Role of Synaptic Inhibition in the Coupling of the Respiratory Rhythms that Underlie Eupnea and Sigh Behaviors

ABSTRACTThe preBötzinger Complex (preBötC) gives rise to two types of breathing behavior: eupnea and sighing. Here, we examine the neural mechanisms that couple their underlying rhythms by recording from the preBötC in neonatal mouse brainstem slice preparations. It has been proposed that chloride-mediated synaptic inhibition couples inspiratory (eupnea-related) bursts and sigh bursts, but we find no evidence to support that notion. First, we characterize a fluctuating temporal relationship between sigh bursts and their preceding inspiratory bursts; their coupling is far weaker than previously described. Surprisingly, selective blockade of inhibitory synapses strengthened (rather than weakened) that phasic inspiratory-sigh burst relationship. Furthermore, pharmacological disinhibition did not alter the duration of the prolonged interval that follows a sigh burst prior to resumption of the inspiratory rhythm. These results demonstrate that coupling between inspiratory and sigh rhythms does not depend on synaptic inhibition.SIGNIFICANCE STATEMENTBreathing consists of eupnea and sigh breaths, which differ in their magnitude and frequency. Both breath types emerge from a brainstem microcircuit that coordinates their timing. Here, we advance understanding of these rhythms by assessing the nature and strength of their coordination, and by showing that synaptic inhibition does not enforce their temporal coupling in contrast to conventional understanding. This study provides insights into the basic neural mechanisms that link oscillations of different amplitude and frequency in a core oscillator.

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

Molecular and Cellular Biology ◽

10.1128/mcb.13.3.1363 ◽

1993 ◽

Vol 13 (3) ◽

pp. 1363-1370 ◽

Cited By ~ 31

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.

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

Frontiers in Cellular Neuroscience ◽

10.3389/fncel.2021.817013 ◽

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.

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Role of Synaptic Inhibition in Synchronization of Thalamocortical Activity

Progress in Brain Research - Brain Reflexes, Proceedings of the International Conference dedicated to the centenary celebration of the publication of I. M. Sechenov's book Brain Reflexes ◽

10.1016/s0079-6123(08)63499-8 ◽

1968 ◽

pp. 107-122 ◽

Cited By ~ 8

Author(s):

DominickP. Purpura

Keyword(s):

Synaptic Inhibition

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

Journal of Neurophysiology ◽

10.1152/jn.00101.2018 ◽

2018 ◽

Vol 119 (6) ◽

pp. 2373-2379 ◽

Cited By ~ 2

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.

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

10.1101/414847 ◽

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.

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Role of the Telencephalon in the Synchronization of Locomotor and Respiratory Frequencies During Walking in Canada Geese

Journal of Experimental Biology ◽

10.1242/jeb.145.1.283 ◽

1989 ◽

Vol 145 (1) ◽

pp. 283-301 ◽

Cited By ~ 1

Author(s):

GREGORY D. FUNK ◽

WILLIAM MILSOM ◽

GERALD N. SHOLOMENKO ◽

JOHN D. STEEVES

Keyword(s):

Oxygen Uptake ◽

Minute Ventilation ◽

Work Rate ◽

Canada Geese ◽

Breathing Frequency ◽

Medullary Reticular Formation ◽

Co2 Output ◽

The Relationship ◽

Respiratory Rhythms

To elucidate the importance of telencephalic structures and the effects of metabolic rate in the production of locomotor-respiratory coupling, we examined the relationship between locomotor and ventilatory patterns in: (1) intact trained geese, and (2) brainstem-stimulated (medullary reticular formation) decerebrate geese, that were walking on a treadmill. The decerebrate geese, however, were not completely self supporting. Thus, while the two groups walked with similar stride frequencies (fs), they did so at two different work rates. While at rest, tidal volume (VT), breathing frequency (fv) and minute ventilation (VE) were very similar in the two groups. VE increased 120% during walking in the intact geese, primarily as a result of increases VE, while both VT and fv increased to produce a smaller 40 % increase in VE in the decerebrate birds. Although the magnitude of the increase in VE was three times greater in the intact geese, the relationships between VE and oxygen uptake (VO2) and VE and CO2 output (VCOCO2) were similar in the two groups. Significant coupling between locomotor and respiratory patterns was found in both intact (28.3%) and decerebrate birds (28.9%), suggesting that the telencephalon is not essential for the coupling of locomotor and respiratory rhythms during walking in geese. In addition, the incidence of locomotor-respiratory synchrony was virtually identical in the two groups in spite of a threefold difference in metabolic work rate.

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