Early postnatal maturation of GABA<sub>A</sub>‐mediated inhibition in the brainstem respiratory rhythm‐generating network of the mouse

Ritter, Barbara; Zhang, W.

doi:10.1046/j.1460-9568.2000.00152.x

Cited by 104 publications

(107 citation statements)

References 37 publications

Supporting

Mentioning

102

Contrasting

Order By: Relevance

“…Rather, it has been reported that the GABA A -mediated response switches from depolarization to hyperpolarization during the first postnatal week (Ritter and Zhang, 2000). However, the present results demonstrated the existence of inhibitory neural activity in the facial nucleus bilaterally in the wild-type E18.5 fetus under adrenaline-stimulated condition (Fig.…”

contrasting

confidence: 72%

Malfunction of Respiratory-Related Neuronal Activity in Na⁺, K⁺-ATPase α2 Subunit-Deficient Mice Is Attributable to Abnormal Cl^-Homeostasis in Brainstem Neurons

et al. 2004

View full text Add to dashboard Cite

show abstract

contrasting

confidence: 72%

Malfunction of Respiratory-Related Neuronal Activity in Na⁺, K⁺-ATPase α2 Subunit-Deficient Mice Is Attributable to Abnormal Cl^-Homeostasis in Brainstem Neurons

et al. 2004

View full text Add to dashboard Cite

show abstract

“…Glutamatergic transmission is obligatory for rhythmogenesis in vitro (26,27), whereas inhibitory transmission is not (28,29). Synaptic inhibition nonetheless regulates the amplitude of XII motor output (10,11). To focus on the role of glutamatergic neurons, we performed these experiments in the presence of picrotoxin and strychnine.…”

Section: Discussionmentioning

confidence: 99%

“…We were able to image to a depth of 80 μm by using Ti:sapphire laser pulses in both slice types. Synaptic inhibition is not essential for rhythmogenesis in vitro, but it influences the amplitude of XII output (10,11). Therefore, we added 5 μM strychnine and picrotoxin to the artificial cerebrospinal fluid (ACSF) before the detection phase so that XII output would be insensitive to the effects of laser-ablating inhibitory neurons (12,13) during the ablation phase.…”

Section: Detecting Inspiratory Neurons In the Prebötc And Ventral Resmentioning

confidence: 99%

Cumulative lesioning of respiratory interneurons disrupts and precludes motor rhythms in vitro

Hayes

Wang²,

Negro³

2012

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

How brain functions degenerate in the face of progressive cell loss is an important issue that pertains to neurodegenerative diseases and basic properties of neural networks. We developed an automated system that uses two-photon microscopy to detect rhythmic neurons from calcium activity, and then individually laser ablates the targets while monitoring network function in real time. We applied this system to the mammalian respiratory oscillator located in the pre-Bötzinger Complex (preBötC) of the ventral medulla, which spontaneously generates breathing-related motor activity in vitro. Here, we show that cumulatively deleting preBötC neurons progressively decreases respiratory frequency and the amplitude of motor output. On average, the deletion of 120 ± 45 neurons stopped spontaneous respiratory rhythm, and our data suggest ≈82% of the rhythm-generating neurons remain unlesioned. Cumulative ablations in other medullary respiratory regions did not affect frequency but diminished the amplitude of motor output to a lesser degree. These results suggest that the preBötC can sustain insults that destroy no more than ≈18% of its constituent interneurons, which may have implications for the onset of respiratory pathologies in disease states.central pattern generator | calcium imaging | brainstem C entral pattern generator (CPG) networks produce coordinated motor patterns that underlie behaviors such as breathing, locomotion, and chewing (1, 2). A key issue is not just which cell types generate these patterns of activity, but how many? This question pertains to whether and how cumulative cell loss will impair and, possibly preclude, network function.Breathing consists of inspiratory and expiratory phases. The preBötzinger Complex (preBötC) of the medulla putatively contains the inspiratory CPG (3, 4). Over several days in vivo, saporinmediated destruction of preBötC neurons that express neurokinin-1 receptors (NK1Rs) causes sleep-disordered breathing and fatal respiratory pathology (5, 6). Similarly, acute cell-silencing of a subset of the same NK1R-expressing population of preBötC neurons stops spontaneous breathing in awake adult rats (7). These studies helped to determine the cellular composition of the preBötC and confirmed that it was essential for breathing in an otherwise intact animal, but could not measure the resiliency of the preBötC when faced with silencing or deleting its core piecewise.We examined this issue by using slice preparations that capture the preBötC and spontaneously generate fictive breathing-related activity in vitro. We developed a computer-automated system that detects rhythmically active interneurons via two-photon calcium imaging, stores their physical locations in memory, and then laser ablates the targets sequentially, while electrophysiologically monitoring the motor output of the circuit. We applied this system to the preBötC to test the hypothesis that piecewise destruction of the CPG core would cause graded loss of motor activity up to rhythm cessation. We surmised that this effect ...

show abstract

“…natal maturation of GABAergic inhibitory transmission (Ritter and Zhang, 2000). First, we have identified a bilateral rhythm generation site spatially restricted in a region ventral to the nucleus ambiguus, the activity of which is preserved in a transverse slice (Smith et al, 1991).…”

Section: The Hf Generator Is the Respiratory Generatormentioning

confidence: 99%

Emergence of the Pre-Bötzinger Respiratory Rhythm Generator in the Mouse Embryo

Thoby‐Brisson¹,

Trinh²,

Champagnat³

et al. 2005

J. Neurosci.

117

148

View full text Add to dashboard Cite

To obtain insights into the emergence of rhythmogenic circuits supporting respiration, we monitored spontaneous activities in isolated brainstem and medullary transverse slice preparations of mouse embryos, combining electrophysiological and calcium imaging techniques. At embryonic day 15 (E15), in a restricted region ventral to the nucleus ambiguus, we observed the onset of a sustained highfrequency (HF) respiratory-like activity in addition to a preexisting low-frequency activity having a distinct initiation site, spatial extension, and susceptibility to gap junction blockers. At the time of its onset, the HF generator starts to express the neurokinin 1 receptor, is connected bilaterally, requires active AMPA/kainate glutamatergic synapses, and is modulated by substance P and the -opioid agonist D-Ala 2 -N-Me-Phe 4 -Glycol 5 -enkephalin. We conclude that a rhythm generator sharing the properties of the neonatal pre-Bötzinger complex becomes active during E15 in mice.

show abstract

Early postnatal maturation of GABA_A‐mediated inhibition in the brainstem respiratory rhythm‐generating network of the mouse

Cited by 104 publications

References 37 publications

Malfunction of Respiratory-Related Neuronal Activity in Na⁺, K⁺-ATPase α2 Subunit-Deficient Mice Is Attributable to Abnormal Cl^-Homeostasis in Brainstem Neurons

Malfunction of Respiratory-Related Neuronal Activity in Na⁺, K⁺-ATPase α2 Subunit-Deficient Mice Is Attributable to Abnormal Cl^-Homeostasis in Brainstem Neurons

Cumulative lesioning of respiratory interneurons disrupts and precludes motor rhythms in vitro

Emergence of the Pre-Bötzinger Respiratory Rhythm Generator in the Mouse Embryo

Contact Info

Product

Resources

About

Early postnatal maturation of GABAA‐mediated inhibition in the brainstem respiratory rhythm‐generating network of the mouse

Cited by 104 publications

References 37 publications

Malfunction of Respiratory-Related Neuronal Activity in Na+, K+-ATPase α2 Subunit-Deficient Mice Is Attributable to Abnormal Cl-Homeostasis in Brainstem Neurons

Malfunction of Respiratory-Related Neuronal Activity in Na+, K+-ATPase α2 Subunit-Deficient Mice Is Attributable to Abnormal Cl-Homeostasis in Brainstem Neurons

Cumulative lesioning of respiratory interneurons disrupts and precludes motor rhythms in vitro

Emergence of the Pre-Bötzinger Respiratory Rhythm Generator in the Mouse Embryo

Contact Info

Product

Resources

About

Early postnatal maturation of GABA_A‐mediated inhibition in the brainstem respiratory rhythm‐generating network of the mouse

Malfunction of Respiratory-Related Neuronal Activity in Na⁺, K⁺-ATPase α2 Subunit-Deficient Mice Is Attributable to Abnormal Cl^-Homeostasis in Brainstem Neurons

Malfunction of Respiratory-Related Neuronal Activity in Na⁺, K⁺-ATPase α2 Subunit-Deficient Mice Is Attributable to Abnormal Cl^-Homeostasis in Brainstem Neurons