bluuebunny/crossref_metadata_2025 huggingface dataset:
Calcium currents in turtle retinal ganglion cells. II. Dopamine modulation via a cyclic AMP-dependent mechanism
Authors: Liu Y. , Lasater E. M.
Published: December 2017

1. Voltage-activated calcium currents participate in shaping the firing pattern of neurons. Calcium currents also have a role in signal transduction. In the retina, little is known of the regulation of calcium entry into neurons via voltage-activated channels. In the present series of experiments we used standard whole cell and perforated patch clamp techniques to study the ability of the neurotransmitter dopamine (DA) to modulate voltage-dependent calcium currents in isolated turtle retinal ganglion cells. 2. Two types of calcium current have been described in these cells, one transient and the other sustained. Here we focused our studies primarily on the sustained current (ICa). Exogenous DA reduced ICa in some cells (59%), facilitated ICa in others (17%), or had no effect on the remainder (24%). Regardless of the action of DA, there was no effect on the voltage dependence of ICa. In addition, the effects were all reversible. The average magnitude of decrease was 43%, whereas that of increase was 75%. 3. The application of a specific D1 receptor agonist, SKF38393, mimicked the effect of DA. This was also true for a membrane permeable cyclic AMP (cAMP) analogue (8-CPT-cAMP). Inhibition of protein kinase A (PKA) activity by a specific inhibitor, IP20-amide, injected into cells prevented the modulatory effects of DA on ICa. 4. Immunocytochemical studies demonstrated that DA stimulation of the retina significantly increased the level of cAMP immunoreactivity in peripheral ganglion cells, whereas those cells in central retina were less affected. Forskolin induced a general elevation of cytoplasmic cAMP staining in all ganglion cells. 5. Current clamp experiments were carried out to determine the role of the calcium currents in action potential generation. Both the sustained and transient currents participated in the shaping of current-induced firing patterns of isolated cells. Depolarizing current-induced spiking of ganglion cells was found to be highly modified by dopamine. 6. These results support the notion that endogenous DA modulates the conductance of voltage-dependent calcium channels in turtle retinal ganglion cells and that this modulation is mediated by a D1 dopamine receptor-cAMP-PKA pathway. The direct result of this modulation is an alteration in the signaling properties of certain cells.
Calcium imaging reveals nicotinic acetylcholine receptors on cultured mushroom body neurons
Authors: Bicker G. , Kreissl S.
Published: December 2017

1. We used fluorescence imaging with the visible wavelength indicator fluo-3 to investigate the calcium responses to cholinergic ligands of honeybee Kenyon cells in primary culture. 2. Application of acetylcholine (ACh) or nicotine, but not pilocarpine, promoted a calcium influx into the cell body and neurites. The increase in intracellular calcium after ACh stimulation was blocked by alpha-bungarotoxin. These results support previous histochemical studies that suggested the expression of nicotinic cholinergic receptors on Kenyon cells. 3. After depolarization with high K+ solution fluorescence increased in the somata and neurites, which indicates the presence of voltage-gated Ca2+ channels in Kenyon cell membranes.
Electrophysiological evidence for presynaptic nicotinic receptors in the avian ventral lateral geniculate nucleus
Authors: McMahon L. L. , Yoon K. W. , Chiappinelli V. A.
Published: December 2017

1. Whole-cell patch-clamp recording in embryonic chick brain slices was used to examine the effect of nicotinic receptor activation on synaptic activity in neurons of the ventral lateral geniculate nucleus (LGNv). In LGNv neurons with input resistances < 250 M omega, bath perfusion of the nicotinic agonist, carbachol (10-30 microM), in the presence of 0.5-1.0 microM tetrodotoxin (TTX) and 1.0 microM atropine, produced a dramatic increase in the frequency of spontaneous postsynaptic currents (n = 8/8), while eliciting little or no direct postsynaptic response. The nicotinic antagonist, dihydro-beta-erythroidine (DH beta E; 30-100 microM) had no effect on basal synaptic currents, but blocked the carbachol-induced enhancement of spontaneous currents, demonstrating that activation of nicotinic receptors is responsible for this effect. 2. The gamma-aminobutyric acid A (GABAA) receptor antagonist, bicuculline (10-20 microM), blocked the basal spontaneous synaptic currents (n = 4) as well as the carbachol-induced enhancement of these events (n = 3), indicating that these currents are likely to be GABAergic inhibitory postsynaptic currents (IPSCs). 3. Because the nicotinic agonist-induced increase in IPSC frequency occurred during blockade of synaptic transmission with TTX, the enhancement of synaptic activity is not dependent upon action potential propagation. This is in marked contrast to our results in chick lateral spiriform neurons in which nicotinic agonist-induced increases in spontaneous GABAergic IPSCs were completely abolished in the presence of TTX. The data indicate that the nicotinic receptors mediating the increase in IPSC frequency in the LGNv are likely to be located directly on presynaptic nerve terminals.
Mechanism of early anoxia-induced suppression of the GABAA-mediated inhibitory postsynaptic current
Authors: Katchman A. N. , Vicini S. , Hershkowitz N.
Published: December 2017

1. We investigated the mechanism of hypoxia-induced depression of gamma-aminobutyric acid-A (GABAA)-mediated inhibitory postsynaptic currents (IPSCs) in CA1 neurons of hippocampal slices from 21- to 28-day-old rats. Cells were examined by whole-cell patch-clamp recording and hypoxia was induced by switching perfusion of the slice from oxygenated artificial cerebral spinal fluid (ACSF) to ACSF saturated with 95% N2-5% CO2. 2. Synaptic responses evoked by stimulation of the Schaffer collateral-commissural projection at a fixed holding potential (VH = -60 mV) during anoxia revealed that the IPSC appeared more sensitive than the excitatory postsynaptic current to anoxia-induced depression. All subsequent studies examined the GABAA-mediated IPSC synaptic responses in isolation by direct stimulation of GABA interneurons in the stratum radiatum in the presence of extracellular 3-(2-carboxypiperazine-4-yl)propyl-1-phosphonic acid (CPP) (20 microM) and 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) (50 microM) to block glutamatergic currents and intracellular QX-314 (lidocaine N-ethyl bromide, 1 mM) to block GABAB-mediated currents. When studied in this manner (VH = -60 mV) the GABAA-mediated IPSC appeared to change from an outward to inward current after exposure to anoxia. 3. The current-voltage relationship of GABAA-mediated IPSCs revealed that these changes resulted from a positive shift in the IPSC reversal potential without a significant change in the conductance. Thus under patch clamp apparent IPSC inhibition may result from a decrease in the extracellular concentration of chloride ions. Similar findings were observed with micropipettes that contained high intracellular chloride concentrations. 4. Miniature spontaneous IPSCs were examined in the presence of tetrodotoxin (1 microM) with micropipettes containing high intracellular chloride concentrations. The miniature IPSCs (mIPSCs) appeared as spontaneous transient inward currents. Consistent with an anoxia-induced decrease in extracellular chloride, the mean amplitude of the mIPSCs increased after the onset of anoxia. A significant decrease in rise and decay time was also noted during anoxia. The frequency of the mIPSCs also increased by approximately 300%. 5. The resting input resistance of the cells was examined by measuring the current resulting from a 20-mV hyperpolarizing pulse. A significant reduction in resistance was observed 2 min after the onset of anoxia. This still occurred, although to a lesser degree, in the presence of glutamatergic blockers (20 microM CPP plus 50 microM CNQX). In the presence of both GABAergic (picrotoxin, 100 microM) and glutamatergic blockers no significant reduction in resting input resistance was apparent after 2 min of anoxia.(ABSTRACT TRUNCATED AT 400 WORDS)
Ca(2+)-dependent non-NMDA receptor-mediated synaptic currents in ischemic CA1 hippocampal neurons
Authors: Tsubokawa H. , Oguro K. , Masuzawa T. , Kawai N.
Published: December 2017

1. The changes in excitatory postsynaptic currents (EPSCs) after transient cerebral ischemia were studied using whole-cell recording from CA1 pyramidal neurons in gerbils. In 64% (18 of 28) neurons recorded 1.5-3 days after ischemia, EPSCs showed a markedly slowed time course that was never seen in normal control neurons. 2. The slow EPSCs were not affected by an N-methyl-D-aspartate (NMDA) receptor antagonist [DL-2-aminophosphonovalerate (APV); 100 microM] but were abolished by a non-NMDA receptor antagonist [6-cyano-7-nitroquinoxaline-2,3-dione (CNQX); 10 microM], indicating that the slow EPSCs were mostly composed of non-NMDA current. 3. The slow non-NMDA EPSCs had rise times ranging from 1.2 to 7.3 ms and decay time constants between 11.5 and 56.3 ms. In normal neurons the rise time of the non-NMDA component of EPSCs ranged from 1.6 to 7.5 ms and the decay time constants ranged from 4.9 to 27.3 ms. 4. The reversal potential of the slow EPSCs in ischemic neurons was not changed by replacing 50% of the NaCl in the external solution with sodium isethionate. Bath application of 4-acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic acid (SITS; 100 microM) had no effect on the slow EPSCs. Therefore Cl- current is not responsible for the slow EPSCs. 5. When external Ca2+ concentration was reduced to half of control, the decay time constant of the slow EPSCs decreased to 50 +/- 25%, mean +/- SD. In addition, bath application of a cell-permeable Ca2+ chelator, 1,2-bis(o-aminophenoxy)ethane-N,N,-N',N'-tetraacetyl,tetr aacetoxymethyl ester(BAPTA-AM), reduced the decay time constant.(ABSTRACT TRUNCATED AT 250 WORDS)
Defense reaction in the pond snail Planorbis corneus. I. Activity of the shell-moving and respiratory systems
Authors: Arshavsky Y. I. , Deliagina T. G. , Okshtein I. L. , Orlovsky G. N. , Panchin Y. V. , Popova L. B.
Published: December 2017

1. In the intact pond snail Planorbis corneus, tactile or electrical stimulation of the skin evoked a biphasic general defense reaction. A weak stimulation evoked only the first phase of the reaction, represented as a fast pulling of the shell towards the head. With stronger stimulation, this phase was followed by the second phase that was comprised of three components: detachment from the substrate, slow retraction of the body into the shell, and letting out of air from the lung through the pneumostome. 2. About 70 motor neurons (MNs) of the columellar muscle have been revealed in different ganglia by means of their cobalt back-filling through the cut columellar nerve. A complicated pattern of electrical coupling was found for different groups of MNs. Excitation of individual MNs, evoked by current injection, resulted in contraction of the columellar muscle (CNS-columellar muscle preparation). The strongest contraction was evoked by the cerebral MNs; fast small contraction by the parietal MNs; and slow, long-latency contraction, by the pedal MNs. 3. In the same preparation, electrical stimulation of the cutaneous (lip) nerve evoked biphasic contraction of the columellar muscle (a first phase lasting approximately 3 s, and a second phase of up to 1 min). The temporal pattern of this response was similar to that of the defense reaction in the intact animal. A weak stimulation evoked only the first phases of the reaction, while a stronger stimulation evoked both phases. The amplitude of both the first and the second phase was graded with the strength of stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)
Regulation of cutaneous C-fiber heat nociceptors by nerve growth factor in the developing rat
Authors: Lewin G. R. , Mendell L. M.
Published: December 2017

1. Previous work has indicated that nerve growth factor (NGF) is an important factor for the development of nociceptive A-delta fibers. Here we asked if the availability of NGF during the first 2 wk of development can influence the phenotypic development of unmyelinated afferent C-fibers. 2. To do this, we treated newborn rats with antibodies to NGF from postnatal day (PND) 2-14, a treatment known not to lead to cell death, or with exogenous NGF (PND 0-14). Untreated litter mates served as controls. When the animals were mature (5-20 wk later), they were anesthetized (urethan, 1.25 g/kg ip) and single-unit recordings were made from sural nerve C-fibers in dorsal root filaments. To obtain an unbiased estimate of the physiological types present, an electrocutaneous search technique was employed to isolate the location of the putative receptive field of the C-fiber being studied within the sural nerve territory. This technique enabled us to acquire a sample of C-fibers that was unbiased by natural search stimuli which are often damaging to skin. 3. We found that the proportion of C-fibers that could be driven by noxious heat and mechanical stimuli (C-mechanoheat fibers, C-MH) was reduced from 28% (11/40 fibers) of the sample in controls to 10% (3/31 fibers) in anti-NGF treated animals. The C-MH fibers appeared to have been replaced by a novel type of pressure receptor with an unusually low mechanical threshold (mean 0.86 +/- 0.58 compared with 13.0 +/- 8.3 g for control mechanonociceptors).(ABSTRACT TRUNCATED AT 250 WORDS)
Spinothalamic and spinohypothalamic tract neurons in the cervical enlargement of rats. I. Locations of antidromically identified axons in the thalamus and hypothalamus
Authors: Dado R. J. , Katter J. T. , Giesler G. J.
Published: December 2017

1. Seventy-seven neurons in the cervical enlargement of rats anesthetized with urethan were initially antidromically activated using currents < or = 30 microA from the contralateral posterior thalamus. A goal of these experiments was to determine the course of physiologically characterized spinal axons within the diencephalon. Therefore, in 38 cases, additional antidromic mapping was done throughout the mediolateral extent of the diencephalon at multiple anterior-posterior planes. 2. Electrolytic lesions marking the recording sites were recovered for 71 neurons. Thirty-one were located in the superficial dorsal horn (SDH); 39 were in nucleus proprius or the lateral reticulated area of the deep dorsal horn (DDH), and one was in the ventral horn. 3. Eight of 38 (21%) neurons that were tested for more anterior projections could only be antidromically activated with currents < or = 30 microA from sites in the contralateral posterior thalamus. Such neurons are referred to as spinothalamic tract (STT) neurons. Lesions marking the lowest threshold points for antidromic activation were located in or near the posterior thalamic group (Po). At more anterior levels, considerably higher currents were required for antidromic activation or it was not possible to activate the neurons with currents up to 500 microA. Four of these neurons were physiologically characterized and each responded preferentially to noxious mechanical stimuli (wide dynamic range, WDR). Each of the three neurons that were tested responded to noxious heat stimuli. These findings confirm anatomic studies that have shown that a number of STT axons terminate in Po and suggest that such axons that originate in the cervical enlargement carry nociceptive input from the upper extremity. 4. In 15 cases, electrode penetrations were made systematically throughout much of the contralateral ventrobasal complex (VbC). In 17 cases, penetrations were made throughout the intralaminar nuclei contralaterally, including the central lateral nucleus (CL). Surprisingly, only one of the examined axons was antidromically activated with low currents from CL and one from VbC, although both of these nuclei are known to receive sizeable inputs from the STT. 5. Many of the axons (27 of the 38 tested, 71%) that were initially antidromically activated from the contralateral posterior thalamus could also be antidromically activated with low currents (< or = 30 microA) and at increased latencies from sites located anteriorly in the contralateral hypothalamus. Such neurons are referred to as spinothalamic tract/spinohypothalamic tract (STT/SHT) neurons.(ABSTRACT TRUNCATED AT 400 WORDS)
Responses of single hamster parabrachial neurons to binary taste mixtures of NaCl with sucrose or QHCl
Authors: Vogt M. B. , Smith D. V.
Published: December 2017

1. Although human psychophysical responses to taste mixtures have been investigated extensively, there have been few reports on the neurophysiological coding of taste mixtures in the mammalian gustatory system. In recent studies we have investigated the responses of single third-order neurons in the hamster parabrachial nucleus (PbN) to anterior tongue stimulation with binary mixtures of heterogenous taste stimuli including sucrose+QHCl, sucrose+citric acid, and NaCl+citric acid. Some of these stimulus combinations evoked mixture suppression, or response frequencies that were less than that evoked by the more effective component (MEC) presented alone, which is analogous to the mixture suppression reported in human psychophysical studies of similar taste mixtures. In the current report we extend our investigation to include NaCl+QHCl and NaCl+sucrose mixtures. 2. The action potentials of single PbN neurons were recorded extracellularly. Four concentrations of each stimulus were employed: NaCl and sucrose at 0.001, 0.01, 0.1, and 1.0 M; QHCl at 0.00032, 0.0032, 0.032, and 0.1 M. All stimuli were tested alone and in mixture; the NaCl+sucrose and NaCl+QHCl mixtures were formed by pairing the four concentrations of each stimulus with the strongest concentration of the other stimulus. 3. For both NaCl+sucrose and NaCl+QHCl mixtures, the response frequencies evoked by the mixtures did not differ from those evoked by the MEC presented alone, whether averaged across all neurons or across subgroups of NaCl- or sucrose-best cells. Furthermore, the across-neuron patterns (ANPs) of mixture responses were similar to those of the MECs.(ABSTRACT TRUNCATED AT 250 WORDS)
A control strategy for the execution of explosive movements from varying starting positions
Authors: Van Soest A. J. , Bobbert M. F. , Van Ingen Schenau G. J.
Published: December 2017

1. Humans can execute explosive movements such as jumping and hitting an object irrespective of the starting position from which these movements have to be initiated; in fact, variability of kinematic parameters has been shown to decrease in the course of the movement. 2. We address the question of whether it is necessary to adapt the stimulation pattern of the muscles to such variations in starting position or whether the stabilizing effect of intrinsic muscle properties is such that one single muscle stimulation pattern might be used for a wide range of starting positions. 3. Specifically, we address this question for maximum-height human vertical squat jumping, using an approach based on mathematical modeling and computer simulation. The stimulation pattern of the muscles is the input of the model and the resulting movement is the output. 4. The optimal stimulation pattern for a starting position in the middle of the range of starting positions considered does not lead to adequate performance for other starting positions in that range. 5. However, a muscle stimulation pattern can be found that does result in close to optimal achievement for a wide range of starting positions. This muscle stimulation pattern, which is not optimal for any specific starting position, may be considered as "control that works" as opposed to "optimal control." 6. The latter muscle stimulation pattern also leads to adequate behavior for "new" starting positions both within and outside the range considered.
Intracellular characterization of identified sensory cells in a new spider mechanoreceptor preparation
Authors: Seyfarth E. A. , French A. S.
Published: December 2017

1. We have developed an isolated mechanoreceptor-organ preparation in which the intact sensory structures are available for mechanical stimulation and electrical recording. The anterior lyriform slit sense organ on the patella of the spider, Cupiennius salei Keys., consists of seven or eight cuticular slits, each innervated by a pair of large bipolar sensory neurons. The neurons are fusiform, and the largest somata are < or = 120 microns long. The innervation of the organ was characterized by light microscopy of neurons backfilled with neuronal tracers. Intracellular recording was used to measure the passive and active electrical properties of the neurons, in several cases followed by identification with Lucifer yellow injection. Both neurons of each pair from one slit responded with action potentials to depolarization by a step current injection. Approximately half of the sensory neurons adapted very rapidly and generated only one or two action potentials in response to a sustained depolarizing step, while a second group produced a burst of action potentials that adapted to silence in approximately 1 s or less. Recordings from identified neuron pairs indicated that each pair consists of one rapidly adapting and one bursting neuron. Measurements of cell membrane impedances and time constants produced estimates of neuronal size that agreed with the morphological measurements. This new preparation offers the possibility of characterizing the mechanisms underlying transduction and adaptation in primary mechanosensory neurons.
Activity of inferior temporal neurons during orientation discrimination with successively presented gratings
Authors: Vogels R. , Orban G. A.
Published: December 2017

1. We recorded from inferior temporal (IT) cells in three monkeys while they performed an orientation discrimination task with successively presented gratings. Histological reconstruction of two monkey brains indicated that most recordings were from TE3. The task was exactly the same as the one used in a previous V1 study, allowing direct comparison. 2. One quarter of IT cells were responsive to the grating. Response strength and variability of the cells excited by the grating (n = 341) were similar to those in V1, whereas response latency was on average 40 ms longer than in V1. 3. In one third of the responsive cells orientation had a significant effect. Sensitivity for orientation was captured by the orientation sensitivity index, which ranged from 0 to 0.95 with a median of 0.23. Orientation sensitivity of IT cells was on average much less than that of V1 cells. More cells preferred horizontal and vertical than oblique orientations. 4. The differences in responsiveness and orientation sensitivity among individual animals could be accounted for by the anterior/posterior difference in recording position. 5. Task-related behavioral effects were examined in 283 cells that were responsive to the visual stimuli. Order effects were examined in "same" trials and occurred in half of the IT cells in each of the three monkeys. In these cells there was on average a threefold difference in response between the first stimulus (S1) and the second stimulus in same trials (S2same). In two monkeys the average response to S2same was less than that to S1, whereas in the third monkey the average response to S1 was smaller than that to S2same. 6. IT cells also exhibited same/different effects, whereby response to a physically identical second stimulus differed between same and "different" trials. Generally cells responded more to the second stimulus in different trials than to S2same but the opposite also occurred. For a subset of these cells we could show that the correct/error type of the trial had no effect and that the response occurred before the saccadic response. 7. These context effects were modulations of the gain of the orientation tuning curves for the different types of responses. The tuning for orientation of these different responses was similar. 8. One third of the responsive IT cells exhibited an increased activity in the interstimulus interval (ISI), fitting the definition of delay cells. This activity was maintained when the ISI was lengthened from 300 to 800 ms. The orientation tuning of this response was similar to that for S1 responses.(ABSTRACT TRUNCATED AT 400 WORDS)
Effects of chronic spinalization on ankle extensor motoneurons. III. Composite Ia EPSPs in motoneurons separated into motor unit types
Authors: Hochman S. , McCrea D. A.
Published: December 2017

1. In this paper we continue an examination of changes in composite Ia excitatory postsynaptic potentials (EPSPs) in ankle extensor motoneurons after 6-wk (L1-L2) spinal cordotomy. The ratio of rheobase to input resistance was used to divide motoneurons into three groups approximating fast-fatigable (FF), fast fatigue-resistant (FR), and slow (S) motor units in barbiturate-anesthetized cats. Homonymous monosynaptic Ia EPSPs evoked by low-strength [1.2 times threshold (T)] electrical stimulation and heteronymous EPSPs evoked by 2T stimulation were compared between groups of motoneurons in unlesioned and chronic spinal preparations. 2. The distribution of motor unit types of triceps surae and plantaris (PL) motoneurons according to the present classification scheme agrees well with that obtained elsewhere using mechanical typing. Chronic spinalization resulted in an increased proportion of type FF motoneurons in PL and type FR motoneurons in lateral gastrocnemius (LG) motoneurons. There was a numeric but insignificant increase in the proportion of fast medial gastrocnemius motor units. 3. Membrane time constant (tau m) and estimated total cell capacitance were significantly reduced in FF and S motoneurons in chronic spinal preparations. FF motoneurons from chronic spinal animals also had a reduced afterhyperpolarization duration. Mean values of membrane electrical properties in FR motoneurons were unaltered after spinalization. 4. Homonymous Ia EPSP changes after chronic spinalization occurred preferentially in type FR and S motor units. Amplitudes increased 69% in type FR and 38% type S motor units but were unchanged in type FF units. Furthermore, the amplitudes of heteronymous Ia EPSPs in type FF and S units in the chronic spinal preparation were almost double those in unlesioned preparations. 5. Homonymous EPSP 10-90% rise times decreased 25% in type FR motor units and 15% in type S motor units and were unchanged in type FF motor units. Homonymous EPSP half-width decreased in all three motoneuron groups. Normalization of EPSP rise time and half-width to tau m reduced the difference between EPSP shape indexes in unlesioned and chronic spinal preparations in type FF and S motoneurons but less so in type FR motoneurons. Normalized EPSP shape indexes in some type FR units were shorter after chronic spinalization than any in unlesioned preparations. 6. The increased amplitude and decreased rise time of Ia EPSPs in type FR motoneurons after spinalization occurred without changes in the electrical properties of type FR motor units.(ABSTRACT TRUNCATED AT 400 WORDS)
Delayed depolarization and slow sodium currents in cutaneous afferents
Authors: Honmou O. , Utzschneider D. A. , Rizzo M. A. , Bowe C. M. , Waxman S. G. , Kocsis J. D.
Published: December 2017

1. Intraaxonal recordings were obtained in vitro from the sural nerve (SN), the muscle branch of the anterior tibial nerve (ATN), or the deafferented ATN (dATN) in 5- to 7-wk-old rats. Whole-nerve sucrose gap recordings were obtained from the SN and the ATN. This allowed study of cutaneous (SN), mixed motor and muscle afferent (ATN), and isolated muscle afferent (dATN) axons. 2. Application of the potassium channel blocking agent 4-aminopyridine (4-AP) to ATN or dATN resulted in a slight prolongation of the action potential. In contrast, a distinct delayed depolarization followed the axonal action potential in cutaneous afferents (SN) exposed to 4-AP. The delayed depolarization could be induced by a single whole-nerve stimulus or by injection of constant-current depolarizing pulses into individual axons. The delayed depolarization often gave rise to bursts of action potentials and was followed by a prominent afterhyperpolarization (AHP). 3. In paired-pulse experiments on single SN axons, the recovery time (half-amplitude of the action potential) was 3.06 +/- 1.82 (SE) ms (n = 12). After exposure to 4-AP the recovery time of the delayed depolarization was considerably longer (half-recovery time: 99.0 +/- 28.3 ms; n = 15) than that of the action potential (18.8 +/- 9.1 ms; n = 16). 4. Application of tetraethylammonium (TEA) to cutaneous or muscle afferents alone had little effect on single action potential waveform. However, TEA reduced the amplitude of the AHP elicited by a single stimulus in cutaneous afferent axons after exposure to 4-AP and resulted in repetitive spike discharge. 5. The delayed depolarization and spike burst activity induced by 4-AP in SN was present in Ca(2+)-free solutions containing 1 mM ethylene glycol-bis (beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid and was not blocked by Cd2+ (1.0 mM). 6. We obtained whole-cell patch-clamp recordings to study Na+ currents from either randomly selected dorsal root ganglion neurons or cutaneous afferent neurons identified by retrograde labeling with Fluoro-Gold. The majority of the randomly selected neurons had a singular kinetically fast Na+ current. In contrast, no identified cutaneous afferent neurons had a singular fast Na+ current. Rather, they had a combination of kinetically separable fast and slow currents or a singular relatively slow Na+ current.(ABSTRACT TRUNCATED AT 400 WORDS)
The antidromic compound action potential of the auditory nerve
Authors: Brown M. C.
Published: December 2017

1. The antidromic compound action potential (ACAP) of the auditory nerve was evoked by shocks to the auditory nerve root and recorded at the round window of the cochlea in anesthetized guinea pigs. The goal of this study was to determine the characteristics of the ACAP and compare these characteristics with those of the orthodromic, sound-evoked compound action potential (CAP). 2. The ACAP consists of an initial complex of a positive peak (p1) followed by a negative peak (n1). In contrast, the CAP consists of a negative peak (N1) followed by a positive peak (P1). These differences in waveform are likely due to the differences in conduction direction, antidromic for the ACAP vs. orthodromic for the CAP. 3. After the initial complex, the ACAP has a second complex of peaks (p2, n2) at a latency of approximately 1 ms; this complex is much smaller in amplitude than the initial complex (p1, n1). It is likely that the initial ACAP complex reflects firing of auditory-nerve fibers whereas the second complex reflects firing of neurons further centrally, perhaps in the cochlear nucleus, that are activated by orthodromic firing of auditory-nerve fibers. 4. Experiments with shock pairs are consistent with the idea that for auditory nerve fibers, the absolute refractory period is < 0.5 ms, and the relative refractory period is between 0.5 and at least 5 ms. 5. Experiments with click-shock pairs indicate that a shock interferes with the response to a click when the click and shock are given at about the same time.(ABSTRACT TRUNCATED AT 250 WORDS)
Compartmental modeling of rat macular primary afferents from three-dimensional reconstructions of transmission electron micrographs of serial sections
Authors: Chimento T. C. , Doshay D. G. , Ross M. D.
Published: December 2017

1. We cut serial sections through the medial part of the rat vestibular macula for transmission electron microscopic (TEM) examination, computer-assisted three-dimensional (3-D) reconstruction, and compartmental modeling. The ultrastructural research showed that many primary vestibular neurons have an unmyelinated segment, often branched, that extends between the heminode [putative site of the spike initiation zone (SIZ)] and the expanded terminal(s) (calyx, calyces). These segments, termed the neuron branches, and the calyces frequently have spinelike processes of various dimensions that morphologically are afferent, efferent, or reciprocal to other macular neural elements. The purpose of this research was to determine whether morphometric data obtained ultrastructurally were essential to compartmental models [i.e., they influenced action potential (AP) generation, latency, or amplitude] or whether afferent parts could be collapsed into more simple units without markedly affecting results. We used the compartmental modeling program NEURON for this research. 2. In the first set of simulations we studied the relative importance of small variations in process morphology on distant depolarization. A process was placed midway along an isolated piece of a passive neuron branch. The dimensions of the four processes corresponded to actual processes in the serial sections. A synapse, placed on the head of each process, was activated and depolarization was recorded at the end of the neuron branch. When we used 5 nS synaptic conductance, depolarization varied by 3 mV. In a systematic study over a representative range of stem dimensions, depolarization varied by 15.7 mV. Smaller conductances produced smaller effects. Increasing membrane resistivity from 5,000 to 50,000 omega cm2 had no significant effect. 3. In a second series of simulations, using whole primary afferents, we examined the combined effects of process location and afferent morphology on depolarization magnitude and latency, and the effect of activating synapses individually or simultaneously. Process location affects peak latency and voltage recorded at the heminode. A synapse on a calyceal process produced < or = 8% more depolarization and a 23% increase in peak latency compared with a synapse on a process of a neuron branch. For whole primary afferents, depolarization decreased 40% between simulations of the smallest and largest afferents. Simulations in which membrane resistivity and synaptic conductance were varied while afferent geometry was kept constant indicated that use of 5,000 omega cm2 and 1.0 nS produced results that best fit electrophysiological findings. Synaptic inputs activated simultaneously did not sum linearly at the heminode. Total depolarization was approximately 14% less than a simple summation of responses of synapses activated one at a time.(ABSTRACT TRUNCATED AT 400 WORDS)
Distribution and functional properties of 5-HT3 receptors in the rat hippocampal dentate gyrus: a patch-clamp study
Authors: Kawa K.
Published: December 2017

1. In dentate gyrus of rat hippocampal slices two distinct types of neurons, principal excitatory neurons (granule cells) and local inhibitory neurons (basket cells), could be identified under Nomarski microscopy; I investigated the actions of serotonin using the whole-cell patch-clamp technique. The identification of the neurons was later confirmed by intracellular staining with Lucifer yellow. 2. In both basket cells and granule cells, whole-cell current recordings revealed spontaneous synaptic currents ranging from < 10 pA to > 200 pA in symmetrical Cl- conditions at a holding potential of -63 mV. These currents were blocked by 10 microM bicuculline, indicating that they resulted from the spontaneous activation of GABAergic inputs (which had been morphologically described in both types of neurons). 3. By focal application of serotonin (2–50 microM) to basket cells under current clamp I evoked a train of action potentials superimposed on a baseline membrane depolarization. Under voltage-clamp conditions serotonin evoked an inward current at a holding potential of -63 mV (currents were detectable in approximately 90% of basket cells studied). The inward current was accompanied by a multitude of small inward currents of short duration (< 100 ms) that were found to be due to the stimulation by serotonin of nearby GABAergic presynaptic neurons innervating the recorded neuron. 4. In granule cells (total of 11 cells) serotonin did not produce any responses under conditions similar to those used for basket cells. The occurrence of bicuculline-sensitive spontaneous synaptic current events seemed to increase during the application of serotonin; this phenomenon reflected the excitatory action of serotonin exclusively on GABAergic interneurons. 5. The serotonin-induced inward currents in basket cells were mediated by the 5-HT3 receptor subtype because 1) they were blocked by either metoclopramide (10 microM) or [3-alpha-tropanyl]-1H-indolecarboxylic acid ester (2 nM), the latter being a specific blocker for the 5-HT3 receptor subtype, and 2) almost similar currents were induced by the application of the selective 5-HT3 receptor agonist 2-methyl 5-HT (2–50 microM) or 1-(m-chlorophenyl)-biguanide (0.1–10 microM). 6. Current-voltage (I–V) relations of serotonin-induced currents in basket cells showed that the reversal potential was close to 0 mV in external standard saline and depended on the concentrations of monovalent cations. I–V relations of serotonin-induced currents revealed inward rectification at the membrane potential range of +30 to -60 mV.(ABSTRACT TRUNCATED AT 400 WORDS)
Processing of frequency-modulated sounds in the cat's anterior auditory field
Authors: Tian B. , Rauschecker J. P.
Published: December 2017

1. Single-neuron activity was recorded from the anterior auditory field (AAF) in the cortex of gas-anesthetized cats. 2. Tone bursts and broad-band complex sounds were used for auditory stimulation. Responses to frequency-modulated (FM) sounds, in particular, were studied systematically. 3. Linear FM sweeps were centered around the best frequency (BF) of a neuron and had an excursion large enough to cover its whole frequency tuning range. Rate and direction of change of the FM sweeps were varied. 4. In 69% of the FM responses, a peak was found at an instantaneous frequency that corresponded to the BF in the pure-tone response. Thirty-three percent of the units had multiple maxima in their FM response. These secondary maxima were not always reflected in the pure-tone response of the same neurons. 5. The vast majority of AAF neurons showed one of two types of selectivity for FM rate. Depending on the criterion, almost half of the cells (46%) preferred fast changes of > 200 Hz/ms (high-pass) in both FM directions. Forty-eight percent of all neurons showed band-pass behavior with a clear preference in the middle range of FM rates in one or both directions. Low-pass or all-pass neurons made up only a small proportion (4 and 1%, respectively) of AAF neurons. 6. When both directions of an FM sweep (low-to-high and high-to-low-frequency) were tested, 66% of the neurons clearly were selective for one direction. This selectivity was not present necessarily at the preferred FM rate. In general, FM direction selectivity was most pronounced at slower FM rates. 7. The selectivity of AAF neurons for the rate and direction of FM sounds makes these neurons suitable for the detection and analysis of communication sounds, which often contain FM components with a particular sweep rate and direction.
Trans-ACPD, a metabotropic receptor agonist, produces calcium mobilization and an inward current in cultured cerebellar Purkinje neurons
Authors: Linden D. J. , Smeyne M. , Connor J. A.
Published: December 2017

1. 1-aminocyclopentane-trans-1,3-dicarboxylic acid (t-ACPD), a racemic mixture of 1-aminocyclopentane-1S,3R-dicarboxylic acid and 1-aminocyclopentane-1R,3S-dicarboxylic acid, a selective agonist of the metabotropic glutamate receptor, was applied to mouse Purkinje neurons (PNs) in culture. Measurements of free intracellular Ca2+ were made using fura-2 microfluorimetric imaging and of membrane current using perforated-patch voltage-clamp recording in separate experiments. 2. Brief pulses of t-ACPD (< or = 100 microM, 1–5 s) consistently produced a large (200–600 nM) increase in dendritic Ca2+ that was sometimes followed by a somatic increase. The dendrites typically returned to basal Ca2+ levels within 10–30 s. 3. Ca2+ increases produced by t-ACPD were measured in Ca(2+)-free external saline [0.5 mM ethylene glycol-bis(beta-amino-ethyl ether)-N,N,N',N'-tetraacetic acid (EGTA)], suggesting that they result from intracellular mobilization rather than influx. In addition, Ca2+ increases were not attenuated by a mixture of DL-AP5 and 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) [antagonists of N-methyl-D-aspartate (NMDA) and AMPA/kainate receptors, respectively], but were almost entirely eliminated by L-AP3 (100 microM), a putative metabotropic receptor antagonist or by preincubation of the cultures in pertussis toxin. 4. Brief pulses of t-ACPD (10 microM) produced a small inward current that was associated with an increase in membrane conductance. This current was reversibly blocked by L-AP3 but not by treatments that attenuate some voltage-gated K+ currents. Thus this current is unlikely to underlie the depolarization that is produced by metabotropic agonists in hippocampal pyramidal cells by K(+)-channel closure. 5. The t-ACPD induced inward current was attenuated by substitution of external Na+ with Li+ or choline, or by application of the membrane-permeable Ca2+ chelator, bis-(2-aminophenoxy)-N,N,N',N'- tetraacetic acid (BAPTA)/AM. One mechanism that could mediate this current is electrogenic Nao/Cai exchange, triggered by Ca2+ mobilization.
The activity of interneurons during locomotion in the in vitro necturus spinal cord
Authors: Wheatley M. , Jovanovic K. , Stein R. B. , Lawson V.
Published: December 2017

1. Less than two segments of the cervical spinal cord of the mudpuppy (Necturus maculatus) is sufficient to generate a locomotor rhythm with application of N-methyl-D-aspartic acid (NMDA). We have recorded intracellularly from rhythmically active interneurons in these segments and classified them according to their phase of firing within the step cycle and their afferent input. 2. Four classes of interneurons were found: flexor, flexor-->extensor, extensor, and extensor-->flexor. Interneurons that burst during the transition from flexion to extension or vice versa are referred to as “transitional” interneurons and represent the majority (68%) of rhythmically active interneurons studied in the mudpuppy spinal cord. 3. All flexor interneurons received only inhibitory input from cutaneous and dorsal root afferents, whereas the flexor-->extensor interneurons that responded received only excitatory input from dorsal root and cutaneous afferents. All extensor interneurons and all but one extensor-->flexor interneuron received no afferent input from the cutaneous or dorsal root afferents we stimulated. 4. Other interneurons have been classified as “tonic” cells. They fire continuously when the mudpuppy is walking and are silent when the mudpuppy is not walking. These interneurons receive no afferent input from the sources tested and may be responsible for turning locomotion on and off. 5. In conclusion, the presence of many transitional interneurons with specific patterns of afferent input may be required for the phasing of legged locomotion. We believe the in vitro preparation of the mudpuppy spinal cord and forelimb is an excellent model for studying the firing properties of interneurons during legged locomotion.
Characterization of mechanosensitive pelvic nerve afferent fibers innervating the colon of the rat
Authors: Sengupta J. N. , Gebhart G. F.
Published: December 2017

1. Single-unit activity was recorded from S1 sacral dorsal root afferent fibers in the anesthetized rat. A total of 364 afferent fibers were identified by electrical stimulation of the pelvic nerve and subsequently tested for response to colorectal distension (CRD) and urinary bladder distension (UBD). Sixty-seven percent (n = 244) of the fibers were unmyelinated C-fibers and 33% (n = 120) were thinly myelinated A delta-fibers. 2. In three initial experiments, 35 fibers were identified by pelvic nerve stimulation and tested for response only to CRD; none of these fibers responded to CRD. In 20 subsequent experiments, 329 pelvic nerve afferent fibers were tested for response to CRD and UBD. Thirty-four percent (n = 112) of the 329 fibers were unresponsive to noxious CRD (80 mmHg) or to UBD (slow filling < or = 100 mmHg), 44% (n = 146) responded to UBD, 16% (n = 53) responded to CRD, and 6% (n = 18) responded to mechanical stimulation of the anal mucosa. 3. Of the total of 53 pelvic nerve afferent fibers that responded to CRD, 43 (81%) were C-fibers (mean: 1.5 m/s) and 10 (19%) were A delta-fibers (mean: 4.7 m/s). Fifteen of the CRD-sensitive fibers had no resting activity, whereas 38 fibers exhibited some resting activity (mean: 2.6 imp/s). 4. Reproducibility of responses to repeated CRD (80 mmHg, 30s, 10 trials at 4-min intervals) was tested in 17 fibers. In 16, responses to repeated distension were reproducible without evidence of facilitation or inhibition of subsequent responses. One fiber gave greater responses during the 9th and 10th trials. 5. Responses to graded CRD were studied in 44 fibers. All fibers exhibited monotonic, increasing stimulus-response functions < or = 80 mmHg of distension. Thresholds for response of the 44 fibers were determined after extrapolation of the least-squares linear-regression line to the ordinate and varied between 0 and 40 mmHg. Two populations of pelvic nerve afferent fibers in the colon were apparent: low threshold (LT) afferent fibers had a mean threshold of 2.9 mmHg (range: 0-10 mmHg; n = 34) and high threshold (HT) afferent fibers had a mean threshold of 32.6 mmHg (range: 28.0–40.0 mmHg; n = 10). 6. Chemosensitivity to bradykinin (BK) was tested in nine LT fibers. Seven fibers responded to BK (0.1 to 100 micrograms/kg ia) and two fibers did not respond up to 100 micrograms/kg of BK. Responses to BK tested in three fibers were dose dependent.(ABSTRACT TRUNCATED AT 400 WORDS)
Characterization of the membrane ion currents of a model molluscan muscle, the accessory radula closer muscle of Aplysia californica. III. Depolarization-activated Ca current
Authors: Brezina V. , Evans C. G. , Weiss K. R.
Published: December 2017

1. The accessory radula closer (ARC) muscle of Aplysia californica and its innervation is a model preparation for the study of the neural and cellular mechanisms of behavioral plasticity. Much of the plasticity is due to modulation of contractions of the muscle by a variety of neurotransmitters and peptide cotransmitters. Preliminary to investigating the cellular mechanisms of this modulation, we have characterized the major membrane ion currents present in the unmodulated ARC muscle and their likely roles in normal contraction. We have studied single dissociated but functionally intact ARC muscle fibers under voltage clamp. This is the last of three papers describing this work. In the first paper we characterized two currents prominent at hyperpolarized voltages, a classical inwardly rectifying K current and a Cl current induced by elevated intracellular Cl-. In the second paper we examined two large outward K currents activated at more depolarized voltages, an “A” current and a delayed rectifier. 2. In this paper, we describe an inward depolarization-activated Ca current that underlies and is normally completely masked by the K currents and is revealed when they are blocked. 3. The Ca current begins to activate above -40 or -30 mV. It is fully available for activation at voltages more negative than -60 mV. It activates in milliseconds, then inactivates relatively slowly with maintained depolarization. The current is larger and inactivates slower when it is carried by Ba2+ rather than Ca2+. The inactivation is current rather than voltage dependent. The current is blocked by Co2+, Cd2+, and with a characteristic time dependence, by the dihydropyridine Ca-channel antagonist nifedipine. 4. These properties of the current characterize it as a high-threshold, L-type Ca current. 5. This current most likely provides Ca2+ necessary for contraction of the ARC muscle.