Release your inhibitions: The role of postinhibitory rebound and synaptic inhibition in the generation of expiratory activity

2021 ◽  
Author(s):  
Robert TR Huckstepp ◽  
Gregory D Funk
Keyword(s):  
Synaptic Inhibition ◽  
Postinhibitory Rebound

scholarly journals V(D)J recombination: signal and coding joint resolution are uncoupled and depend on parallel synapsis of the sites.

1993 ◽  
Vol 13 (3) ◽  
pp. 1363-1370 ◽  
Author(s):  
K M Sheehan ◽  
M R Lieber
Keyword(s):  
Genome Stability ◽  
Lymphoid Cells ◽  
Chromosomal Translocations ◽  
Synaptic Inhibition ◽  
Site Specific ◽  
Coding Sequences ◽  
Specific Process ◽  
A Site ◽  
Joint Resolution

V(D)J recombination in lymphoid cells is a site-specific process in which the activity of the recombinase enzyme is targeted to signal sequences flanking the coding elements of antigen receptor genes. The order of the steps in this reaction and their mechanistic interdependence are important to the understanding of how the reaction fails and thereby contributes to genomic instability in lymphoid cells. The products of the normal reaction are recombinant joints linking the coding sequences of the receptor genes and, reciprocally, the signal ends. Extrachromosomal substrate molecules were modified to inhibit the physical synapsis of the recombination signals. In this way, it has been possible to assess how inhibiting the formation of one joint affects the resolution efficiency of the other. Our results indicate that signal joint and coding joint formation are resolved independently in that they can be uncoupled from each other. We also find that signal synapsis is critical for the generation of recombinant products, which greatly restricts the degree of potential single-site cutting that might otherwise occur in the genome. Finally, inversion substrates manifest synaptic inhibition at much longer distances than do deletion substrates, suggesting that a parallel rather than an antiparallel alignment of the signals is required during synapsis. These observations are important for understanding the interaction of V(D)J signals with the recombinase. Moreover, the role of signal synapsis in regulating recombinase activity has significant implications for genome stability regarding the frequency of recombinase-mediated chromosomal translocations.

scholarly journals Striatal Chloride Dysregulation and Impaired GABAergic Signaling Due to Cation-Chloride Cotransporter Dysfunction in Huntington’s Disease

2022 ◽  
Vol 15 ◽  
Author(s):  
Melissa Serranilla ◽  
Melanie A. Woodin
Keyword(s):  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Neurological Disorders ◽  
Synaptic Inhibition ◽  
Motor Impairments ◽  
Immature Brain ◽  
Amino Butyric Acid ◽  
Mature Neurons ◽  
Cation Chloride Cotransporters

Intracellular chloride (Cl–) levels in mature neurons must be tightly regulated for the maintenance of fast synaptic inhibition. In the mature central nervous system (CNS), synaptic inhibition is primarily mediated by gamma-amino butyric acid (GABA), which binds to Cl– permeable GABAA receptors (GABAARs). The intracellular Cl– concentration is primarily maintained by the antagonistic actions of two cation-chloride cotransporters (CCCs): Cl–-importing Na+-K+-Cl– co-transporter-1 (NKCC1) and Cl– -exporting K+-Cl– co-transporter-2 (KCC2). In mature neurons in the healthy brain, KCC2 expression is higher than NKCC1, leading to lower levels of intracellular Cl–, and Cl– influx upon GABAAR activation. However, in neurons of the immature brain or in neurological disorders such as epilepsy and traumatic brain injury, impaired KCC2 function and/or enhanced NKCC1 expression lead to intracellular Cl– accumulation and GABA-mediated excitation. In Huntington’s disease (HD), KCC2- and NKCC1-mediated Cl–-regulation are also altered, which leads to GABA-mediated excitation and contributes to the development of cognitive and motor impairments. This review summarizes the role of Cl– (dys)regulation in the healthy and HD brain, with a focus on the basal ganglia (BG) circuitry and CCCs as potential therapeutic targets in the treatment of HD.

scholarly journals Learning-induced modulation of the effect of neuroglial transmission on synaptic plasticity

2018 ◽  
Vol 119 (6) ◽  
pp. 2373-2379 ◽  
Author(s):  
Luna Jammal ◽  
Ben Whalley ◽  
Edi Barkai
Keyword(s):  
Synaptic Transmission ◽  
Gap Junctions ◽  
Piriform Cortex ◽  
Rule Learning ◽  
Long Term Potentiation ◽  
Synaptic Inhibition ◽  
Term Potentiation ◽  
Term Maintenance

Training rats in a complex olfactory discrimination task results in acquisition of “rule learning” (learning how to learn), a term describing the capability to perform the task superbly. Such rule learning results in strengthening of both excitatory and inhibitory synaptic connections between neurons in the piriform cortex. Moreover, intrinsic excitability is also enhanced throughout the pyramidal neuron population. Surprisingly, the cortical network retains its stability under these long-term modifications. In particular, the susceptibility for long-term potentiation (LTP) induction, while decreased for a short time window, returns to almost its pretraining value, although significant strengthening of AMPA receptor-mediated glutamatergic transmission remains. Such network balance is essential for maintaining the single-cell modifications that underlie long-term memory while preventing hyperexcitability that would result in runaway synaptic activity. However, the mechanisms underlying the long-term maintenance of such balance have yet to be described. In this study, we explored the role of astrocyte-mediated gliotransmission in long-term maintenance of learning-induced modifications in susceptibility for LTP induction and control of the strength of synaptic inhibition. We show that blocking connexin 43 hemichannels, which form gap junctions between astrocytes, decreases significantly the ability to induce LTP by stimulating the excitatory connections between piriform cortex pyramidal neurons after learning only. In parallel, spontaneous miniature inhibitory postsynaptic current amplitude is reduced in neurons from trained rats only, to the level of prelearning. Thus gliotransmission has a key role in maintaining learning-induced cortical stability by a wide-ranged control on synaptic transmission and plasticity. NEW & NOTEWORTHY We explore the role of astrocyte-mediated gliotransmission in maintenance of olfactory discrimination learning-induced modifications. We show that blocking gap junctions between astrocytes decreases significantly the ability to induce long-term potentiation in the piriform cortex after learning only. In parallel, synaptic inhibition is reduced in neurons from trained rats only, to the level of prelearning. Thus gliotransmission has a key role in maintaining learning-induced cortical stability by a wide-ranged control on synaptic transmission and plasticity.

scholarly journals Cluster Burst Synchronization in A Scale-Free Network of Inhibitory Bursting Neurons

2018 ◽  
Author(s):  
Sang-Yoon Kim ◽  
Woochang Lim
Keyword(s):  
Coupling Strength ◽  
Synaptic Inhibition ◽  
Stochastic Noise ◽  
Scale Free Network ◽  
Scale Free ◽  
Bursting Neurons ◽  
Raster Plot ◽  
Free Network ◽  
Burst Synchronization

We consider a scale-free network of inhibitory Hindmarsh-Rose (HR) bursting neurons, and investigate coupling-induced cluster burst synchronization by varying the average coupling strength J0. For sufficiently small J0, non-cluster desynchronized states exist. However, when passing a critical point , the whole population is segregated into 3 clusters via a constructive role of synaptic inhibition to stimulate dynamical clustering between individual burstings, and thus 3-cluster desynchronized states appear. As J0 is further increased and passes a lower threshold , a transition to 3-cluster burst synchronization occurs due to another constructive role of synaptic inhibition to favor population synchronization. In this case, HR neurons in each cluster exhibit burst synchronization. However, as J0 passes an intermediate threshold , HR neurons begin to make intermittent hoppings between the 3 clusters. Due to the intermittent intercluster hoppings, the 3 clusters are integrated into a single one. In spite of break-up of the 3 clusters, (non-cluster) burst synchronization persists in the whole population, which is well visualized in the raster plot of burst onset times where bursting stripes (composed of burst onset times and indicating burst synchronization) appear successively. With further increase in J0, intercluster hoppings are intensified, and bursting stripes also become smeared more and more due to a destructive role of synaptic inhibition to spoil the burst synchronization. Eventually, when passing a higher threshold a transition to desynchronization occurs via complete overlap between the bursting stripes. Finally, we also investigate the effects of stochastic noise on both 3-cluster burst synchronization and intercluster hoppings.

scholarly journals Role of synaptic inhibition in turtle respiratory rhythm generation

2002 ◽  
Vol 544 (1) ◽  
pp. 253-265 ◽  
Author(s):  
Stephen M. Johnson ◽  
Julia E. R. Wilkerson ◽  
Michael R. Wenninger ◽  
Daniel R. Henderson ◽  
Gordon S. Mitchell
Keyword(s):  
Respiratory Rhythm ◽  
Synaptic Inhibition ◽  
Rhythm Generation ◽  
Respiratory Rhythm Generation

scholarly journals Correct CYFIP1 dosage is essential for synaptic inhibition and the excitatory/inhibitory balance.

2018 ◽  
Author(s):  
Elizabeth C Davenport ◽  
Blanka Szulc ◽  
James Drew ◽  
James Taylor ◽  
Toby Morgan ◽  
...  
Keyword(s):  
Opposite Effect ◽  
Copy Number Variations ◽  
Conditional Knockout ◽  
Inhibitory Synapses ◽  
Synaptic Inhibition ◽  
Postsynaptic Currents ◽  
Synaptic Structure ◽  
And Function

Altered excitatory/inhibitory balance is implicated in neuropsychiatric disorders but the genetic aetiology of this is still poorly understood. Copy number variations in CYFIP1 are associated with autism, schizophrenia and intellectual disability but the role of CYFIP1 in regulating synaptic inhibition or excitatory/inhibitory balance remains unclear. We show, CYFIP1, and its paralogue CYFIP2, are enriched at inhibitory postsynaptic sites. While upregulation of CYFIP1 or CYFIP2 increased excitatory synapse number and the frequency of miniature excitatory postsynaptic currents (mEPSCs), it had the opposite effect at inhibitory synapses, decreasing their size and the amplitude of miniature inhibitory postsynaptic currents (mIPSCs). Contrary to CYFIP1 upregulation, its loss in vivo, upon conditional knockout in neocortical principal cells, increased expression of postsynaptic GABA A receptor β2/3-subunits and neuroligin 3 and enhanced synaptic inhibition. Thus, CYFIP1 dosage can bi-directionally impact inhibitory synaptic structure and function, potentially leading to altered excitatory/inhibitory balance and circuit dysfunction in CYFIP1-associated neurodevelopmental disorders.

scholarly journals Disruption of KCC2 Reveals an Essential Role of K-Cl Cotransport Already in Early Synaptic Inhibition

Neuron ◽  
2001 ◽  
Vol 30 (2) ◽  
pp. 515-524 ◽  
Author(s):  
Christian A. Hübner ◽  
Valentin Stein ◽  
Irm Hermans-Borgmeyer ◽  
Torsten Meyer ◽  
Klaus Ballanyi ◽  
...  
Keyword(s):  
Essential Role ◽  
Synaptic Inhibition

Serine/Threonine Protein Phosphatases and Synaptic Inhibition Regulate the Expression of Cholinergic-Dependent Plateau Potentials

2001 ◽  
Vol 85 (3) ◽  
pp. 1197-1205 ◽  
Author(s):  
Douglas D. Fraser ◽  
Daniel Doll ◽  
Brian A. MacVicar
Keyword(s):  
Pyramidal Neurons ◽  
Protein Phosphatases ◽  
Cholinergic Receptor ◽  
Normal Activity ◽  
Receptor Subtypes ◽  
Synaptic Inhibition ◽  
Plateau Potentials ◽  
Cation Conductance ◽  
M3 Receptor

We previously identified cholinergic-dependent plateau potentials (PPs) in CA1 pyramidal neurons that were intrinsically generated by interplay between voltage-gated calcium entry and a Ca2+-activated nonselective cation conductance. In the present study, we examined both the second-messenger pathway and the role of synaptic inhibition in the expression of PPs. The stimulation of m1/m3 cholinergic receptor subtypes and G-proteins were critical for activating PPs because selective receptor antagonists (pirenzepine, hexahydro-sila-difenidol hydrochloride, 4-diphenylacetoxy- N-methylpiperidine methiodide) and intracellular guanosine-5′- O-(2-thiodiphosphate) prevented PP generation in carbachol. Intense synaptic stimulation occasionally activated PPs in the presence of oxytremorine M, a cholinergic agonist with preference for m1/m3 receptors. PPs were consistently activated by synaptic stimulation only when oxytremorine M was combined with antagonists at both GABAA and GABAB receptors. These latter data indicate an important role for synaptic inhibition in preventing PP generation. Both intrinsically generated and synaptically activated PPs could not be elicited following inhibition of serine/threonine protein phosphatases by calyculin A, okadaic acid, or microcystin-L, suggesting that muscarinic-induced dephosphorylation is necessary for PP generation. PP genesis was also inhibited following irreversible thiophosphorylation by intracellular perfusion with ATP-γ-S. These data indicate that the expression of cholinergic-dependent PPs requires protein phosphatase-induced dephosphorylation via G-protein–linked m1/m3 receptor(s). Moreover, synaptic inhibition via both GABAA and GABAB receptors normally prevents the synaptic activation of PPs. Understanding the regulation of PPs should provide clues to the role of this regenerative potential in both normal activity and pathophysiological processes such as epilepsy.

scholarly journals Role of Synaptic Inhibition in Processing of Dynamic Binaural Level Stimuli

1998 ◽  
Vol 18 (2) ◽  
pp. 794-803 ◽  
Author(s):  
Dan H. Sanes ◽  
Brian J. Malone ◽  
Malcolm N. Semple
Keyword(s):  
Synaptic Inhibition
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