bluuebunny/crossref_metadata_2025 huggingface dataset:
Involvement of NMDA receptors in the respiratory phase transition is different in the adult guinea pig in vivo and in the isolated brain stem preparation
Authors: Morin-Surun M. P. , Boudinot E. , Kato F. , Foutz A. S. , Denavit-Saubie M.
Published: December 2017

1. We investigated the involvement of N-methyl-D-aspartate (NMDA) receptors in the respiratory pattern in an in vitro preparation of adult brain stem compared with in vivo conditions in the guinea pig. 2. In vivo, combining administration of the NMDA channel blocker dizocilpine (MK-801) (3 mg/kg) with a surgical section of the vagus nerves induced an apneustic type of respiration characterized by long inspiratory “holds,” as has been shown in other species. The same effect was observed in hypothermic animals (30 degrees C). 3. The isolated in vitro brain stems from these apneustic animals did not present a prolonged inspiratory phase. A second dose of dizocilpine (100 microM perfused vascularly did not induce apneusis, even after increasing brain stem temperature to 35.5 degrees C. 4. In another group of isolated brain stems of adult guinea pigs anesthetized with pentobarbital sodium before decapitation, we perfused dizocilpine and NMDA through the basilar artery. The duration of periodic inspiratory motor activity recorded from the hypoglossal nerve was unaffected by dizocilpine (1–100 microM) or the competitive NMDA antagonist D- or DL-2-amino-5-phosphonopentanoic acid (100 microM and 1 mM), although respiratory frequency decreased. The increase in respiratory activity produced by vascularly perfused NMDA (25–100 microM) was blocked by dizocilpine (100 microM). 5. We conclude that the central mechanism of inspiratory termination in the vagotomized adult guinea pig requires the activation of NMDA receptors in vivo but not in vitro. This difference is not due to the hypothermic environment in vitro. Possible mechanisms for phase switching in vitro are discussed.
Effective synaptic current and motoneuron firing rate modulation
Authors: Powers R. K. , Binder M. D.
Published: December 2017

1. We used a modified voltage-clamp technique to measure the steady-state effective synaptic currents (I(N)) produced by activating four different input systems to cat hindlimb motoneurons: Ia afferent fibers, Ia-inhibitory interneurons, Renshaw interneurons, and contralateral rubrospinal neurons. In the same motoneurons, we measured the slope of the firing rate-injected current (f-I) relation in the primary range. We then reactivated these synaptic inputs during steady, repetitive firing to assess their effects on motoneuron discharge rate. 2. Our measurements of I(N) were derived from recordings made near the resting membrane potential, whereas the effects of the synaptic inputs on repetitive discharge were evaluated at more depolarized membrane potentials. Thus we adjusted the I(N) values for these changes in driving force based on estimates of the synaptic reversal potential and the mean membrane potential during repetitive discharge. 3. We found that changes in the steady-state discharge rate of a motoneuron produced by these synaptic inputs could be reasonably well predicted by the product of the estimated value of I(N) during repetitive firing and the slope of the motoneuron's f-I relation. Although there was a high correlation between predicted and observed changes in firing rate for our entire sample of motoneurons (r = 0.93; P < 0.001), the slope of the relation between predicted and observed firing rate modulation was significantly greater than 1. 4. The systematic difference between predicted and observed firing rate modulation observed in the overall sample was primarily due to the fact that our predictions underestimated the changes in firing rate produced by Ia excitation and Ia inhibition.(ABSTRACT TRUNCATED AT 250 WORDS)
Low-voltage activated calcium currents increase in basal forebrain neurons from aged rats
Authors: Murchison D. , Griffith W. H.
Published: December 2017

1. Whole cell patch-clamp recordings were made of low-voltage-activated (LVA) calcium (Ca2+) currents using 2 mM barium (Ba2+) as charge carrier. Acutely dissociated neurons from medial septum (MS) and the nucleus of the diagonal band (nDB) were examined in young adult (1–3 mo) and aged (24–26 mo) Fischer 344 rats. 2. Most neurons in both age groups displayed LVA currents: 84% of young cells (110/131) and 87% in aged cells (62/71). Using cell capacitance as an indication of cell size, aged cells were significantly smaller (P < 0.05; 15.4 +/- 0.6 pF; mean +/- SE) than young cells (18.0 +/- 0.5 pF), although a single distribution of cell sizes was present in both populations. 3. The LVA currents were enhanced in cells from aged animals. When LVA currents were studied without activation of high voltage activated currents, the current density (pA/pF) was significantly (P < 0.05) increased at negative potentials in aged neurons (young: 4.92 +/- 0.35 pA/pF; Aged: 5.92 +/- 0.45 pA/pF, at a prepulse potential of -110 mV). No change in voltage-dependent activation or inactivation was seen. The time course of recovery from inactivation also was unchanged. 4. Kinetic parameters of LVA currents were compared in both age groups. No age-related difference in time-dependent activation or inactivation was observed. A single distribution of decay time constants of LVA currents was present in both age groups. 5. These results show that MS/nDB cells maintain robust LVA currents and have increased current densities in very old rats. An increased LVA current in the aged neurons suggests that their ability to fire rhythmically or in bursts is retained or enhanced and that the resulting increase in intracellular Ca2+ may contribute to an altered Ca2+ homeostasis.
Modulation of muscle responses evoked by transcranial magnetic stimulation during the acquisition of new fine motor skills
Authors: Pascual-Leone A. , Nguyet D. , Cohen L. G. , Brasil-Neto J. P. , Cammarota A. , Hallett M.
Published: December 2017

1. We used transcranial magnetic stimulation (TMS) to study the role of plastic changes of the human motor system in the acquisition of new fine motor skills. We mapped the cortical motor areas targeting the contralateral long finger flexor and extensor muscles in subjects learning a one-handed, five-finger exercise on the piano. In a second experiment, we studied the different effects of mental and physical practice of the same five-finger exercise on the modulation of the cortical motor areas targeting muscles involved in the task. 2. Over the course of 5 days, as subjects learned the one-handed, five-finger exercise through daily 2-h manual practice sessions, the cortical motor areas targeting the long finger flexor and extensor muscles enlarged, and their activation threshold decreased. Such changes were limited to the cortical representation of the hand used in the exercise. No changes of cortical motor outputs occurred in control subjects who underwent daily TMS mapping but did not practice on the piano at all (control group 1). 3. We studied the effect of increased hand use without specific skill learning in subjects who played the piano at will for 2 h each day using only the right hand but who were not taught the five-finger exercise (control group 2) and who did not practice any specific task. In these control subjects, the changes in cortical motor outputs were similar but significantly less prominent than in those occurring in the test subjects, who learned the new skill.(ABSTRACT TRUNCATED AT 250 WORDS)
Reexamination of the effects of MCPG on hippocampal LTP, LTD, and depotentiation
Authors: Selig D. K. , Lee H. K. , Bear M. F. , Malenka R. C.
Published: December 2017

1. We examined the effects of the metabotropic glutamate receptor (mGluR) antagonist alpha-methyl-4-carboxyphenylglycine (MCPG) on the induction of long-term potentiation (LTP) long-term depression (LTD), and depotentiation in CA1 hippocampal neurons using extracellular recording techniques. 2. MCPG (500 microM) strongly antagonized the presynaptic inhibitory action of the mGluR agonist 1-aminocyclopentane-(1S,3R)-dicarboxylic acid yet failed to block LTP induced with either tetanic stimulation (100 Hz, 1 s) or theta-burst stimulation. 3. To test the possibility that our failure to block LTP was due to prior activation of a "molecular switch" that in its "on" state obviates the need for mGluR activation to generate LTP, we gave repeated periods of prolonged low-frequency stimulation (LFS; 1 Hz, 10 min), a manipulation reported to turn the switch "off." Although this stimulation saturated LTD, subsequent application of MCPG still failed to block LTP. 4. MCPG did not block LFS-induced depotentiation in older slices (4-6 wk) or LFS-induced LTD in older, young (11-18 days), or neonatal (3-7 days) slices. 5. These results demonstrate that MCPG-sensitive mGluRs are not necessary for the induction of LTP, LTD, or depotentiation in hippocampal CA1 pyramidal cells. The possibility remains, however, that their activation may modify the threshold for the induction of these long-term plastic changes.
Slowly inactivating outward currents in a cuticular mechanoreceptor neuron of the cockroach (Periplaneta americana)
Authors: Torkkeli P. H. , French A. S.
Published: December 2017

1. Although rapid adaptation is a widespread feature of sensory receptors, its ionic basis has not been clearly established in any touch receptor, because their small sizes have severely restricted the range of experiments tat can be performed. In the cockroach tactile spine, intracellular voltage-clamp recordings are now possible. 2. The basic electrophysiological properties of the cockroach femoral tactile spine neuron were studied using discontinuous (switching) single-electrode current- and voltage-clamp recordings. A slowly inactivating voltage-sensitive K+ outward current was detected after the major inward currents were blocked with tetrodotoxin. 3. The total outward current activated in < 1 ms at voltages above 0 mV. At moderate depolarizations it did not inactivate, but at higher depolarizations an inactivation time constant of approximately 260 ms was measured. Some recordings also revealed an additional, slower inactivation time constant of approximately 2.5 s. 4. More than half of the voltage-sensitive K+ outward current could be blocked with the Ca2+ channel blockers Co2+ and Cd2+. Tetraethylammonium chloride (TEA) also reduced the amplitude of the outward current to about half of its original amplitude. The actions of both blockers were reversible and probably reflect overlapping blockades of two separate outward currents. 5. The reversal potentials of the currents that remained after block with Co2+ (-91.7 mV) or TEA (-86.8 mV) were both near the K+ equilibrium potential expected for the tactile spine neuron. The voltage dependencies of activation of the Co(2+)- and TEA-resistant currents were both well fitted by Boltzmann distributions, giving values of half maximal activation (V50) equal to -34.5 mV for the Co(2+)-resistant current and -51.3 mV for the TEA-resistant current. 6. Current-clamp recordings revealed that the TEA-sensitive K+ current was the major component of action potential repolarization but that it did not effect the frequency of action potentials evoked by steady depolarization. On the other hand, blockers of Ca(2+)-sensitive K+ currents (Cd2+, Co2+, or charybdotoxin) reduced adaptation and increased the frequency of action potentials significantly but did not effect the duration or amplitude of individual action potentials.
Dynamics of neurons in the cat lateral geniculate nucleus: in vivo electrophysiology and computational modeling
Authors: Mukherjee P. , Kaplan E.
Published: December 2017

1. We investigated the time domain transformation that thalamocortical relay cells of the cat lateral geniculate nucleus (LGN) perform on their retinal input, and used computational modeling to explore the biophysical properties that determine the dynamics of the LGN relay cells in vivo. 2. We recorded simultaneously the input (S potentials) and output (action potentials) of 50 cat LGN relay cells stimulated by drifting sinusoidal gratings of varying temporal frequency. The temporal modulation transfer functions (TMTFs) of the neurons were derived from these data. The burstiness of the LGN spike trains was also assessed using objective criteria. 3. We found that the form of the TMTF was quite variable among cells, ranging from low-pass to strongly band-pass. The optimal temporal frequency of band-pass neurons was between 2 and 8 Hz. In addition, the TMTF of some cells was nonstationary: their temporal tuning changed with time. 4. The temporal tuning of a cell was directly related to the degree of burstiness of its spike train. Tonically firing relay cells had low-pass TMTFs, whereas the most bursty neurons exhibited the most sharply band-pass transfer functions. This was also true for single cells that altered their temporal tuning: a shift to more band-pass tuning was associated with increased burstiness of the spike train, and vice versa. 5. We constructed a computer simulation of the LGN relay cell. The model was a simplified five-channel version of the thalamocortical neuron model of McCormick and Huguenard. It incorporated the quantitative kinetics of the Ca2+ T channel, as well as the Hodgkin-Huxley Na+ and K+ channels, as the only active membrane currents. To simulate the in vivo dynamics of the relay cell, the input to the model consisted of trains of synaptic potentials, recorded as S potentials in our physiological experiments. 6. When the resting membrane potential of the model neuron was relatively depolarized, the model's TMTF was low-pass, with no bursting evident in the simulated spike train. At hyperpolarized resting membrane potentials, however, the modeled TMTF was band-pass, with frequent burst discharges. Thus the biophysical model reproduced not only the range of dynamics seen in real LGN relay cells, but also the dependence of the overall dynamics on the burstiness of the spike train. However, neither of these phenomena could be simulated without the T channel. Thus the simulations demonstrated that the T-type Ca2+ channel was necessary and sufficient to explain the LGN dynamics observed in physiological experiments.(ABSTRACT TRUNCATED AT 400 WORDS)
Evidence for common expression mechanisms underlying heterosynaptic and associative long-term depression in the dentate gyrus
Authors: Christie B. R. , Stellwagen D. , Abraham W. C.
Published: December 2017

1. The extent to which heterosynaptic and prime-associative stimulation protocols generate different forms of long-term depression (LTD) was assessed in the lateral perforant path synapses terminating on dentate gyrus granule cells in pentobarbital-anesthetized rats. 2. Heterosynaptic LTD was induced in the lateral path by repeated tetanization of the medial path. Prime-associative LTD of the lateral path was induced by alternating high-frequency conditioning trains to the medial path and single shocks to the lateral path at 100-ms intervals, all occurring 10 min after priming stimulation of the lateral path (5 Hz, 80 pulses). 3. Induction of LTD by one administration of the prime-associative protocol was normally greater in magnitude than the LTD induced by the heterosynaptic protocol. Saturation of LTD by repeated delivery of the prime-associative protocol completely occluded the subsequent induction of LTD by the heterosynaptic protocol. Saturation of LTD by repeated delivery of the heterosynaptic protocol produced an 80% occlusion of the LTD generated by the prime-associative protocol. 4. These data support the hypothesis that activity-dependent (associative) and activity-independent (heterosynaptic) LTD involve overlapping expression mechanisms, despite having demonstrably different induction mechanisms.
Comparison of the responses to moving texture patterns of simple and complex cells in the cat's area 17
Authors: Casanova C. , Savard T. , Nordmann J. P. , Molotchnikoff S. , Minville K.
Published: December 2017

1. Whether complex (C) cells are the only truly texture-sensitive units in the cat's primary visual cortex remains controversial. In view of the strong physiological significance of having putatively only one class of cells sensitive to visual noise in the striate cortex, we reinvestigated this issue. Sensitivities of simple (S) and C cells to noise were quantitatively studied and compared in order to clearly document the response properties of cells in the striate cortex to visual noise and to establish whether one can unequivocally segregate S from C cells on the basis of those specific properties. 2. Receptive fields were stimulated with all relevant stimuli, i.e., drifting sine-wave gratings, electronically generated noise pattern of 256 x 256 elements (ratio 1:1 of dark and light elements), and flashing and moving bars (both bright and dark). 3. A total of 60 S cells out of 85 (70.6%) and 90 C cells out of 101 (81.8%) responded to the motion of visual noise. Responses of most C cells were sustained, i.e., their discharge rate was maintained at a constant level throughout presentation of the stimulus. On the other hand, responses of the majority of S cells were characterized by several bursts of discharges. On average, optimal firing rates were greater for gratings than for noise. 4. For practically all cells, responses to noise varied as a function of direction of motion. The mean direction bandwidths were, respectively, 43 +/- 24 degrees and 48 +/- 23 degrees (mean +/- SD) for S and C cells. In both groups, neurons were more broadly tuned for the direction of noise than that of gratings (t-test, P < 0.001). We rarely observed bimodal tuning curves for noise, with each peak lying on either side of the orientation curve. These results could be expected if one considers texture stimuli not in the space domain (as dot patterns) but in the frequency domain, i.e., patterns containing all spatial frequencies and orientations. 5. In general, the direction indexes of S and C cells were similar whether they were stimulated by drifting noise or gratings. S cells had a slight tendency to be more direction selective for noise than for gratings. 6. For all S and C cells tested, responses to noise varied as a function of drift velocity. The mean optimal velocity was 12.9 and 10.2 degrees/s for S and C cells, respectively (t-test, P > 0.05). Most cells were band-pass with mean bandwidths of 2.2 and 2.7 octaves for S and C cells, respectively.(ABSTRACT TRUNCATED AT 400 WORDS)
Predictive human pursuit and "orbital goal" of microstimulated smooth eye movements
Authors: van Gelder P. , Lebedev S. , Tsui W. H.
Published: December 2017

1. Anticipatory saccades in smooth pursuit move the point of gaze from near the moving target to well ahead of it, interrupting accurate smooth pursuit. Their effects on the pursuit process were studied in 22 normal human subjects. We presented horizontal periodic target trajectories of 30 degrees amplitude and 30 degrees/s constant velocity or 0.4 Hz sinusoidal velocity in 40-s trials. Saccades and surrounding smooth eye movement (SEM) segments were marked and classified by computer. 2. Anticipatory saccades were often followed by slowed SEM that tended to intercept the target at the endpoint of its trajectory. This was seen in the distribution of projections of the initial 60 ms of postsaccadic SEM to the time of the trajectory endpoint. Magnitude of this SEM tended to follow a function of the time and location of the endpoint of the anticipatory saccade, decreasing as the anticipatory saccades landed closer to the trajectory endpoint. 3. The time and location of the target trajectory endpoint seemed to be the goal for this SEM. We believe this to demonstrate the predictive use of the period and amplitude of the trajectory in smooth pursuit, apart from the instantaneous velocity match of the target. 4. Gottlieb and coworkers in the frontal eye field and Ron and Robinson in the cerebellum produced SEMs in the monkey by microstimulation. At some sites in both structures, direction and velocity of the SEMs depended on the initial position of the eye in that the elicited SEMs appeared to be converging toward a common point, or "orbital goal", and the SEM velocity diminished as the gaze neared that goal.2+ Both our SEM after anticipatory saccades and microstimulated SEM in the monkey slowed as the initial position was brought closer to the inferred orbital goal. This similarity suggests that the goal-directed SEM sites in the monkey might be part of a mechanism for predictive pursuit.
Spontaneous activity and frequency selectivity of acoustically responsive vestibular afferents in the cat
Authors: McCue M. P. , Guinan J. J.
Published: December 2017

1. Recordings were made from single afferent fibers in the inferior vestibular nerve. Firing rates of a substantial portion of the afferents with irregular background activity increased in response to moderately intense tone bursts. 2. Spontaneous activity from acoustically responsive vestibular afferents was statistically analyzed and compared with data from a more widespread sampling of primary afferents in the cat's vestibulocochlear nerve. Acoustically responsive vestibular afferents had interspike interval histograms with modes > 10 ms, coefficients of variation > 0.15, and skews > 0.88. On the basis of spontaneous activity, these afferents were easily distinguishable from cochlear afferents and regular vestibular afferents, but no obvious features differentiated them from other irregular vestibular afferents. 3. The distributions of spike intervals in the spontaneous activity of acoustically responsive vestibular afferents were fitted by Erlang probability density functions describing the second-order interarrival times of a Poisson process initiated after a finite delay (refractory period). 4. Acoustically responsive vestibular afferents had broad, V-shaped tuning curves with best frequencies between 500 and 1,000 Hz, thresholds of > or = 90 dB SPL, and shapes comparable with the tuning-curve “tails” of cochlear afferents. In contrast to cochlear-nerve afferents, acoustically responsive vestibular afferents did not show a strong relationship between spontaneous rate and threshold. 5. We compare the acoustic frequency selectivity of vestibular and cochlear afferents in terms of their functional and evolutionary relationships. Our data and those of others indicate that acoustically responsive vestibular afferents are likely to provide an input to the acoustic activation of the sternocleidomastoid muscle in humans, and they may provide an input to other acoustic reflexes such as the middle-ear-muscle reflexes.
Responses of neurons in the auditory pathway of the barn owl to partially correlated binaural signals
Authors: Albeck Y. , Konishi M.
Published: December 2017

1. Extracellular single-unit recording in anesthetized barn owls was used to study neuronal response to dichotic stimuli of variable binaural correlation (BC). Recordings were made in the output fibers of nucleus laminaris (NL), the anterior division of the ventral lateral lemniscal nucleus (VLVa), the core of the central nucleus of the inferior colliculus (ICcC), the lateral shell of the central nucleus of the inferior colliculus (ICcLS), and the external nucleus of the inferior colliculus (ICx). 2. The response of all neurons sensitive to interaural time difference (ITD) varied with BC. The relationship between BC and impulse number fits a linear, a parabolic, or a ramp model. A linear or parabolic model fits most neurons in low-level nuclei. Higher order neurons in ICx did not respond to noise bursts with strong negative binaural correlation, creating a ramp-like response to BC. 3. A neuron's ability to detect ITD varied as a function of BC. Conversely, a neuron's response to BC changed with ITD. Neurons in NL, VLVa, and ICcC show almost periodic ITD response curves. In these neurons peaks and troughs of ITD response curves diminished as BC decreased, creating a flat ITD response when BC = 0. When BC was set to -1, the most favorable ITD became the least favorable one and vice versa. The ITD response curve of ICx neurons usually has a single dominant peak. The response of those neurons to a negatively correlated noise pair (BC = -1) showed two ITD peaks, flanking the position of the primary peak. 4. The parabolic BC response of NL neurons fits the prediction of the cross-correlation model, assuming half-wave rectification of the sound by the cochlea. Linear response is not predicted by the model. However, the parabolic and the linear neurons probably do not belong to two distinct groups as the difference between them is not statistically significant. Thus, the cross-correlation model provides a good description of the binaural response not only in NL but also in VLVa and ICcC. 5. Almost all ramp neurons occurred in either ICx or ICcLS where neurons are more broadly tuned to frequency than those in the lower nuclei. The synthesis of this response type requires, however, not only the convergence of different frequency channels but also inhibition between different ITD channels. We modeled the ramp response as a three-step process. First, different spectral channels converge to create broad frequency tuning. The response to variation in BC will be linear (or parabolic) because it is a sum of linear (parabolic) responses. Second, the activity in some adjacent ITD channels is subtracted by lateral inhibition. Finally, the result is rectified using a high threshold to avoid negative activity.
Neurons in the globus pallidus do not show correlated activity in the normal monkey, but phase-locked oscillations appear in the MPTP model of parkinsonism
Authors: Nini A. , Feingold A. , Slovin H. , Bergman H.
Published: December 2017

1. To test the mode of functional connectivity in the basal ganglia circuitry, we studied the activity of simultaneously recorded neurons in the globus pallidus (GP) of a behaving rhesus monkey. The cross-correlograms of pairs of neurons in the GP were compared with those of neurons in the thalamus and frontal cortex and to the cross-correlograms of pallidal pairs after 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) treatment. 2. In contrast with cortical and thalamic neuronal activity, almost all pairs (n = 76/81 pairs; 93.8%, 1,629/1,651 histograms; 98.7%) of GP neurons in the normal monkey were not driven by a common input. 3. The monkey was systemically treated with MPTP until the appearance of parkinsonian signs and an intermittent 7- to 11-Hz action/postural tremor. After the MPTP treatment, many pallidal neurons (49/140; 35%) became oscillatory, and 19% (n = 31/162) of pallidal pairs had oscillatory cross-correlograms. 4. These results support the model of parallel processing in the basal ganglia of normal monkeys and suggest a breakdown of the independent activity in the parkinsonian state.
Inwardly rectifying potassium conductance can accelerate the hyperpolarizing response in retinal horizontal cells
Authors: Dong C. J. , Werblin F. S.
Published: December 2017

1. We studied the activation properties and assessed the functional role of the inwardly rectifying potassium conductance (GK.IR) in acutely isolated retinal horizontal cells (HCs) with the use of the whole cell patch-clamp technique. 2. The potassium current mediated by GK.IR was isolated by the use of Cs+ or Ba2+ ions. This current was outward, although relatively small in amplitude, in the voltage range between the potassium equilibrium potential (EK) and 50-60 mV more positive. The current reversed its polarity at EK and became inward at potentials more negative than EK. When HCs were bathed in normal Ringer (EK = -90 mV), GK.IR began to active at about -30 mV, was 30-40% activated at the resting potential (-70 to -80 mV) and about fully activated at -130 mV. Thus a significant portion of the activation range of GK.IR overlaps the HC physiological response range (-20 to -80 mV). 3. GK.IR has a dramatic effect on the kinetics of membrane polarization. Blocking GK.IR with Cs+ or Ba2+ significantly slowed the rate of membrane hyperpolarization in response to a hyperpolarizing current ramp over the HC physiological response range. Blocking GK.IR also dramatically slowed the onset rate of a simulated light response generated by a brief break in a sustained glutamate puff. 4. These results suggest that GK.IR can enhance the temporal resolution of the HC by accelerating the onset rate of the hyperpolarizing light response.
Intrinsic neuromodulation in the Tritonia swim CPG: serotonin mediates both neuromodulation and neurotransmission by the dorsal swim interneurons
Authors: Katz P. S. , Frost W. N.
Published: December 2017

1. Neuromodulation has previously been shown to be intrinsic to the central pattern generator (CPG) circuit that generates the escape swim of the nudibranch mollusk Tritonia diomedea; the dorsal swim interneurons (DSIs) make conventional monosynaptic connections and evoke neuromodulatory effects within the swim motor circuit. The conventional synaptic potentials evoked by a DSI onto cerebral neuron 2 (C2) and onto the dorsal flexion neurons (DFNs) consist of a fast excitatory postsynaptic potential (EPSP) followed by a prolonged slow EPSP. In their neuromodulatory role, the DSIs produce an enhancement of the monosynaptic connections made by C2 onto other CPG circuit interneurons and onto efferent flexion neurons. Previous work showed that the DSIs are immunoreactive for serotonin. Here we provide evidence that both the neurotransmission and the neuromodulation evoked by the DSIs are produced by serotonin, and that these effects may be pharmacologically separable. 2. Previously it was shown that bath-applied serotonin both mimics and occludes the modulation of the C2 synapses by the DSIs. Here we find that pressure-applied puffs of serotonin mimic both the fast and slow EPSPs evoked by a DSI onto a DFN, whereas high concentrations of bath-applied serotonin occlude both of these synaptic components. 3. Consistent with the hypothesis that serotonin mediates the actions of the DSIs, the serotonin reuptake inhibitor imipramine prolongs the duration of the fast DSI-DFN EPSP, increases the amplitude of the slow DSI-DFN EPSP, and increases both the amplitude and duration of the modulation of the C2-DFN synapse by the DSIs. 4.Two serotonergic antagonists were found that block the actions of the DSIs. Gramine blocks the fast DSI-DFN EPSP, and has far less of an effect on the slow EPSP and the modulation. Gramine also diminishes the depolarization evoked by pressure-applied serotonin, showing that it is a serotonin antagonist in this system. In contrast, methysergide greatly reduces both the slow EPSP and the modulation evoked by the DSIs, but has mixed effects on the fast EPSP. Methysergide also blocks the ability of exogenous serotonin to enhance the C2-DFN EPSP, demonstrating that it antagonizes the serotonin receptors responsible for this modulation. 5. Taken together with previous work, these results indicate that serotonin is likely to be responsible for all three actions of the DSIs that were examined: the fast and slow DSI-DFN EPSPs and the neuromodulation of the C2-DFN synapse. These results also indicate that the conventional and neuromodulatory effects of the DSIs may be pharmacologically separable. In future work it may be possible to determine the functional role of each in the swim circuit.
Light responses from one type of ON-OFF amacrine cells in the rabbit retina
Authors: Dacheux R. F. , Raviola E.
Published: December 2017

1. The light responses from one type of ON-OFF amacrine cell were recorded intracellularly in the superfused rabbit retina under various conditions of light adaptation. These recordings were obtained from cells located in a central area. 5-7 mm inferior and directly below the optic nerve head. 2. ON-OFF amacrine cells responded to the initiation and termination of light stimuli with transient depolarizations. Their receptive fields were approximately 0.8-1 mm diam and did not exhibit antagonistic center-and-surround organization. 3. The cells received rod input because they responded to very dim scotopic stimuli. With prolonged dark adaptation, the cells became more sensitive to the initiation than termination of the stimulus, because the ON component of the light response had a lower threshold than the OFF component. 4. The cells continued to respond to test flashes when the retina was adapted to a background illumination of rod-saturating intensity. Thus ON-OFF amacrine cells also receive cone input. Under these photopic conditions, a secondary afterpotential was observed following the OFF component. Its characteristics were different from those of the rod aftereffect reported in other retinal cells of the rabbit because its latency and amplitude changed with increasing stimulus intensity. 5. Intracellular injections of horseradish peroxidase showed that the recordings were obtained from a class of ON-OFF amacrine cells whose wide-field, unistratified dendrites were rigorously confined to the middle of the inner plexiform layer or stratum 3. 6. The conspicuous rod and cone inputs into a class of amacrine cells that are connected neither to rod bipolars nor to All amacrine cells strongly support the idea that in the rabbit the rod pathway uses cone bipolars as interneurons to distribute scotopic signals to ganglion and cone-driven amacrine cells.
Mechanical perturbation of cultured cortical neurons reveals a stretch-induced delayed depolarization
Authors: Tavalin S. J. , Ellis E. F. , Satin L. S.
Published: December 2017

1. An in vitro cellular model of injury was used to elucidate mechanisms contributing to traumatic brain injury (TBI). Neonatal rat cortical neurons cultured on a flexible silastic membrane were stretched rapidly and reversibly by a 50-ms pulse of pressurized air. 2. Sublethal cell stretch depolarized neuronal resting membrane potential by approximately 10 mV but only if cells were incubated for 1 h after injury. Stretch-induced delayed depolarization (or SIDD) returned to baseline values within 24 h. 3. SIDD was dependent on the degree of cell stretch and required neuronal firing, calcium entry, and N-methyl-D-aspartate receptor activation for its induction but not its maintainance. 4. Similarities between SIDD and TBI suggest that SIDD may play a role in brain injury.
Self-reinnervated cat medial gastrocnemius muscles. I. comparisons of the capacity for regenerating nerves to form enlarged motor units after extensive peripheral nerve injuries
Authors: Rafuse V. F. , Gordon T.
Published: December 2017

1. The aims of this study are to determine 1) whether regenerating motor axons have the capacity to form enlarged motor units (MUs) in muscles reinnervated by few motoneurons and 2) whether the type of nerve injury, repair, and/or growth environment affects this capacity. 2. MU innervation ratio (IR) was estimated by measuring isometric unit tetanic force in reinnervated cat medial gastrocnemius muscles 3-16 mo after denervation by either 1) crushing its nerve, 2) transecting the nerve and suturing the proximal end to the distal stump (N-N suture), or 3) transecting the nerve and suturing the proximal end directly to the muscle fascia (N-M suture). In addition, the number of regenerating axons was experimentally reduced by cutting one of two contributing ventral roots. 3. Muscles were reinnervated by 2-88% of their normal complement of MUs. Mean unit tetanic force increased as the number of reinnervated MUs decreased in reinnervated muscles after nerve crush or N-N suture, but not after N-M suture, even when few axons made functional connections. When the number of MUs was < 20% of normal, mean unit force was significantly higher in reinnervated muscles after nerve crush compared with muscle reinnervated after N-N suture. 4. The cross-sectional areas (CSAs) of all muscle fiber types were similar to normal in reinnervated muscles after nerve crush, but the CSAs of type IIa and IIb fibers were significantly smaller in muscles reinnervated after complete nerve transections (i.e., N-N or N-M sutures). 5. When MU force was normalized to mean muscle fiber CSA, cut motor axons displayed the same capacity to form enlarged MUs as crushed motor axons. The force of the MUs increased by as much as 5-8 times that of normal, provided the axons grew along the distal nerve stump (N-N suture). 6. Tetanic force increased in the normal order slow < fast-fatigue resistant < fast-fatigue intermediate = fast-fatigable. However, the increase in tetanic force of the slow (S) units was significantly larger than the corresponding increase of the more forceful fast (F) units. The disproportional increase in S and not F unit force, was primarily due to a significant decline in CSA of the type IIa and IIb muscle fibers. 7. The technique of glycogen depletion was used to count MU fibers to estimate the IR of MUs in 5 normal and 11 reinnervated muscles (7 N-N sutures, 4 N-M sutures). Unit tetanic force covaried with IR in both normal and reinnervated muscles. 8. These results show that regenerating axons have the same capacity as intact axons in partially denervated muscles to form enlarged MUs to compensate for a reduced number of functioning MUs. Only when axons regenerate in the absence of the distal nerve sheath is this capacity compromised.
Monte Carlo simulation of fast excitatory synaptic transmission at a hippocampal synapse
Authors: Wahl L. M. , Pouzat C. , Stratford K. J.
Published: December 2017

1. A simulation of fast excitatory synaptic transmission at a hippocampal synapse is presented. Individual neurotransmitter molecules are followed as they diffuse through the synaptic cleft and interact with the postsynaptic receptors. The ability of the model to reproduce published results of patch-clamp experiments on CA3 pyramidal cells is illustrated; parameters of the model that affect the time course and variability of the excitatory postsynaptic current (EPSC) are then investigated. 2. To simulate an EPSC, we release 4,000 neurotransmitter molecules simultaneously from a point source centered 15 nm above a rectangular grid of 14 x 14 postsynaptic receptors. The simulated EPSC at room temperature has a 10-90% rise time of 0.28 ms and a peak open probability of 0.27, and decays with a time constant of 2.33 ms, comparing well with values in the literature. 3. To simulate changes in temperature, we use a 10 degrees temperature coefficient (Q10) for diffusion of 1.3 and apply a Q10 of 3.0 to all the rate constants of the kinetic scheme. At 37 degrees C, the 10-90 rise time is 0.07 ms, the peak open probability is 0.56, and the decay time constant is 0.70 ms. The coefficient of variation (CV) at the peak of the EPSC is 9.4% at room temperature; at 37 degrees C, the CV at the peak drops to 6.6%. 4. We use the diffusion coefficient of glutamine, 7.6 x 10(-6) cm2/s, to model the random movement of glutamate molecules in the synaptic cleft. Slower rates of diffusion increase the peak response and slow the time course of decay of the EPSC. 5. Random variations in release site position have little effect on the time course of the average EPSC or on the CV of the peak response. We simulate a dose-response curve for the effects of releasing between 100 and 7,500 neurotransmitter molecules per vesicle. The half-maximal response occurs for 1,740 molecules. For a simulation with 100 postsynaptic receptors and a diffusion coefficient of 2.0 x 10(-6) cm2/s, 4,000 molecules approaches a saturating dose. 6. Changes to the width of the synaptic cleft, or to the number and spacing of the postsynaptic receptors, have marked effects on the peak height of the simulated EPSC. 7. We extend the model to include a spherical vesicle (50 nm diam) connected to the synaptic cleft by a cylindrical pore 15 nm long. Neurotransmitter molecules are randomly distributed within the vesicle and allowed to diffuse into the synaptic cleft through the pore, which opens to its full diameter in one time step. We find that the pore must open to a diameter of > or = 7 nm within 1 microsecond in order to match the time courses of EPSCs in the literature.
Serotonin modulates N- and P-type calcium currents in neocortical pyramidal neurons via a membrane-delimited pathway
Authors: Foehring R. C.
Published: December 2017

1. The effects of serotonin (5HT) on neocortical pyramidal neurons were studied using whole cell and ON-cell patch-clamp recordings from acutely dissociated neurons. 2. 5HT decreased high voltage-activated calcium channel currents in a dose-dependent and reversible manner in acutely dissociated neocortical pyramidal neurons. The maximum block was 30% of the peak whole cell current (at -10 mV). 3. The 5HT modulation was mimicked by 5HT1A agonists and was reduced by 5HT1A antagonists. 5HT2 antagonists had no effect on the modulation. These data suggest that the 5HT effects were mediated by 5HT1A receptors. 4. The 5HT1A modulation was reduced in the presence of the specific N-type blocker omega-conotoxin GVIA (CgTx) and by the P-type channel blocker omega-agatoxin IVA (AgTx), but not by the L-type blocker nifedipine. 5HT did not modulate the slowed tail currents in the presence of the dihydropyridine agonist Bay K 8644. These data suggest that N- and P-type channels (but not L-type channels) were targeted by 5HT. 5. The modulation involved G proteins and utilized a membrane-delimited pathway. The modulation was rapid in onset (tau approximately 600 ms) and offset. About 50% of the reduction in current by 5HT1A agonists was overcome by prepulses to 120 mV. 6. Slowing of current onset kinetics in response to 5HT1A agonists was seen rarely in neocortical pyramidal neurons (11% of cases). The presence of slowing depended on agonist concentration, being evident only with high micromolar doses.
Histamine depolarizes cholinergic septal neurons
Authors: Gorelova N. , Reiner P. B.
Published: December 2017

1. Bath application of 10 microM histamine (HA) resulted in a depolarization or inward current in 58/59 cholinergic neurons located in the medial septum and nucleus of the diagonal band of Broca (MS/DBB) in a slice preparation of rat brain. 2. In bridge mode, the histamine-induced depolarization consisted of both fast and slow phases; inward currents that followed the comparable time course were observed under voltage-clamp conditions. The fast depolarization was associated with variable changes in input resistance, while the slow depolarization always was associated with an increase in input resistance. 3. Both fast and slow responses persisted in the presence of tetrodotoxin (TTX), but only the fast response persisted when transmitter release was abolished by bathing the slice in either a low-Ca(2+)-, high-Mg(2+)-containing medium or one containing Cd2+. 4. When ramp voltage-clamp commands were applied during the fast depolarization, the resultant current-voltage (I-V) curves did not intersect over the range of membrane potentials from -130 to -30 mV. Ionic substitution experiments suggested that the bulk of the ionic current flowing during the fast depolarization was carried by sodium ions. 5. The I-V characteristics of the slow inward current identified it as a reduction in an inwardly rectifying potassium conductance. 6. The fast depolarization was significantly reduced by the H1 receptor antagonists pyrilamine and promethazine, but not by the H2 receptor antagonist cimetidine. Neither the H2 receptor agonist impromidine nor the H3 receptor agonist R-alpha-methylhistamine mimicked the response to HA. None of the agonists or antagonists had any observable effect upon the slow depolarization. 7. We conclude that HA directly depolarizes cholinergic MS/DBB neurons by acting as an H1 receptor, which primarily couples to an increase in a TTX-insensitive Na+ conductance. Additionally, HA evokes a slow depolarization mediated by a decrease in an inwardly rectifying potassium conductance but is not generated by activation of classically defined HA receptor subtypes.
Spatially tuned auditory responses in area LIP of macaques performing delayed memory saccades to acoustic targets
Authors: Mazzoni P. , Bracewell R. M. , Barash S. , Andersen R. A.
Published: December 2017

1. The lateral intraparietal area (area LIP) of the macaque's posterior parietal cortex (PPC) lies in the dorsal stream of extrastriate visual areas. It receives extensive visual inputs and sends outputs to several eye movement centers. It contains neurons with visual and saccade-related responses suggesting a role of area LIP in programming saccadic eye movements to visual targets. Because primates can also orient to nonvisual stimuli, we investigated whether LIP neurons process stimuli of other modalities besides the visual one by comparing their activity in auditory and visual saccade tasks. 2. We recorded the activity of single neurons of Macaca mulatta monkeys while they performed memory saccades to acoustic and visual targets. We analyzed the activity during stimulus presentation (stimulus period, S) and during the delay (memory period, M) between stimulus presentation and the saccade to its remembered location. 3. Among 80 area LIP neurons tested, we found 44 that had S period and/or M period responses following presentation of the auditory stimulus. Most of these responses were spatially tuned, i.e., selective for the left or right stimulus location (27 of 29 S responses; 25 of 29 M responses). 4. The majority of neurons with responses in the auditory memory saccade task also responded in the visual version of the task. Eighty-nine percent (24/27) were clearly bimodal in the S period, and 88% (23/26) were bimodal in the M period. 5. Almost all the neurons with spatially tuned auditory responses that were bimodal were also spatially tuned in their visual responses (20/22 for S responses; 18/19 for M responses). The spatial tuning for the two modalities was the same in 85% (17/20) of the tested neurons for the S responses, and in 83% (15/18) of the tested neurons for the M responses. 6. Area LIP contains a population of neurons that respond to both visual and auditory stimuli. This result is consistent with our finding that the memory activity of many LIP cells encodes the next planned saccade. If cells are coding planned movements, they should be active independently of the sensory modality of the target for the movement, as was the case for most of the neurons described in the present study.