scholarly journals Kv3.3 subunits control presynaptic action potential waveform and neurotransmitter release at a central excitatory synapse

2021 ◽  
Author(s):  
Amy Richardson ◽  
Victoria Ciampani ◽  
Mihai Stancu ◽  
Sherylanne Newton ◽  
Joern R. Steinert ◽  
...  
Keyword(s):  
Signal To Noise Ratio ◽  
Computational Modelling ◽  
Auditory Brainstem ◽  
Synaptic Activity ◽  
Delayed Rectifier ◽  
Short Term ◽  
High Frequencies ◽  
Action Potential Waveform ◽  
Activity Dependent ◽  
Potential Waveform

Kv3 potassium currents mediate rapid repolarization of action potentials (AP), supporting fast spikes and high repetition rates. Of the four Kv3 gene family members, Kv3.1 and Kv3.3 are highly expressed in the auditory brainstem and we exploited this to test for subunit-specific roles at the calyx of Held presynaptic terminal. Deletion of Kv3.3 (but not Kv3.1) increased presynaptic AP duration and facilitated transmitter release, which in turn enhanced short-term depression during high frequency transmission. The response to sound was delayed in the Kv3.3KO, with higher spontaneous and lower evoked firing, thereby reducing signal-to-noise ratio. Computational modelling showed that the enhanced EPSC and short-term depression in the Kv3.3KO reflected increased vesicle release probability and accelerated activity-dependent vesicle replenishment. We conclude that Kv3.3 is the presynaptic delayed rectifier, enabling short duration, precisely timed APs to maintain transmission at high frequencies and during sustained synaptic activity.

Comparisons of Auditory Brainstem Responses Between a Laboratory and Simulated Home Environment

2020 ◽  
Vol 63 (11) ◽  
pp. 3877-3892
Author(s):  
Ashley Parker ◽  
Candace Slack ◽  
Erika Skoe
Keyword(s):  
Home Environment ◽  
Signal To Noise Ratio ◽  
Auditory Brainstem ◽  
Auditory Brainstem Responses ◽  
Single Family ◽  
Adult Participants ◽  
Simulated Home Environment ◽  
Brainstem Response ◽  
Research Populations ◽  
Response Consistency

Purpose Miniaturization of digital technologies has created new opportunities for remote health care and neuroscientific fieldwork. The current study assesses comparisons between in-home auditory brainstem response (ABR) recordings and recordings obtained in a traditional lab setting. Method Click-evoked and speech-evoked ABRs were recorded in 12 normal-hearing, young adult participants over three test sessions in (a) a shielded sound booth within a research lab, (b) a simulated home environment, and (c) the research lab once more. The same single-family house was used for all home testing. Results Analyses of ABR latencies, a common clinical metric, showed high repeatability between the home and lab environments across both the click-evoked and speech-evoked ABRs. Like ABR latencies, response consistency and signal-to-noise ratio (SNR) were robust both in the lab and in the home and did not show significant differences between locations, although variability between the home and lab was higher than latencies, with two participants influencing this lower repeatability between locations. Response consistency and SNR also patterned together, with a trend for higher SNRs to pair with more consistent responses in both the home and lab environments. Conclusions Our findings demonstrate the feasibility of obtaining high-quality ABR recordings within a simulated home environment that closely approximate those recorded in a more traditional recording environment. This line of work may open doors to greater accessibility to underserved clinical and research populations.

scholarly journals Action Potential Waveform Variability Limits Multi-Unit Separation in Freely Behaving Rats

PLoS ONE ◽  
2012 ◽  
Vol 7 (6) ◽  
pp. e38482 ◽  
Author(s):  
Peter Stratton ◽  
Allen Cheung ◽  
Janet Wiles ◽  
Eugene Kiyatkin ◽  
Pankaj Sah ◽  
...  
Keyword(s):  
Action Potential ◽  
Action Potential Waveform ◽  
Freely Behaving ◽  
Potential Waveform

Effects of ischemia and myogenic activity on active and passive mechanical properties of rat cerebral arteries

2002 ◽  
Vol 283 (6) ◽  
pp. H2268-H2275 ◽  
Author(s):  
Rebecca J. Coulson ◽  
Naomi C. Chesler ◽  
Lisa Vitullo ◽  
Marilyn J. Cipolla
Keyword(s):  
Contractile Activity ◽  
Cerebral Arteries ◽  
Biomechanical Properties ◽  
Short Term ◽  
Mechanical Stiffness ◽  
Middle Cerebral Arteries ◽  
Male Wistar Rats ◽  
Myogenic Activity ◽  
Activity Dependent

Passive (papaverine induced) and active (spontaneous pressure induced) biomechanical properties of ischemic and nonischemic rat middle cerebral arteries (MCAs) were studied under pressurized conditions in vitro. Ischemic (1 h of occlusion), contralateral, and sham-operated control MCAs were isolated from male Wistar rats ( n = 22) and pressurized using an arteriograph system that allowed control of transmural pressure (TMP) and measurement of lumen diameter and wall thickness. Three mechanical stiffness parameters were computed: overall passive stiffness (β), pressure-dependent modulus changes ( E inc,p), and smooth muscle cell (SMC) activity-dependent changes ( E inc,a). The β-value for ischemic vessels was increased compared with sham vessels (13.9 ± 1.7 vs. 9.1 ± 1.4, P < 0.05), indicating possible short-term remodeling due to ischemia. E inc,p increased with pressure in the passive vessels ( P < 0.05) but remained relatively constant in the active vessels for all vessel types, indicating that pressure-induced SMC contractile activity (i.e., myogenic reactivity) in cerebral arteries leads to the maintenance of a constant elastic modulus within the autoregulatory pressure range. E inc,a increased with pressure for all conditions, signifying that changes in stiffness are influenced by SMC activity and vascular tone.

Modeling short-term interval-force relations in cardiac muscle

2000 ◽  
Vol 278 (3) ◽  
pp. H913-H931 ◽  
Author(s):  
J. Jeremy Rice ◽  
M. Saleet Jafri ◽  
Raimond L. Winslow
Keyword(s):  
Ryanodine Receptor ◽  
Cell Model ◽  
Isometric Force ◽  
Delayed Rectifier ◽  
Short Term ◽  
Time Model ◽  
Receptor Adaptation ◽  
Myofilament Activation ◽  
Recirculation Fraction ◽  
Ventricular Cell Model

This study employs two modeling approaches to investigate short-term interval-force relations. The first approach is to develop a low-order, discrete-time model of excitation-contraction coupling to determine which parameter combinations produce the degree of postextrasystolic potentiation seen experimentally. Potentiation is found to increase 1) for low recirculation fraction, 2) for high releasable fraction, i.e., the maximum fraction of Ca2+released from the sarcoplasmic reticulum (SR) given full restitution, and 3) for strong negative feedback of the SR release on sarcolemmal Ca2+ influx. The second modeling approach is to develop a more detailed single ventricular cell model that simulates action potentials, Ca2+-handling mechanisms, and isometric force generation by the myofilaments. A slow transition from the adapted state of the ryanodine receptor produces a gradual recovery of the SR release and restitution behavior. For potentiation, a small extrasystolic release leaves more Ca2+ in the SR but also increases the SR loading by two mechanisms: 1) less Ca2+-induced inactivation of L-type channels and 2) reduction of action potential height by residual activation of the time-dependent delayed rectifier K+ current, which increases Ca2+ influx. The cooperativity of the myofilaments amplifies the relatively small changes in the Ca2+ transient amplitude to produce larger changes in isometric force. These findings suggest that short-term interval-force relations result mainly from the interplay of the ryanodine receptor adaptation and the SR Ca2+ loading, with additional contributions from membrane currents and myofilament activation.

Entrainment pattern between sympathetic and phrenic nerve activities in the Sprague-Dawley rat: hypoxia-evoked sympathetic activity during expiration

2004 ◽  
Vol 286 (6) ◽  
pp. R1121-R1128 ◽  
Author(s):  
Thomas E. Dick ◽  
Y.-H. Hsieh ◽  
Shaun Morrison ◽  
Sharon K. Coles ◽  
Nanduri Prabhakar
Keyword(s):  
Phrenic Nerve ◽  
Sympathetic Activity ◽  
Respiratory Pattern ◽  
Sprague Dawley ◽  
Short Term ◽  
Nerve Activity ◽  
Term Potentiation ◽  
Motor Activities ◽  
Respiratory Modulation ◽  
Activity Dependent

Sympathetic and respiratory motor activities are entrained centrally. We hypothesize that this coupling may partially underlie changes in sympathetic activity evoked by hypoxia due to activity-dependent changes in the respiratory pattern. Specifically, we tested the hypothesis that sympathetic nerve activity (SNA) expresses a short-term potentiation in activity after hypoxia similar to that expressed in phrenic nerve activity (PNA). Adult male, Sprague-Dawley (Zivic Miller) rats ( n = 19) were anesthetized (Equithesin), vagotomized, paralyzed, ventilated, and pneumothoracotomized. We recorded PNA and splanchnic SNA (sSNA) and generated cycle-triggered averages (CTAs) of rectified and integrated sSNA before, during, and after exposures to hypoxia (8% O2 and 92% N2 for 45 s). Inspiration (I) and expiration (E) were divided in half, and the average and area of integrated sSNA were calculated and compared at the following time points: before hypoxia, at the peak breathing frequency during hypoxia, immediately before the end of hypoxia, immediately after hypoxia, and 60 s after hypoxia. In our animal model, sSNA bursts consistently followed the I-E phase transition. With hypoxia, sSNA increased in both halves of E, but preferentially in the second rather than the first half of E, and decreased in I. After hypoxia, sSNA decreased abruptly, but the coefficient of variation in respiratory modulation of sSNA was significantly less than that at baseline. The hypoxic-evoked changes in sympathetic activity and respiratory pattern resulted in sSNA in the first half of E being correlated negatively to that in the second half of E ( r = −0.65, P < 0.05) and positively to Te ( r = 0.40, P < 0.05). Short-term potentiation in sSNA appeared not as an increase in the magnitude of activity but as an increased consistency of its respiratory modulation. By 60 s after hypoxia, the variability in the entrainment pattern had returned to baseline. The preferential recruitment of late expiratory sSNA during hypoxia results from either activation by expiratory-modulated neurons or by non-modulated neurons whose excitatory drive is not gated during late E.

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