scholarly journals Role of synaptic inhibition in the coupling of the respiratory rhythms that underlie eupnea and sigh behaviors

2019 ◽  
Author(s):  
Daniel S. Borrus ◽  
Gregory D. Conradi Smith ◽  
Christopher A. Del Negro
Keyword(s):  
Temporal Relationship ◽  
Neonatal Mouse ◽  
Neural Mechanisms ◽  
Inhibitory Synapses ◽  
Synaptic Inhibition ◽  
Selective Blockade ◽  
Brainstem Slice ◽  
Temporal Coupling ◽  
Respiratory Rhythms

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.

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

eNeuro ◽  
2020 ◽  
Vol 7 (3) ◽  
pp. ENEURO.0302-19.2020
Author(s):  
Daniel S. Borrus ◽  
Cameron J. Grover ◽  
Gregory D. Conradi Smith ◽  
Christopher A. Del Negro
Keyword(s):  
Synaptic Inhibition ◽  
Respiratory Rhythms

The role of GABAA receptor biogenesis, structure and function in epilepsy

2006 ◽  
Vol 34 (5) ◽  
pp. 863-867 ◽  
Author(s):  
S. Mizielinska ◽  
S. Greenwood ◽  
C.N. Connolly
Keyword(s):  
Gabaa Receptor ◽  
Structure And Function ◽  
Inhibitory Synapses ◽  
Normal Brain ◽  
Synaptic Targeting ◽  
Acid Type ◽  
Normal Brain Function ◽  
And Function ◽  
The Brain

Maintaining the correct balance in neuronal activation is of paramount importance to normal brain function. Imbalances due to changes in excitation or inhibition can lead to a variety of disorders ranging from the clinically extreme (e.g. epilepsy) to the more subtle (e.g. anxiety). In the brain, the most common inhibitory synapses are regulated by GABAA (γ-aminobutyric acid type A) receptors, a role commensurate with their importance as therapeutic targets. Remarkably, we still know relatively little about GABAA receptor biogenesis. Receptors are constructed as pentameric ion channels, with α and β subunits being the minimal requirement, and the incorporation of a γ subunit being necessary for benzodiazepine modulation and synaptic targeting. Insights have been provided by the discovery of several specific assembly signals within different GABAA receptor subunits. Moreover, a number of recent studies on GABAA receptor mutations associated with epilepsy have further enhanced our understanding of GABAA receptor biogenesis, structure and function.

Repetition Suppression of Induced Gamma Activity Predicts Enhanced Orienting toward a Novel Stimulus in 6-month-old Infants

2008 ◽  
Vol 20 (12) ◽  
pp. 2137-2152 ◽  
Author(s):  
Kelly A. Snyder ◽  
Andreas Keil
Keyword(s):  
Visual Processing ◽  
Novelty Detection ◽  
Neural Mechanisms ◽  
Human Infant ◽  
Gamma Activity ◽  
Repeated Stimulus ◽  
Repetition Suppression ◽  
The Face ◽  
Over 40 Years

Habituation refers to a decline in orienting or responding to a repeated stimulus, and can be inferred to reflect learning about the properties of the repeated stimulus when followed by increased orienting to a novel stimulus (i.e., novelty detection). Habituation and novelty detection paradigms have been used for over 40 years to study perceptual and mnemonic processes in the human infant, yet important questions remain about the nature of these processes in infants. The aim of the present study was to examine the neural mechanisms underlying habituation and novelty detection in infants. Specifically, we investigated changes in induced alpha, beta, and gamma activity in 6-month-old infants during repeated presentations of either a face or an object, and examined whether these changes predicted behavioral responses to novelty at test. We found that induced gamma activity over occipital scalp regions decreased with stimulus repetition in the face condition but not in the toy condition, and that greater decreases in the gamma band were associated with enhanced orienting to a novel face at test. The pattern and topography of these findings are consistent with observations of repetition suppression in the occipital–temporal visual processing pathway, and suggest that encoding in infant habituation paradigms may reflect a form of perceptual learning. Implications for the role of repetition suppression in infant habituation and novelty detection are discussed with respect to a biased competition model of visual attention.

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.

Intra-arterial instillation of a nociceptive agent modulate cardiorespiratory parameters involving 5-HT3 and TRPV1 receptors in anesthetized rats

2021 ◽  
Vol 21 ◽  
Author(s):  
Sanjeev K. Singh ◽  
M. S. Muthu ◽  
Ravindran Revand ◽  
M. B. Mandal
Keyword(s):  
Transient Receptor Potential ◽  
Sensory Nerve ◽  
Receptor Potential ◽  
Neural Mechanisms ◽  
Transient Receptor Potential Vanilloid ◽  
Anesthetized Rats ◽  
Trpv1 Receptors ◽  
Perivascular Nerves ◽  
Transient Receptor

Background: Since long back, it has been a matter of discussion regarding the role of peripheral blood vessels in regulation of cardiorespiratory (CVR) system. Objective: The role of 5-HT3 and TRPV1 receptors present on perivascular nerves in elicitation of CVR reflexes was examined after intra-arterial instillation of bradykinin in urethane anesthetized rats. Materials and Methods: Femoral artery was cannulated retrogradely and was utilized for the instillation of saline/agonist/antagonist and recording of blood pressure (BP), using a double ported 24G cannula. BP, respiration and ECG were recorded for 30 min after bradykinin (1 µM) in the absence or presence of antagonists. Results: Instillation of bradykinin produced immediate hypotensive (40%), bradycardiac (17%), tachypnoeic (45%) and hyperventilatory (96%) responses of shorter latencies (5-8 s) favoring the neural mechanisms in producing the responses. In lignocaine (2%) pretreated animals, bradykinin-induced hypotensive (10%), bradycardiac (1.7%), tachypnoeic (13%) and hyperventilatory (13%) responses attenuated significantly. Pretreatment with ondansetron (100 µg/kg), 5-HT3-antagonist attenuated the hypotensive (10%), bradycardiac (1.7%), tachypnoeic (11%) and hyperventilatory (11%) responses significantly. Pretreatment with capsazepine (1 mg/kg), transient receptor potential vanilloid 1- antagonist blocked the hypotensive (5%), bradycardiac (1.2%), tachypnoeic (6%) and hyperventilatory (6%) responses significantly. Conclusion: In conclusion, presence of a nociceptive agent in the local segment of an artery evokes vasosensory reflex responses modulating CVR parameters involving TRPV1 and 5-HT3 receptors present on the perivascular sensory nerve terminals in anesthetized rats.

scholarly journals Neural mechanisms of extinguishing drug and pleasant cue associations in human addiction: role of the VMPFC

2017 ◽  
Vol 24 (1) ◽  
pp. 88-99 ◽  
Author(s):  
Anna B. Konova ◽  
Muhammad A. Parvaz ◽  
Vladimir Bernstein ◽  
Anna Zilverstand ◽  
Scott J. Moeller ◽  
...  
Keyword(s):  
Neural Mechanisms

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.

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