The Midbrain Periaqueductal Gray Control of Respiration

Subramanian, Hari H.; Balnave, Ron J.; Holstege, Gert

doi:10.1523/jneurosci.4168-08.2008

Cited by 135 publications

(190 citation statements)

References 43 publications

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“…NRA stimulation 1-3 mm caudal to the obex Microinjections (DLH, 200 mM, 10 nl; n ϭ 12) in the NRA 1-3 mm caudal to the obex produced vocalization, which lasted between 20 and 90 s. This vocalization cannot be described as mews, howls or hisses, as is the case with the DLH stimulation in the PAG (Subramanian et al, 2008) but a totally different subdued guttural sound. During this typical vocalization (Fig.…”

Section: Resultsmentioning

confidence: 96%

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The Nucleus Retroambiguus Control of Respiration

Subramanian¹,

Holstege²

2009

J. Neurosci.

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The role of the nucleus retroambiguus (NRA) in the context of respiration control has been subject of debate for considerable time. To solve this problem, we chemically (using D, L-homocysteic acid) stimulated the NRA in unanesthetized precollicularly decerebrated cats and studied the respiratory effect via simultaneous measurement of tracheal pressure and electromyograms of diaphragm, internal intercostal (IIC), cricothyroid (CT), and external oblique abdominal (EO) muscles. NRA-stimulation 0 -1 mm caudal to the obex resulted in recruitment of IIC muscle and reduction in respiratory frequency. NRA-stimulation 1-3 mm caudal to the obex produced vocalization along with CT activation and slight increase in tracheal pressure, but no change in respiratory frequency. NRA-stimulation 3-5 mm caudal to the obex produced CT muscle activation and an increase in respiratory frequency, but no vocalization. NRA-stimulation 5-8 mm caudal to the obex produced EO muscle activation and reduction in respiratory frequency. A change to the inspiratory effort was never observed, regardless of which NRA part was stimulated. The results demonstrate that NRA does not control eupneic inspiration but consists of topographically separate groups of premotor interneurons each producing detailed motor actions. These motor activities have in common that they require changes to eupneic breathing. Different combination of activation of these premotor neurons determines the final outcome, e.g., vocalization, vomiting, coughing, sneezing, mating posture, or child delivery. Higher brainstem regions such as the midbrain periaqueductal gray (PAG) decides which combination of NRA neurons are excited. In simple terms, the NRA is the piano, the PAG one of the piano players.

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Section: Resultsmentioning

confidence: 96%

“…The raw diaphragm EMG signal was used for measurement of Ti and Te. This method is extensively described in our previous study (Subramanian et al, 2008). Significant differences between the mean values were detected using Scheffe least difference test and a probability of p Ͻ 0.05 was considered significant.…”

Section: Methodsmentioning

confidence: 99%

The Nucleus Retroambiguus Control of Respiration

Subramanian¹,

Holstege²

2009

J. Neurosci.

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“…Rather, these simulated patterns constitute low amplitude events that may seed burstlets and preinspiratory activity (29). Another important feature of the preBötC network is its rapid responsiveness to phasic inputs from central or peripheral (reflex) origins (30)(31)(32). Therefore, we sought to evaluate the minimal number of concurrently active neurons necessary for initiating a preBötC network response.…”

Section: Rhythmic Activity Depends On the Number And Strength Of Connmentioning

confidence: 99%

Robust network oscillations during mammalian respiratory rhythm generation driven by synaptic dynamics

Guerrier

Hayes

Fortin

et al. 2015

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

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How might synaptic dynamics generate synchronous oscillations in neuronal networks? We address this question in the preBötzinger complex (preBötC), a brainstem neural network that paces robust, yet labile, inspiration in mammals. The preBötC is composed of a few hundred neurons that alternate bursting activity with silent periods, but the mechanism underlying this vital rhythm remains elusive. Using a computational approach to model a randomly connected neuronal network that relies on short-term synaptic facilitation (SF) and depression (SD), we show that synaptic fluctuations can initiate population activities through recurrent excitation. We also show that a two-step SD process allows activity in the network to synchronize (bursts) and generate a population refractory period (silence). The model was validated against an array of experimental conditions, which recapitulate several processes the preBötC may experience. Consistent with the modeling assumptions, we reveal, by electrophysiological recordings, that SF/SD can occur at preBötC synapses on timescales that influence rhythmic population activity. We conclude that nondeterministic neuronal spiking and dynamic synaptic strengths in a randomly connected network are sufficient to give rise to regular respiratory-like rhythmic network activity and lability, which may play an important role in generating the rhythm for breathing and other coordinated motor activities in mammals.central pattern generator | synaptic depression | mathematical modeling | numerical simulations | breathing C entral pattern generators (CPGs) are neuronal circuits that generate coordinated activity in the absence of sensory input (1). One such mammalian CPG, the preBötzinger complex (preBötC), gives rise to the eupneic respiratory rhythm (2, 3). Located in the medulla, the preBötC preserves a spontaneous respiratory-like rhythm when isolated in transverse slices, but the precise nature of the cellular and synaptic mechanisms underlying rhythmogenesis remains elusive (3-7). An early hypothesis was that the neuronal activity is driven by intrinsically bursting pacemaker neurons synchronized via excitatory synaptic connections (2,6,8,9). However, electrophysiological and modeling studies (7, 10-12) now suggest the rhythm emerges through stochastic activation of intrinsic currents conveyed by recurrent synaptic connections, without the need for pacemaker neurons (3,4,11,13,14). In either case, excitatory synapses are required for rhythm generation; the possibility that synaptic properties also underlie periodic burst initiation and termination is yet to be demonstrated.Synaptic transmission relies on the release of vesicles, which can be modulated at the presynaptic terminal. Synaptic depression (SD), based on vesicular release, consists of decaying release probability after sustained activity, which subsequently decreases excitability within the underlying connected network. Conversely, synaptic facilitation (SF) enhances vesicular release probability and promotes neuronal synchronizatio...

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“…Similarly, volitional inspiration activates more respiratory-related cortical and subcortical areas when compared to volitional expiration 46 . These cortical and subcortical areas activated during voluntary breathing are also involved in different functions 53 , such as muscle tone, pain, posture, mood, speech, etc. Therefore, it is not unreasonable to associate interactions in breathing with modulation of other functions.…”

Section: Chae and Yumentioning

confidence: 99%

Breathing-controlled Electrical Stimulation (BreEStim) for Management of Neuropathic Pain and Spasticity

2013

JoVE

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Electrical stimulation (EStim) refers to the application of electrical current to muscles or nerves in order to achieve functional and therapeutic goals. It has been extensively used in various clinical settings. Based upon recent discoveries related to the systemic effects of voluntary breathing and intrinsic physiological interactions among systems during voluntary breathing, a new EStim protocol, Breathing-controlled Electrical Stimulation (BreEStim), has been developed to augment the effects of electrical stimulation. In BreEStim, a single-pulse electrical stimulus is triggered and delivered to the target area when the airflow rate of an isolated voluntary inspiration reaches the threshold. BreEStim integrates intrinsic physiological interactions that are activated during voluntary breathing and has demonstrated excellent clinical efficacy. Two representative applications of BreEStim are reported with detailed protocols: management of post-stroke finger flexor spasticity and neuropathic pain in spinal cord injury.

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The Midbrain Periaqueductal Gray Control of Respiration

Cited by 135 publications

References 43 publications

The Nucleus Retroambiguus Control of Respiration

The Nucleus Retroambiguus Control of Respiration

Robust network oscillations during mammalian respiratory rhythm generation driven by synaptic dynamics

Breathing-controlled Electrical Stimulation (BreEStim) for Management of Neuropathic Pain and Spasticity

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