Projections from the mesopontine tegmental anesthesia area to regions involved in pain modulation

Sukhotinsky, Inna; Reiner, K.; Govrin-Lippmann, Ruth; Belenky, Michael; Lü, Jun; Hopkins, David A.; Saper, Clifford B.; Devor, Marshall

doi:10.1016/j.jchemneu.2006.08.003

Cited by 26 publications

(18 citation statements)

References 95 publications

(118 reference statements)

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“…A few were also seen in the reticular formation lateral to the MPTA and in the paramedian raphe medially (Jones and Yang, 1985;Newman, 1985;Goldsmith and van der Kooy, 1988;Rye et al, 1988;Sukhotinsky et al, 2005Sukhotinsky et al, , 2006Lu et al, 2006). Contralateral, but not ipsilateral, to the side of the injection, a distinctive paralemniscal cluster of retrogradely labeled neurons was consistently seen just ventrolateral to the MPTA cluster.…”

Section: Bulbospinal Neurons In the Mesopontine Tegmentummentioning

confidence: 97%

“…Anterograde tracing from the MPTA area reveals much more prominent projections to the VH than to the DH, even using the sensitive AAV-GFP method (Jones and Yang, 1985;Matsuyama et al, 1993;Jones, 1995;Sukhotinsky et al, 2005Sukhotinsky et al, , 2006, suggesting that few MPTA neurons terminate in the DH. However, retrograde tracing gave a very different picture; large numbers of DH-projecting MPTA neurons were revealed.…”

Section: Effects Of Location Of Tracer Microinjectionmentioning

confidence: 99%

“…We have identified a number of ascending and descending pathways employed by neurons of the MPTA (Sukhotinsky et al, 2005(Sukhotinsky et al, , 2006Reiner et al, 2007). Our working hypothesis is that motor suppression and antinociception induced by pentobarbital microinjection into the MPTA are due to specific descending pathways, whereas EEG changes and loss of consciousness are due to specific ascending pathways.…”

mentioning

confidence: 99%

“…In addition, many MPTA neurons send axons directly to the gray matter of the spinal cord. Direct bulbospinal projections of the MPTA end bilaterally throughout the entire length of the spinal cord (Satoh, 1979;Jones and Yang, 1985;Rye et al, 1988;Matsuyama et al, 1993Matsuyama et al, , 1999Sukhotinsky et al, 2005Sukhotinsky et al, , 2006. Terminations are most dense in the medial part of the ventral horn and in the intermediate gray (laminae 6 and 7).…”

mentioning

confidence: 99%

“…Terminations are most dense in the medial part of the ventral horn and in the intermediate gray (laminae 6 and 7). However, with the AAV-GFP method (recombinant adeno-associated virus vector expressing green fluorescent protein), direct projections to the superficial layers of the dorsal horn can also be visualized (Sukhotinsky et al, 2006).…”

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confidence: 99%

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Bulbospinal neurons implicated in mesopontine‐induced anesthesia are substantially collateralized

Reiner

Sukhotinsky

Devor

2008

J of Comparative Neurology

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Microinjection of pentobarbital or other gamma-aminobutyric acid type A receptor (GABA(A)-R) active anesthetics into a brainstem region in the rat that we have called the mesopontine tegmental anesthesia area (MPTA) induces a general anesthesia-like state that includes suppression of locomotor activity, loss of the righting reflex, atonia, antinociception, and apparent loss of consciousness. The suppression of muscle tone and of nocifensive spinal reflexes suggests a direct or indirect effect at the level of the spinal cord itself, an inference supported by anterograde tracing from the MPTA area. We have now used single and double retrograde tracing to characterize this bulbospinal pathway further. The MPTA contains the majority of all bulbospinal neurons present at mesopontine levels (65.8%). Many of these neurons, although not all, appear to have a highly collateralized projection pattern within the spinal cord. About 40% of the MPTA neurons that project to the lumbar spinal cord also have collaterals at cervical levels, and about 60% of those with projections to the ventral horn also have projections to the dorsal horn (at cervical levels). However, the large majority projects either ipsilaterally or contralaterally. Relatively few ( approximately 13%) send collaterals to both sides of the spinal cord. The pattern of connectivity revealed appears to be consistent with a system designed primarily to modulate motor and sensory functions globally, over the entire neuraxis, rather than regionally or segmentally.

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Section: Bulbospinal Neurons In the Mesopontine Tegmentummentioning

confidence: 97%

Section: Effects Of Location Of Tracer Microinjectionmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Bulbospinal neurons implicated in mesopontine‐induced anesthesia are substantially collateralized

Reiner

Sukhotinsky

Devor

2008

J of Comparative Neurology

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Motor organization of positive and negative emotional vocalization in the cat midbrain periaqueductal gray

Subramanian

Arun

Silburn

et al. 2015

J of Comparative Neurology

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Neurochemical microstimulation in different parts of the midbrain periaqueductal gray (PAG) in the cat generates four different types of vocalization, mews, howls, cries, and hisses. Mews signify positive vocal expression, whereas howls, hisses, and cries signify negative vocal communications. Mews were generated in the lateral column of the intermediate PAG and howls and hisses in the ventrolateral column of the intermediate PAG. Cries were generated in two regions, the lateral column of the rostral PAG and the ventrolateral column of the caudal PAG. To define the specific motor patterns belonging to mews, howls, and cries, the following muscles were recorded during these vocalizations: larynx (cricothyroid, thyroarytenoid, and posterior cricoarytenoid), tongue (genioglossus), jaw (digastric), and respiration (diaphragm, internal intercostal, external abdominal oblique, and internal abdominal oblique) muscles. Furthermore, the frequency, intensity, activation cascades, and turns and amplitude analyses of the electromyograms (EMGs) during these vocalizations were analyzed. The results show that each type of vocalization consists of a specific, circumscribed motor coordination. The nucleus retroambiguus (NRA) in the caudal medulla serves as the final premotor interneuronal output system for vocalization. NRA neurochemical microstimulation also generated vocalizations (guttural sounds). Analysis of the EMGs demonstrated that these vocalizations consist of only small parts of the emotional voalizations generated by neurochemical stimulation in the PAG. These results demonstrate that motor organization of positive and negative emotional vocal expressions are segregated in the PAG and that the PAG uses the NRA as a tool to gain access to the motoneurons generating vocalization.

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Anesthesia in mice activates discrete populations of neurons throughout the brain

Yatziv

Yudco

Vaso

et al. 2021

J of Neuroscience Research

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The brain undergoes rapid, dramatic, and reversible transitioning between states of wakefulness and unconsciousness during natural sleep and in pathological conditions such as hypoxia, hypotension, and concussion. Transitioning can also be induced pharmacologically using general anesthetic agents. The effect is selective. Mobility, sensory perception, memory formation, and awareness are lost while numerous housekeeping functions persist. How is selective transitioning accomplished? Classically a handful of brainstem and diencephalic "arousal nuclei" have been implicated in driving brain-state transitions on the grounds that their net activity systematically varies with brain state. Here we used transgenic targeted recombination in active populations mice to label neurons active during wakefulness with one reporter and neurons active during pentobarbital-induced general anesthesia with a second, contrasting reporter. We found 'wake-on' and 'anesthesia-on' neurons in widely distributed regions-of-interest, but rarely encountered neurons labeled with both reporters. Nearly all labeled neurons were either wake-on or anesthesia-on. Thus, anesthesia-on neurons are not unique to the few nuclei discovered to date whose activity appears to increase during anesthesia. Rather neuronal populations selectively active during anesthesia are located throughout the brain where they likely play a causative role in transitioning between wakefulness and anesthesia. The widespread neuronal suppression reported in prior comparisons of the awake and anesthetized brain in animal models and noninvasive imaging in humans reflects only net differences. It misses the ubiquitous presence of neurons whose activity increases during anesthesia. The balance in recruitment of anesthesia-on versus wake-on neuronal populations throughout the brain may be a key driver of regional and global vigilance states.

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Projections from the mesopontine tegmental anesthesia area to regions involved in pain modulation

Cited by 26 publications

References 95 publications

Bulbospinal neurons implicated in mesopontine‐induced anesthesia are substantially collateralized

Bulbospinal neurons implicated in mesopontine‐induced anesthesia are substantially collateralized

Motor organization of positive and negative emotional vocalization in the cat midbrain periaqueductal gray

Anesthesia in mice activates discrete populations of neurons throughout the brain

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