Fast Amplification of Dynamic Synaptic Inputs in Spinal Motoneurons In Vivo

2006 ◽  
Vol 96 (5) ◽  
pp. 2200-2206 ◽  
Author(s):  
Sarah M. Jones ◽  
Robert H. Lee

The ability of voltage-dependent inward currents (likely Na+) of the adult cat lumbar motoneurons to amplify rapidly changing (i.e., dynamic) synaptic inputs was investigated using in vivo intracellular recording techniques. Fast amplification was assessed by measuring the magnitude of the high-frequency (180 Hz) component of the Ia synaptic input due to tendon vibration as a function of somatic voltage and was compared with the previously observed amplification of steady inputs (steady state response of PICs to slow inputs). Data from 17 experiments show that amplification of the dynamic input indeed occurred and was directly linked to neuromodulatory drive (standard state: decerebrate with intact descending neuromodulatory systems vs. minimal state: pentobarbital with said systems significantly inhibited). Fast amplification factors averaged 2.0 ± 0.7 (mean ± SD) in the standard neuromodulatory state. That is, the effective synaptic current was nearly twice as large at its peak as it was at hyperpolarized levels, ranging as high as 2.6. Although fast amplification was often smaller than the amplification of steady inputs, the difference was not statistically significant. However, the voltage at which fast amplification began was ∼10 mV more depolarized ( P < 0.01). It is concluded that both dynamic and steady inputs can be amplified, but there may be differences in mechanism.

1999 ◽  
Vol 81 (4) ◽  
pp. 1531-1547 ◽  
Author(s):  
Alain Destexhe ◽  
Denis Paré

Impact of network activity on the integrative properties of neocortical pyramidal neurons in vivo. During wakefulness, neocortical neurons are subjected to an intense synaptic bombardment. To assess the consequences of this background activity for the integrative properties of pyramidal neurons, we constrained biophysical models with in vivo intracellular data obtained in anesthetized cats during periods of intense network activity similar to that observed in the waking state. In pyramidal cells of the parietal cortex (area 5–7), synaptic activity was responsible for an approximately fivefold decrease in input resistance ( R in), a more depolarized membrane potential ( V m), and a marked increase in the amplitude of V m fluctuations, as determined by comparing the same cells before and after microperfusion of tetrodotoxin (TTX). The model was constrained by measurements of R in, by the average value and standard deviation of the V m measured from epochs of intense synaptic activity recorded with KAc or KCl-filled pipettes as well as the values measured in the same cells after TTX. To reproduce all experimental results, the simulated synaptic activity had to be of relatively high frequency (1–5 Hz) at excitatory and inhibitory synapses. In addition, synaptic inputs had to be significantly correlated (correlation coefficient ∼0.1) to reproduce the amplitude of V m fluctuations recorded experimentally. The presence of voltage-dependent K+ currents, estimated from current-voltage relations after TTX, affected these parameters by <10%. The model predicts that the conductance due to synaptic activity is 7–30 times larger than the somatic leak conductance to be consistent with the approximately fivefold change in R in. The impact of this massive increase in conductance on dendritic attenuation was investigated for passive neurons and neurons with voltage-dependent Na+/K+ currents in soma and dendrites. In passive neurons, correlated synaptic bombardment had a major influence on dendritic attenuation. The electrotonic attenuation of simulated synaptic inputs was enhanced greatly in the presence of synaptic bombardment, with distal synapses having minimal effects at the soma. Similarly, in the presence of dendritic voltage-dependent currents, the convergence of hundreds of synaptic inputs was required to evoke action potentials reliably. In this case, however, dendritic voltage-dependent currents minimized the variability due to input location, with distal apical synapses being as effective as synapses on basal dendrites. In conclusion, this combination of intracellular and computational data suggests that, during low-amplitude fast electroencephalographic activity, neocortical neurons are bombarded continuously by correlated synaptic inputs at high frequency, which significantly affect their integrative properties. A series of predictions are suggested to test this model.


2005 ◽  
Vol 94 (6) ◽  
pp. 3961-3974 ◽  
Author(s):  
Sherif M. ElBasiouny ◽  
David J. Bennett ◽  
Vivian K. Mushahwar

We used computer simulations to study the dendritic spatial distribution of low voltage-activated L-type calcium (CaV1.3 type) channels, which mediate hysteretic persistent inward current (PIC) in spinal motoneurons. This study was prompted by the growing experimental evidence of the functional interactions between synaptic inputs and active conductances over the motoneuron dendritic tree. A compartmental cable model of an adult cat α-motoneuron was developed in NEURON simulation environment constituting the detailed morphology of type-identified triceps surae α-motoneuron and realistic distribution of group Ia afferent-to-motoneuron contacts. Simulations of different distributions of CaV1.3 channels were conducted and the resultant behavior was compared to experimental data. Our results suggest that CaV1.3 channels do not uniformly cover the whole motoneuron dendritic tree. Instead, their distribution is similar to that of synaptic contacts. We found that CaV1.3 channels are primarily localized to a wide intermediate band overlapping with the dendritic Ia-synaptic territory at dendritic distances of 300 to 850 μm (0.62 ± 0.21λ) from the soma in triceps surae α-motoneurons. These findings explain the functional interaction between synaptic inputs and the CaV1.3 channels over the motoneuron dendritic tree.


2017 ◽  
Vol 118 (1) ◽  
pp. 93-102 ◽  
Author(s):  
Seoan Huh ◽  
Ramamurthy Siripuram ◽  
Robert H. Lee ◽  
Vladimir V. Turkin ◽  
Derek O’Neill ◽  
...  

The majority of studies on the electrical properties of neurons are carried out in rodents, and in particular in mice. However, the minute size of this animal compared with humans potentially limits the relevance of the resulting insights. To be able to extrapolate results obtained in a small animal such as a rodent, one needs to have proper knowledge of the rules governing how electrical properties of neurons scale with the size of the animal. Generally speaking, electrical resistances of neurons increase as cell size decreases, and thus maintenance of equal depolarization across cells of different sizes requires the underlying currents to decrease in proportion to the size decrease. Thus it would generally be expected that voltage-sensitive currents are smaller in smaller animals. In this study, we used in vivo preparations to record electrical properties of spinal motoneurons in deeply anesthetized adult mice and cats. We found that PICs do not scale with size, but instead are constant in their amplitudes across these species. This constancy, coupled with the threefold differences in electrical resistances, means that PICs contribute a threefold larger depolarization in the mouse than in the cat. As a consequence, motoneuronal firing rate sharply increases as animal size decreases. These differences in firing rates are likely essential in allowing different species to control muscles with widely different contraction speeds (smaller animals have faster muscle fibers). Thus from our results we have identified a possible new mechanism for how electrical properties are tuned to match mechanical properties within the motor output system. NEW & NOTEWORTHY The small size of the mouse warrants concern over whether the properties of their neurons are a scaled version of those in larger animals or instead have unique features. Comparison of spinal motoneurons in mice to cats showed unique features. Firing rates in the mouse were much higher, in large part due to relatively larger persistent inward currents. These differences likely reflect adaptations for controlling much faster muscle fibers in mouse than cat.


2000 ◽  
Vol 83 (2) ◽  
pp. 1108-1114 ◽  
Author(s):  
L. López-Aguado ◽  
J. M. Ibarz ◽  
O. Herreras

During synchronous action potential (AP) firing of CA1 pyramidal cells, a population spike (PS) is recorded in the extracellular space, the amplitude of which is considered a reliable quantitative index of the population output. Because the AP can be actively conducted and differentially modulated along the soma and dendrites, the extracellular part of the dendritic inward currents variably contributes to the somatic PS by spreading in the volume conductor to adjacent strata. This contribution has been studied by current-source density analysis and intracellular recordings in vivo during repetitive backpropagation that induces their selective fading. Both the PS and the ensemble action currents declined during high-frequency activation, although at different rates and timings. The decline was much stronger in dendrites than in the somatic region. At specific frequencies and for a short number of impulses the decrease of the somatic PS was neither due to fewer firing cells nor to decreased somatic action currents but to the blockade of dendritic action currents. The dendritic contribution to the peak of the somatic antidromic PS was estimated at ∼30–40% and up to 100% at later times in the positive-going limb. The blockade of AP dendritic invasion was in part due to a decreased transfer of current from the soma that underwent a cumulative increase of conductance and slow depolarization during the train that eventually extended into the axon. The possibility of differential modulation of soma and dendritic action currents during APs should be checked when using the PS as a quantitative parameter.


1991 ◽  
Vol 155 (1) ◽  
pp. 435-453
Author(s):  
KARIN SCHIRRMACHER ◽  
JOACHIM W. DEITMER

Voltage-dependent Na+ and Ca2+ inward currents underlying the action potential in cultured embryonic ganglion cells of the leech Hirudo medicinalis have been investigated using the gigaseal whole-cell current or voltage-clamp technique. Dissociated ganglion cells were isolated from 7- to 14-day-old embryos, and maintained in primary culture for up to 5 days. More than 95% of the cultured cells had voltage-dependent K+ currents and about 75% of the cells had voltagedependent inward currents. Action potentials of 60mV amplitude and 4 ms duration, similar to those in embryonic nerve cells in vivo, could be recorded. Three types of inward currents occurred in these cells: (1) an initial Na+ current, which activated and inactivated rapidly; (2) a second Na+ current, which activated slowly and persisted during membrane depolarization, showing very little inactivation, and (3) a Ca2+-dependent inward current. Both types of Na+ currents were resistant to tetrodotoxin (TTX, 0.2-5 μmol l−1). The Ca+ current was also carried by Ba2+, and was blocked by cobalt and cadmium. The fast Na+ current was first expressed in cells from 8-day-old embryos, 1 day earlier than the Ca2+ current. Between days 8 and 14 the density of the fast Na+ current increased from 22±3 to 51±6 μA cm−2 (±S.D., N=11), while the Ca2+ current grew from 10 μA cm−1 (N=2) to 15±4 μA cm−2 (N=10) during this time.


2012 ◽  
Vol 108 (3) ◽  
pp. 753-759 ◽  
Author(s):  
Randall K. Powers ◽  
Paul Nardelli ◽  
T. C. Cope

Voltage-dependent calcium and sodium channels mediating persistent inward currents (PICs) amplify the effects of synaptic inputs on the membrane potential and firing rate of motoneurons. CaPIC channels are thought to be relatively slow, whereas the NaPIC channels have fast kinetics. These different characteristics influence how synaptic inputs with different frequency content are amplified; the slow kinetics of Ca channels suggest that they can only contribute to amplification of low frequency inputs (<5 Hz). To characterize frequency-dependent amplification of excitatory postsynaptic potentials (EPSPs), we measured the averaged stretch-evoked EPSPs in cat medial gastrocnemius motoneurons in decerebrate cats at different subthreshold levels of membrane potential. EPSPs were produced by muscle spindle afferents activated by stretching the homonymous and synergist muscles at frequencies of 5–50 Hz. We adjusted the stretch amplitudes at different frequencies to produce approximately the same peak-to-peak EPSP amplitude and quantified the amount of amplification by expressing the EPSP integral at different levels of depolarization as a percentage of that measured with the membrane hyperpolarized. Amplification was observed at all stretch frequencies but generally decreased with increasing stretch frequency. However, in many cells the amount of amplification was greater at 10 Hz than at 5 Hz. Fast amplification was generally reduced or absent when the lidocaine derivative QX-314 was included in the electrode solution, supporting a strong contribution from Na channels. These results suggest that NaPICs can combine with CaPICs to enhance motoneuron responses to modulations of synaptic drive over a physiologically significant range of frequencies.


1998 ◽  
Vol 80 (2) ◽  
pp. 583-593 ◽  
Author(s):  
R. H. Lee ◽  
C. J. Heckman

Lee, R. H. and C. J. Heckman. Bistability in spinal motoneurons in vivo: systematic variations in persistent inward currents. J. Neurophysiol. 80: 583–593, 1998. Bistable behavior in spinal motoneurons consists of self-sustained firing evoked by a brief period of input. However, not all motoneurons possess an equal capacity for bistable behavior. In the companion paper, we found that self-sustained firing was persistent for long periods only in motoneurons with low rheobases and slow axonal conduction velocities. High rheobase, fast conduction velocity motoneurons tend to be only partially bistable in that self-sustained firing lasts at most 1–2 s. The mechanisms underlying these differences between fully and partially bistable motoneurons were investigated by measuring their current voltage ( I-V) relationships in the decerebrate cat preparation after administration of the noradrenergic α1 agonist methoxamine. Slow (8 mV/s) triangular voltage commands were applied using the discontinuous single-electrode voltage-clamp technique. Both fully and partially bistable cells exhibited a region of negative I-V slope due to activation of a strong, persistent inward current. The peak amplitude of the total persistent inward current ( I PIC) was equally large in fully and partially bistable cells, but there were substantial differences in how I PIC was activated and deactivated. In fully bistable cells, the offset of I PIC on the descending phase of the triangular voltage command occurred at a substantially more hyperpolarized voltage then its onset on the rising phase. Thus the I-V function of fully bistable cells exhibited marked hysteresis. Partially bistable cells had significantly less hysteresis. The lack of hysteresis in partially bistable cells was due to a greater decay of I PIC with time than that seen in fully bistable cells. Furthermore, the range over which activation and deactivation of I PIC occurred was more depolarized in partially than in fully bistable cells. The I-V functions were compared with frequency-current ( F-I) functions from the same cells, the characteristics of which were presented in the companion paper. The strong onset-offset difference in I PIC in fully bistable cells corresponded to a similarly large hysteresis for the thresholds of their F-I functions. The reduced onset-offset difference for I PIC in partially bistable cells corresponded to a lack of hysteresis in F-I thresholds. Thus the properties of I PIC accounted for the main differences in the F-I behavior seen between fully and partially bistable cells.


1979 ◽  
Vol 236 (4) ◽  
pp. H657-H663
Author(s):  
S. H. Nellis ◽  
A. J. Liedtke

A low mechanical impedance strain gauge that imposed insignificant preload to the myocardial fibers was tested in vitro and in vivo. The dynamic response of the gauge to an abrupt change in length (step response) and to sinusoidal perturbation was determined. The electrical output reached 95% of maximum steady-state response within 3-5 ms after a step displacement. Frequency analysis indicated a flat response up to 80 oscillations/s. The in vivo testings of the gauges were performed on intact, working swine hearts during control and ischemic flows in a regionally perfused preparation. During control perfusion the gauges demonstrated epicardial shortening in systole and early-to-mid diastole. Relaxation was confined to late diastole. With ischemic perfusion there was a progressive loss of systolic shortening, but minimal disruption in global hemodynamics. Correlative measurements were also made with sonomicrometers positioned in subepicardial myocardium. Patterns of motion, shortening, and changes in strain were similar between the two types of gauges.


1986 ◽  
Vol 51 (4) ◽  
pp. 362-369 ◽  
Author(s):  
Donna M. Risberg ◽  
Robyn M. Cox

A custom in-the-ear (ITE) hearing aid fitting was compared to two over-the-ear (OTE) hearing aid fittings for each of 9 subjects with mild to moderately severe hearing losses. Speech intelligibility via the three instruments was compared using the Speech Intelligibility Rating (SIR) test. The relationship between functional gain and coupler gain was compared for the ITE and the higher rated OTE instruments. The difference in input received at the microphone locations of the two types of hearing aids was measured for 10 different subjects and compared to the functional gain data. It was concluded that (a) for persons with mild to moderately severe hearing losses, appropriately adjusted custom ITE fittings typically yield speech intelligibility that is equal to the better OTE fitting identified in a comparative evaluation; and (b) gain prescriptions for ITE hearing aids should be adjusted to account for the high-frequency emphasis associated with in-the-concha microphone placement.


1973 ◽  
Vol 29 (02) ◽  
pp. 490-498 ◽  
Author(s):  
Hiroh Yamazaki ◽  
Itsuro Kobayashi ◽  
Tadahiro Sano ◽  
Takio Shimamoto

SummaryThe authors previously reported a transient decrease in adhesive platelet count and an enhancement of blood coagulability after administration of a small amount of adrenaline (0.1-1 µg per Kg, i. v.) in man and rabbit. In such circumstances, the sensitivity of platelets to aggregation induced by ADP was studied by an optical density method. Five minutes after i. v. injection of 1 µg per Kg of adrenaline in 10 rabbits, intensity of platelet aggregation increased to 115.1 ± 4.9% (mean ± S. E.) by 10∼5 molar, 121.8 ± 7.8% by 3 × 10-6 molar and 129.4 ± 12.8% of the value before the injection by 10”6 molar ADP. The difference was statistically significant (P<0.01-0.05). The above change was not observed in each group of rabbits injected with saline, 1 µg per Kg of 1-noradrenaline or 0.1 and 10 µg per Kg of adrenaline. Also, it was prevented by oral administration of 10 mg per Kg of phenoxybenzamine or propranolol or aspirin or pyridinolcarbamate 3 hours before the challenge. On the other hand, the enhancement of ADP-induced platelet aggregation was not observed in vitro, when 10-5 or 3 × 10-6 molar and 129.4 ± 12.8% of the value before 10∼6 molar ADP was added to citrated platelet rich plasma (CPRP) of rabbit after incubation at 37°C for 30 second with 0.01, 0.1, 1, 10 or 100 µg per ml of adrenaline or noradrenaline. These results suggest an important interaction between endothelial surface and platelets in connection with the enhancement of ADP-induced platelet aggregation by adrenaline in vivo.


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