulting from the conditioning, electrodes were implanted into the various relay structures on the cerebellar efferent pathways (ventrolateral nucleus motor cortex). The forelimb motor responses elicited by stimulating these relay structures were recorded with a potentiometer placed at the elbow joint. The angular displacement (amplitude) and latency of the responses and the percentage response rates were systematically quantified throughout the conditioning procedure and at test sessions carried out after the daily conditioning routines. 3. It was observed that daily repetition of paired CS-UCS led to an increase in the response rates and amplitudes of the forelimb flexions, which already began to occur very slightly on the first 4 or 5 days in response to the alpha conditioning, whereas the CS when applied alone failed to produce any changes in this initial response. Likewise, after the acquisition phase, repeated presentation of either the CS alone or the CS preceded by the UCS led to the extinction of the conditioned response, thus indicating that the observed changes were of an associative nature and that they depended on interactions between the motor and sensory inputs occurring somewhere in the CNS. In fact, the effects of conditioning were not generalized, but involved only a circumscribed circuit originating in the cerebellar neurons stimulated by the CS, which were activated concomitantly with the sensory pathways. 4. The conditioned response amplitudes were enhanced by 2.5–3 times their initial value. This enhancement persisted at the end of acquisition or after several days of consolidation, even when the paired CS-UCS sessions were interrupted for a period of 15 days to 2 mo.(ABSTRACT TRUNCATED AT 400 WORDS)
Primate premotor cortex: dissociation of visuomotor from sensory signals
Authors: Wise S. P. , Di Pellegrino G. , Boussaoud D.
Published: December 2017

1. If we assume adequate control for attention, memory, and stimulus location, a bona fide sensory response would be unaffected by whether a visuospatial stimulus instructs (1) one limb movement versus another or (2) limb movement versus a shift in spatial attention or memory. Two behavioral methods tested whether apparently sensory responses in the monkey's premotor cortex are strictly that, or, alternatively, whether they reflect the action instructed by a stimulus. 2. When an identical stimulus leads to two different responses, phasic discharge after a visuospatial stimulus is significantly, often dramatically, affected by the response. Similarly, premotor cortex neurons discharge more after a stimulus instructs a limb movement than after the same stimulus instructs a shift in spatial attention or memory. Thus, for the majority of premotor cortex neurons, the hypothesis that phasic poststimulus activity modulation represents a sensory response can be rejected.
Intravenous morphine-induced activation of vagal afferents: peripheral, spinal, and CNS substrates mediating inhibition of spinal nociception and cardiovascular responses
Authors: Randich A. , Thurston C. L. , Ludwig P. S. , Robertson J. D. , Rasmussen C.
Published: December 2017

1. Intravenous administration of 1.0 mg/kg of morphine produces inhibition of the nociceptive tail-flick (TF) reflex, hypotension, and bradycardia in the pentobarbital-anesthetized rat. The present experiments examined peripheral, spinal, and supraspinal relays for inhibition of the TF reflex and cardiovascular responses produced by morphine (1.0 mg/kg iv) in the pentobarbital-anesthetized rat using 1) bilateral cervical vagotomy, 2) spinal cold block or mechanical lesions of the dorsolateral funiculi (DLFs), or 3) nonselective local anesthesia or soma-selective lesions of specific CNS regions. Intravenous morphine-induced inhibition of responses of unidentified, ascending, and spinothalamic tract (STT) lumbosacral spinal dorsal horn neurons to noxious heating of the hindpaw were also examined in intact and bilateral cervical vagotomized rats. 2. Bilateral cervical vagotomy significantly attenuated inhibition of the TF reflex and bradycardia produced by intravenous administration of morphine. Bilateral cervical vagogtomy changed the normal depressor response produced by morphine into a sustained pressor response. Inhibition of the TF reflex in intact rats was not due to changes in tail temperature. 3. Spinal cold block significantly attenuated inhibition of the TF reflex, the depressor response, and the bradycardia produced by intravenous administration of morphine. However, bilateral mechanical transections of the DLFs failed to significantly affect either inhibition of the TF reflex or cardiovascular responses produced by this dose of intravenous morphine. 4. Microinjection of either lidocaine or ibotenic acid into the nuclei tracti solitarii (NTS), rostromedial medulla (RMM), or ventrolateral pontine tegmentum (VLPT) attenuated morphine-induced inhibition of the TF reflex. Similar microinjections into either the periaqueductal gray (PAG) or the dorsolateral pons (DLP) failed to affect morphine-induced inhibition of the TF reflex. 5. Microinjection of either lidocaine or ibotenic acid into the NTS, RMM, VLPT, DLP, or rostral ventrolateral medulla (RVLM) attenuated the depressor response produced by morphine, although baseline arterial blood pressure (ABP) was affected by ibotenic acid microinjections in the DLP. In all these cases, the microinjections failed to reveal a sustained pressor response as was observed with bilateral cervical vagotomy. Similar microinjections into the PAG failed to affect the depressor response produced by morphine. 6. The lidocaine and ibotenic acid microinjection treatments also showed that the bradycardic response produced by morphine depends on the integrity of the NTS, RMM, RVLM, and possibly the DLP, but not the PAG or VLPT.(ABSTRACT TRUNCATED AT 400 WORDS)
Binaural interaction in the lateral superior olive: time difference sensitivity studied in mouse brain slice
Authors: Wu S. H. , Kelly J. B.
Published: December 2017

1. The sensitivity of lateral superior olive (LSO) neurons to interaural time differences was examined in an in vitro brain slice preparation. Brain slices, 400-500 microns, were taken through the superior olivary complex of C57 BL/6J mice and were maintained in an oxygenated saline solution for single-unit recording. Both extracellular and intracellular recordings were made with glass pipettes filled with 4 M potassium acetate. Responses were elicited by applying current pulses to the trapezoid body through bipolar stimulating electrodes located ipsilateral or contralateral to the olivary complex. Binaural interactions were studied by manipulating the timing and intensity of paired ipsilateral and contralateral pulses. 2. In extracellular recordings, stimulation of the ipsilateral trapezoid body usually elicited a single action potential, whereas stimulation of the contralateral trapezoid body failed to produce a spike response. Bilateral stimulation resulted in the complete suppression of the evoked spike, indicating the presence of a contralateral inhibitory effect. The degree of inhibition depended on the interpulse interval between ipsilateral and contralateral stimulation. With sufficiently large ipsilateral lead times, the probability of eliciting an extracellular spike was 1.0. As the interpulse interval was gradually shifted to reduce the ipsilateral lead time, the response probability precipitously dropped to 0.0. Most neurons could be completely suppressed by simultaneous stimulation. The dynamic range, defined as the range of interpulse intervals over which response probability changed from 0.9 to 0.1, was between 125 and 225 microseconds for most cells tested. 3. With increasing contralateral lead times, the extracellularly recorded spike was eventually released from inhibition.(ABSTRACT TRUNCATED AT 250 WORDS)
Calcium transients in cerebellar Purkinje neurons evoked by intracellular stimulation
Authors: Lev-Ram V. , Miyakawa H. , Lasser-Ross N. , Ross W. N.
Published: December 2017

1. Purkinje cells in thin slices from the guinea pig cerebellum were injected with fura-2 and high-speed sequences of fluorescence images from the cell body and entire dendritic tree were made while simultaneously recording somatic membrane potential during evoked and spontaneous electrical activity. The changes in fluorescence were interpreted in terms of changes in [Ca2+]i. 2. Individual calcium action potentials were usually accompanied by transient increases in [Ca2+]i all over the dendritic field. During evoked or spontaneous bursts of calcium spikes, [Ca2+]i increased more rapidly and to higher concentrations in fine dendrites than in thicker dendrites. At the end of a burst [Ca2+]i declined faster in thin dendrites than in thicker ones. These variations are most easily understood as deriving from the difference in surface-to-volume ratio of the two kinds of dendrites. 3. During bursts of calcium action potentials [Ca2+]i increases sometimes occurred only in individual dendritic branches, but always including the fine dendrites of that particular branch, showing that calcium action potentials can be regenerative in restrictive parts of the dendritic field without involving the soma or dendritic shaft. 4. Plateau or subthreshold potential changes evoked in the presence of tetrodotoxin (TTX) caused small, widespread increases in [Ca2+]i. The amplitude of these changes was much less than the increase corresponding to spike bursts. The distribution of these plateau Ca signals in thick and thin dendrites was similar to Ca spike-evoked signals, suggesting that the Ca conductances underlying these two potentials are the same or are distributed similarly in the dendrites. 5. Significant increases in [Ca2+]i in the soma were recorded during bursts of sodium-dependent action potentials in normal Ringer. Although much of this increase is due to calcium entry through calcium channels, some of this increase could be due to calcium entry through sodium channels.
Strong heat stimulation sensitizes the heat response as well as the bradykinin response of visceral polymodal receptors
Authors: Mizumura K. , Sato J. , Kumazawa T.
Published: December 2017

1. Hyperalgesia after thermal injury is a common phenomenon, but its mechanism is poorly understood. As a step toward understanding the mechanism for heat sensitization, we searched conditions that would induce sensitization consistently and studied changes in polymodal receptors in their responses to heat (45 and 48 degrees C) and to bradykinin. Experiments were conducted in vitro, with the use of testis-superior spermatic nerve preparations excised from anesthetized dogs. 2. Stimulation at 55 degrees C for 30 s induced clear augmentation of the responses to stimulations at 45 and 48 degrees C when tested within 10 min in 22 out of 24 testicular polymodal units. In the remaining two units, weak or delayed augmenting tendencies were observed. The response to stimulation at 45 degrees C increased from 0.28 +/- 0.08 to 2.99 +/- 0.46 (SE) imp/s, whereas at 48 degrees C it increased from 1.08 +/- 0.16 to 4.60 +/- 0.63 imp/s (P < 0.001, n = 24). A low-level ongoing discharge appeared in about one-half of the units studied. 3. Despite frequent rinsing of the receptive field, augmentation of the heat response observed after stimulation at 55 degrees C continued for up to approximately 3 h. 4. The response to bradykinin (94 nM) was also potentiated: the net mean discharge rate (NMDR) during a 1-min application period of bradykinin as well as the total number of impulses induced by one bradykinin application significantly increased from 0.91 +/- 0.27 to 1.97 +/- 0.32 imp/s and from 213.9 +/- 42.3 to 433.5 +/- 58.7 impulses, respectively (P < 0.001, n = 15).(ABSTRACT TRUNCATED AT 250 WORDS)
Role of metabotropic glutamate (ACPD) receptors at the parallel fiber-Purkinje cell synapse
Authors: Glaum S. R. , Slater N. T. , Rossi D. J. , Miller R. J.
Published: December 2017

1. The role of metabotropic glutamate receptors at the parallel fiber (PF)-Purkinje cell synapse in cerebellum was studied by examining the actions of the active stereoisomer (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid [1S,3R-ACPD (25-50 microM)] on fura-2-loaded, patch-clamped rat Purkinje cells in thin slices. 2. The bath application of 1S,3R-ACPD evoked a direct post-synaptic depolarization that readily desensitized during prolonged (> 1 min) applications of the drug. This depolarizing response to 1S,3R-ACPD differed from the slow depolarization to 1S,3R-ACPD observed in cortical neurons mediated via closure of potassium channels in that it was not associated with an obvious change in membrane conductance and was not blocked by external barium. Similarly, slow inward rectifier currents were not affected during the 1S,3R-ACPD-induced depolarization. 3. The direct depolarization induced by 1S,3R-ACPD was not mediated by N-methyl-D-aspartate (NMDA) or (RS)-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid kainate (AMPA)-KA excitatory amino acid (EAA) receptor subtypes, because the response was not blocked in the presence of antagonists of these receptors. 4. The EAA antagonist L-2-amino-3-phosphonopropionic acid, which blocks 1S,3R-ACPD-induced inositide synthesis in other cell types, had no effect on the depolarizing response. 5. Fura-2 measurements of somatic [Ca2+]i revealed that [Ca2+]i was not elevated during the 1S,3R-ACPD-induced depolarization unless the cell fired calcium-dependent action potentials. 6. In addition to the direct depolarization induced by 1S,3R-ACPD, the amplitude of PF-evoked excitatory postsynaptic potentials (EPSPs) was profoundly and reversibly reduced. This effect was observed in all cells regardless of whether a direct depolarization was produced by 1S,3R-ACPD. This reduction of the PF EPSP generally preceded the onset of depolarizing responses, did not desensitize during prolonged applications of 1S,3R-ACPD, and was reversible. 7. The reversible reduction of the PF EPSP by 1S,3R-ACPD was not related to a postsynaptic blocking action of the drug, because responses of Purkinje cells to AMPA, an agonist of the EAA receptor subtype mediating the EPSP, were reversibly potentiated in the presence of 1S,3R-ACPD. 8. The nitric oxide synthesis promoter sodium nitroprusside (1-3 nM) had no effect on the amplitude of PF EPSP or the membrane properties of Purkinje cells.(ABSTRACT TRUNCATED AT 400 WORDS)
Saccade-vergence interactions in humans
Authors: Zee D. S. , Fitzgibbon E. J. , Optican L. M.
Published: December 2017

1. We recorded eye movements in four normal human subjects during refixations between targets calling for various combinations of saccades and vergence. We confirmed and extended prior observations of 1) transient changes in horizontal ocular alignment during both pure horizontal saccades (relative divergence followed by relative convergence) and pure vertical saccades (usually divergence for upward and convergence for downward saccades); 2) occasional, high-frequency (20-25 Hz), conjugate oscillations along the axis orthogonal to the main saccade; and 3) the speeding up of horizontal vergence by both horizontal and vertical saccades. 2. To interpret these findings, we developed a hypothesis for the generation of vergence to step changes in target depth, both with and without associated saccades. The essential features of this hypothesis are 1) the transient changes in horizontal ocular alignment during pure horizontal saccades reflect asymmetries in the mechanical properties of the lateral and medial rectus muscles causing adduction to lag abduction; 2) pure vergence movements in response to step changes in target depth are generated by a neural network that uses a desired change in vergence position as its input command and instantaneous vergence motor error (the difference between the desired change and the actual change in vergence) to drive vergence premoter neurons; and 3) the facilitation of horizontal vergence by saccades arises from nonlinear interactions in central premotor circuits. 3. The hypothetical network for generating pure vergence to step changes in target depth is analogous in structure to the local feedback model for the generation of saccades and has the same conceptual appeal. With the assumption of a single nonlinearity describing the relationship between a vergence motor error signal and the output of the neurons that generate promoter vergence velocity commands, this model generates pure vergence movements with peak velocity-amplitude relationships and trajectories that closely match those of experimental data. 4. Several types of models are proposed for the central, nonlinear interaction that occurs when saccades and vergence are combined. Common to all models is the idea that omnidirectional pause neurons (OPN), which are thought to gate activity for saccade burst neurons, also gate activity for saccade-related vergence. In one model we hypothesize the existence of a separate class of saccade-related vergence burst neurons, which generate premotor horizontal vergence commands but only during saccades. In a second model we hypothesize separate right eye and left eye saccadic burst neurons that receive not only conjugate, but also equal but oppositely directed vergence error signals.(ABSTRACT TRUNCATED AT 400 WORDS)