scholarly journals Synaptic Transmission at the Calyx of Held Under In Vivo–Like Activity Levels

2007 ◽  
Vol 98 (2) ◽  
pp. 807-820 ◽  
Author(s):  
Joachim Hermann ◽  
Michael Pecka ◽  
Henrique von Gersdorff ◽  
Benedikt Grothe ◽  
Achim Klug

One of the hallmarks of auditory neurons in vivo is spontaneous activity that occurs even in the absence of any sensory stimuli. Sound-evoked bursts of discharges are thus embedded within this background of random firing. The calyx of Held synapse in the medial nucleus of the trapezoid body (MNTB) has been characterized in vitro as a fast relay that reliably fires at high stimulus frequencies (≤800 Hz). However, inherently due to the preparation method, spontaneous activity is absent in studies using brain stem slices. Here we first determine in vivo spontaneous firing rates of MNTB principal cells from Mongolian gerbils and then reintroduce this random firing to in vitro gerbil brain stem synapses at near-physiological temperature. After conditioning synapses with afferent fiber stimulation for 2 min at Poisson averaged rates of 20, 40, and 60 Hz, we observed a number of differences in the properties of synaptic transmission between conditioned and unconditioned synapses. Foremost, we observed reduced steady-state EPSC amplitudes that depressed even further during an embedded short-stimulation train of 100, 300, or 600 Hz (a protocol that thus simulates in vitro what probably occurs at the in vivo MNTB after a short sound stimulus in a silent background). Accordingly, current-clamp, dynamic-clamp, and loose-patch recordings revealed a number of action potential failures at the postsynaptic cell during high-frequency–stimulation trains, although the initial onset of evoked activity was still transmitted with higher fidelity. We thus propose that some in vivo auditory synapses are in a tonic state of reduced EPSC amplitudes as a consequence of high spontaneous spiking and this in vivo–like conditioning has important consequences for the encoding of signals throughout the auditory pathway.

2019 ◽  
Author(s):  
Paloma P Maldonado ◽  
Alvaro Nuno-Perez ◽  
Jan Kirchner ◽  
Elizabeth Hammock ◽  
Julijana Gjorgjieva ◽  
...  

SummarySpontaneous network activity shapes emerging neuronal circuits during early brain development, however how neuromodulation influences this activity is not fully understood. Here, we report that the neuromodulator oxytocin powerfully shapes spontaneous activity patterns. In vivo, oxytocin strongly decreased the frequency and pairwise correlations of spontaneous activity events in visual cortex (V1), but not in somatosensory cortex (S1). This differential effect was a consequence of oxytocin only increasing inhibition in V1 and increasing both inhibition and excitation in S1. The increase in inhibition was mediated by the depolarization and increase in excitability of somatostatin+ (SST) interneurons specifically. Accordingly, silencing SST+ neurons pharmacogenetically fully blocked oxytocin’s effect on inhibition in vitro as well its effect on spontaneous activity patterns in vivo. Thus, oxytocin decreases the excitatory/inhibitory ratio and modulates specific features of V1 spontaneous activity patterns that are crucial for refining developing synaptic connections and sensory processing later in life.


1980 ◽  
Vol 238 (2) ◽  
pp. E157-E166 ◽  
Author(s):  
M. J. Harper ◽  
L. W. Coons ◽  
D. A. Radicke ◽  
B. J. Hodgson ◽  
G. Valenzuela

Contractile activity of the ampulla of rabbit oviducts removed 24 h after an ovulating injection was studied in vitro. Spontaneous activity, field-stimulated activity, and response to phenylephrine were studied in normal, reversed, and scraped (endosalpinx removed) sections of tissues in the presence or absence of inhibitors of prostaglandin synthetase (8 or 51 micrograms/ml indomethacin or 10 or 100 micrograms/ml 5,8,11,14-eicosatetraynoic acid (ETA)). The effects of in vivo treatment with 10 mg/kg of indomethacin on the same responses were examined. Scraped tissues produced more prostaglandin E and F (measured by radioimmunoassay) than did normal tissues, and this production was suppressed by 10 micrograms/ml of indomethacin or 100 micrograms/ml of ETA. Production of prostaglandin by normal tissues was not depressed by these compounds in vitro, but was significantly reduced by pretreatment of the animals with indomethacin in vivo. In the absence of the endosalpinx, the myosalpinx exhibited spontaneous activity and responded to field stimulation and phenylephrine. Scraped and reversed tissues, however, showed a faster decline in response to field stimulation than normal tissues, and this was due to the traumatization. By contrast, traumatization increased the sensitivity of the tissue to respond to phenylephrine. Inhibition of prostaglandin synthetase by low doses of indomethacin or ETA prevented desensitization of the tissue to field stimulation, but this desensitization was little affected by the higher doses of indomethacin in vitro or in vivo. ETA did not affect the phenylephrine dose-response curves and nor did 8 micrograms/ml of indomethacin, whereas the high dose was inhibitory. Spontaneous activity was only affected by the in vivo pretreatment with indomethacin, which prevented the decline in activity of scraped tissue with time.


2004 ◽  
Vol 96 (2) ◽  
pp. 784-791 ◽  
Author(s):  
Jay B. Dean ◽  
Daniel K. Mulkey ◽  
Richard A. Henderson ◽  
Stephanie J. Potter ◽  
Robert W. Putnam

Hyperoxia is a popular model of oxidative stress. However, hyperoxic gas mixtures are routinely used for chemical denervation of peripheral O2 receptors in in vivo studies of respiratory control. The underlying assumption whenever using hyperoxia is that there are no direct effects of molecular O2 and reactive O2 species (ROS) on brain stem function. In addition, control superfusates used routinely for in vitro studies of neurons in brain slices are, in fact, hyperoxic. Again, the assumption is that there are no direct effects of O2 and ROS on neuronal activity. Research contradicts this assumption by demonstrating that O2 has central effects on the brain stem respiratory centers and several effects on neurons in respiratory control areas; these need to be considered whenever hyperoxia is used. This mini-review summarizes the long-recognized, but seldom acknowledged, paradox of respiratory control known as hyperoxic hyperventilation. Several proposed mechanisms are discussed, including the recent hypothesis that hyperoxic hyperventilation is initiated by increased production of ROS during hyperoxia, which directly stimulates central CO2 chemoreceptors in the solitary complex. Hyperoxic hyperventilation may provide clues into the fundamental role of redox signaling and ROS in central control of breathing; moreover, oxidative stress may play a role in respiratory control dysfunction. The practical implications of brain stem O2 and ROS sensitivity are also considered relative to the present uses of hyperoxia in respiratory control research in humans, animals, and brain stem tissues. Recommendations for future research are also proposed.


1997 ◽  
Vol 83 (2) ◽  
pp. 170-176 ◽  
Author(s):  
Mineko Shibayama ◽  
Fernando Navarro-García ◽  
Rubén López-Revilla ◽  
Adolfo Martínez-Palomo ◽  
Víctor Tsutsumi

2020 ◽  
Author(s):  
Jinghong Chen ◽  
Ying Sun ◽  
Jinbao Wei ◽  
Peijun Ju ◽  
Qinjie Li ◽  
...  

Abstract Background: Visceral pain is one of the most common sign of irritable bowel syndrome (IBS). Chronic stress during pregnancy may increase visceral pain sensitivity of offspring in a sexdependent way. Combining adult stress in offspring will increase this sensitivity. Based on the evidence implicating estrogen exacerbates visceral hypersensitivity in female rodents in pre-clinical models, we predicted that chronic prenatal stress (CPS) plus chronic adult stress (CAS) will maximize visceral pain sensitivity; and estrogen plays an important role in this hyperalgesia.Methods: The CPS plus CAS rodent model was established in which the balloon was used to distend colorectum. Meanwhile, the single fiber recording in vivo and patch-clamp experiments in vitro were used to monitor neuronal activity. The RT-PCR, Western Blot, and Immunofluorescence were used to study the effects of CPS and CAS on colon primary afferent sensitivity and molecular or transmission changes. We use Ovariectomy and Letrozole to treate female rats respectively in order to assess the role of estrogen in female-specific enhanced primary afferent sensitization. Letrozole mainly used to reduce estrogen levels.Results: As predicted, CPS significantly increased single unit afferent fiber activity in L6-S2 dorsal roots in response. Activity was further enhanced by CAS. And the activity in offspring females was significantly greater than the males. Besides, the excitability of colon-projecting dorsal root ganglion (DRG) neurons increases in CPS + CAS rats that was associated with a decrease in transient A-type K+ current. Letrozole treatment decreases the colon DRG neuron excitability in females by decreasing the estrogen levels. Conclusions: This study adds to the growing evidence for the development of chronic stress induced visceral hypersensitivity in female, which involves estrogen-dependent sensitization of primary afferent colon neurons. Understanding this neurophysiological mechanisms will spur the development of female pain specific therapies.


2021 ◽  
Vol 15 ◽  
Author(s):  
Nihaad Paraouty ◽  
Todd M. Mowery

The corticostriatal circuit has been identified as a vital pathway for associative learning. However, how learning is implemented when the sensory striatum is permanently impaired remains unclear. Using chemogenetic techniques to suppress layer five auditory cortex (AC) input to the auditory striatum, learning of a sound discrimination task was significantly impacted in freely moving Mongolian gerbils, in particular when this suppression occurs early on during learning. Whole-cell recordings sampled throughout learning revealed a transient reduction in postsynaptic (GABAA) inhibition in both striatal D1 and D2 cells in normal-hearing gerbils during task acquisition. In contrast, when the baseline striatal inhibitory strengths and firing rates were permanently reduced by a transient period of developmental sensory deprivation, learning was accompanied by augmented inhibition and increased firing rates. Direct manipulation of striatal inhibition in vivo and in vitro revealed a key role of the transient inhibitory changes in task acquisition. Together, these results reveal a flexible corticostriatal inhibitory synaptic plasticity mechanism that accompanies associative auditory learning.


2011 ◽  
Vol 2011 ◽  
pp. 1-5
Author(s):  
Masana Yamada ◽  
Rika Sasaki ◽  
Koki Hirota ◽  
Mitsuaki Yamazaki

In order to investigate whether dementia modifies the anesthetic actions in the central nervous systems, we have studied effects of general anesthetics on the hippocampal synaptic transmission using the dementia model mice. Preliminary in vivo experiments revealed that time of loss of righting reflex following sevoflurane inhalation was more shortened in dementia mice than in healthy control mice. Field population spikes of hippocampal CA1 pyramidal neurons were elicited in vitro using orthodromic stimulation of Schaffer collateral commissural fibers (test pulse). The recurrent inhibition was enhanced with the second stimulating electrode placed in alveus hippocampi (prepulse) to activate recurrent inhibition of CA1. The prepulses were applied as train stimuli to activate release and then deplete γ-amino-butyric acid (GABA) at presynaptic terminals of inhibitory interneurons. Sevoflurane and thiopental had greater actions on inhibitory synaptic transmission in dementia model mice than in control mice. The pre-pulse train protocol revealed that the anesthetic-induced GABA discharge was more enhanced in dementia mice than in control mice. Dementia enhances the actions of general anesthetics due to the increase in GABA release from presynaptic terminals.


1995 ◽  
Vol 74 (6) ◽  
pp. 2604-2613 ◽  
Author(s):  
G. E. Spencer ◽  
N. I. Syed ◽  
K. Lukowiak ◽  
W. Winlow

1. In the present study we tested the ability of the general anesthetic, halothane, to affect synaptic transmission at in vivo and in vitro reconstructed peptidergic synapses between identified neurons of Lymnaea stagnalis. 2. An identified respiratory interneuron, visceral dorsal 4 (VD4), innervates a number of postsynaptic cells in the central ring ganglia of Lymnaea. Because VD4 has previously been shown to exhibit immunoreactivity for FMRFamide-related peptides, it was hypothesized that these peptides may be utilized by VD4 during synaptic transmission. In the intact, isolated CNS of Lymnaea, we have identified novel connections between VD4 and the pedal A (PeA) cells. We demonstrate that VD4 makes inhibitory connections with the PeA neurons, in particular PeA4, and that these synaptic responses are mimicked by exogenous application of FMRFamide. 3. The synaptic transmission between VD4 and the PeA cells in an intact, isolated CNS preparation was completely blocked in 2%, but not 1% halothanc. Interestingly, the postsynaptic responses (PeA) to exogenous FMRFamide were maintained in the presence of both 1 and 2% halothane. 4. To determine the specificity of the observed responses and to determine the precise synaptic site of anesthetic action, we reconstructed the VD4/PeA synapses in vitro. After isolation from their respective ganglia, both cell types extended processes and established neuritic contact. We demonstrated that not only did the presynaptic neuron reestablish the appropriate inhibitory synapses with the PeA neurons, but that the PeA cells also maintained their responsiveness to exogenous FMRFamide. 5. Superfusion of the in vitro synaptically connected VD4 and PeA cells with 2% halothane completely abolished the synaptic transmission between these cells. However, even higher concentrations of 4% halothane failed to block the responsiveness of the PeA neurons to exogenous FMRFamide. Moreover, both 1 and 2% halothane enhanced the duration of the postsynaptic response to exogenously applied FMRFamide. These data suggest that the halothane-induced depression of synaptic transmission most likely occurred at the presynaptic level. 6. This study provides the first direct evidence that peptidergic transmission in the nervous system may also be susceptible to the actions of general anesthetics. In addition, we utilized a novel approach of in vitro reconstructed synapses for studying the effects of general anesthetics on monosynaptic transmission in the absence of other synaptic influences.


2003 ◽  
Vol 90 (4) ◽  
pp. 2253-2260 ◽  
Author(s):  
Zhouyan Feng ◽  
Dominique M. Durand

It has been clearly established that nonsynaptic interactions are sufficient for generating epileptiform activity in brain slices. However, it is not known whether this type of epilepsy model can be generated in vivo. In this paper we investigate low-calcium nonsynaptic epileptiform activity in an intact hippocampus. The calcium chelator EGTA was used to lower [Ca2+]o in the hippocampus of urethane anesthetized rats. Spontaneous and evoked field potentials in CA1 pyramidal stratum and in CA1 stratum radiatum were recorded using four-channel silicon recording probes. Three different types of epileptic activity were observed while synaptic transmission was gradually blocked by a decline in hippocampal [Ca2+]o. A short latency burst, named early-burst, occurred during the early period of EGTA application. Periodic slow-waves and a long latency high-frequency burst, named late-burst, were seen after synaptic transmission was mostly blocked. Therefore these activities appear to be associated with nonsynaptic mechanisms. Moreover, the slow-waves were similar in appearance to the depolarization potential shifts in vitro with low calcium. In addition, excitatory postsynaptic amino acid antagonists could not eliminate the development of slow-waves and late-bursts. The slow-waves and late-bursts were morphologically similar to electrographic seizure activity seen in patients with temporal lobe epilepsy. These results clearly show that epileptic activity can be generated in vivo in the absence of synaptic transmission. This type of low-calcium nonsynaptic epilepsy model in an intact hippocampus could play an important role in revealing additional mechanisms of epilepsy disorders and in developing novel anti-convulsant drugs.


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