The antinociceptive effect of anterior pretectal nucleus stimulation is mediated by distinct neurotransmitter mechanisms in descending pain pathways

Genaro, Karina; Fabris, Débora Cristina Niero; Prado, Wiliam A.

doi:10.1016/j.brainresbull.2019.01.003

Cited by 8 publications

(7 citation statements)

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“…It receives inputs from a large array of somatosensory associated pathways, including nociception. Activation of the APT results in antinociception, that is, suppression of reflexes induced by pain, such as the tail flick or jaw‐opening reflexes, through its outputs to the DpMe, PPTG, and LPGi (Chiang, Dostrovsky, & Sessle, 1991; Genaro, Fabris, & Prado, 2019; Genaro & Prado, 2016). In Brn3c Cre/WT ; Rosa26 tdTomato/WT mice, both APT and DpMe contain tdTomato + cell bodies, while DpMe targets, such as the pontine and gigantocellular reticular regions contain tdTomato + fibers.…”

Section: Discussionmentioning

confidence: 99%

“…APT-DpMe pathway in antinociception: The APT is part of the PTA, neighboring several nuclei associated with vision (e.g., olivary pretectal nucleus and nucleus of the optic tract), however, extends caudally deeper into the midbrain (Rees & Roberts, 1993). LPGi (Chiang, Dostrovsky, & Sessle, 1991;Genaro, Fabris, & Prado, 2019;Genaro & Prado, 2016). In Brn3c Cre/WT ; Rosa26 tdTomato/ WT mice, both APT and DpMe contain tdTomato + cell bodies, while (Masullo et al, 2019).…”

Section: Midbrain Neurons Labeled In Brn3c Cre Micementioning

confidence: 99%

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Identification of retinal ganglion cell types and brain nuclei expressing the transcription factor Brn3c/Pou4f3 using a Cre recombinase knock‐in allele

Parmhans

Fuller

Nguyen

et al. 2020

J of Comparative Neurology

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Members of the POU4F/Brn3 transcription factor family have an established role in the development of retinal ganglion cell (RGCs) types, the main transducers of visual information from the mammalian eye to the brain. Our previous work using sparse random recombination of a conditional knock-in reporter allele expressing alkaline phosphatase (AP) and intersectional genetics had identified three types of Brn3c positive (Brn3c +) RGCs. Here, we describe a novel Brn3c Cre mouse allele generated by serial Dre to Cre recombination and use it to explore the expression overlap of Brn3c with Brn3a and Brn3b and the dendritic arbor morphologies and visual stimulus response properties of Brn3c + RGC types. Furthermore, we explore brain nuclei that express Brn3c or receive input from Brn3c + neurons. Our analysis reveals a much larger number of Brn3c + RGCs and more diverse set of RGC types than previously reported. Most RGCs expressing Brn3c during development are still Brn3c positive in the adult, and all express Brn3a while only about half express Brn3b. Genetic Brn3c-Brn3b intersection reveals an area of increased RGC density, extending from dorsotemporal to ventrolateral across the retina and overlapping with the mouse binocular field of view. In addition, we report a Brn3c + RGC projection to the thalamic reticular nucleus, a visual nucleus that was not previously shown to receive retinal input. Furthermore, Brn3c + neurons highlight a previously unknown subdivision of the deep mesencephalic nucleus. Thus, our newly generated allele provides novel biological insights into RGC type classification, brain connectivity, and cytoarchitectonic.

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Section: Discussionmentioning

confidence: 99%

Section: Midbrain Neurons Labeled In Brn3c Cre Micementioning

confidence: 99%

Identification of retinal ganglion cell types and brain nuclei expressing the transcription factor Brn3c/Pou4f3 using a Cre recombinase knock‐in allele

Parmhans

Fuller

Nguyen

et al. 2020

J of Comparative Neurology

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“…We verified that naloxone, but not methysergide or AP‐7 (an N‐methyl‐D‐aspartate receptor antagonist), intra‐LPGi injection prevents APtN stimulation‐evoked antinociception in rats with neurotoxically lesioned PPTgs. In addition, we observed that mecamylamine (a cholinergic nicotinic receptor antagonist), methysergide, or AP‐7 administration into the PPTg of rats with neurotoxically lesioned contralateral LPGi blocks APtN stimulation‐evoked antinociception (Genaro et al., 2019). These results confirmed that two pain inhibitory pathways are activated from the APtN and showed that endogenous opioid signaling in the ipsilateral LPGi and cholinergic nicotinic, serotonergic, and glutamate mechanisms in the contralateral PPTg appear to be necessary for APtN stimulation‐evoked antinociception (Figure 4, right).…”

Section: Mediation Involved In Descending Pathways From the Aptnmentioning

confidence: 99%

“…A prodigious amount of research suggests that APtN stimulation, either electrically or by microinjection of different neurochemicals, produces long‐lasting antinociceptive effects in different pain models in rats (Chiang et al., 1989; Genaro et al., 2019; Genaro & Prado, 2016; Neto et al., 1999; Porro et al., 1999; Prado, 1989; Prado & Faganello, 2000; Prado & Roberts, 1985; Rees et al., 1987; Rhodes & Liebeskind, 1978; Roberts & Rees, 1986; Rosa et al., 1998; Rosa & Prado, 1997; Rossaneis & Prado, 2015; Terenzi et al., 1995; Villarreal et al., 2003, 2004b; Villarreal & Prado, 2007; Wang et al., 1992; Wilson et al., 1991). Injecting glutamate or D,L‐homocysteic acid into the APtN also inhibits the tail‐flick reflex (Prado, 1989; Rees, Roberts, et al., 1987), thus indicating that changes in the nociception response result from activation of cell bodies but not from fibers passing through the APtN.…”

Section: The Aptn Mediates Top‐down Control Of Painmentioning

confidence: 99%

The role of the anterior pretectal nucleus in pain modulation: A comprehensive review

Genaro

Prado

2021

Eur J of Neuroscience

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A nociceptive stimulus initiates a cascade of events. An effective way to understand the physiology of pain sensation is to follow the nociceptive signaling pathway from the periphery to the central nervous system (CNS), with a focus on the neuroanatomical, neurochemical, and molecular mechanisms that integrate and modulate nociceptive signals.The term nociception is used to describe the signal following an injury that will be modulated at multiple steps within

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“…Activation of the APT results in antinociception, i.e. suppression of reflexes induced by pain, such as the tail flick or jaw-opening reflexes, through its outputs to the DpMe, PPTG and LPGi (Chiang, Dostrovsky, & Sessle, 1991;Genaro, Fabris, & Prado, 2019;Genaro & Prado, 2016). In Brn3c Cre/WT ; Rosa26 tdTomato/WT mice, both APT and DpMe contain tdTomato + cell bodies, while DpMe targets, such as the pontine and gigantocellular reticular regions contain tdTomato + fibers.…”

Section: Midbrain Neurons Labelled In Brn3c Cre Micementioning

confidence: 99%

Identification of Retinal Ganglion Cell Types and Brain Nuclei expressing the transcription factor Brn3c/Pou4f3 using a Cre recombinase knock-in allele

Parmhans

Fuller

Nguyen

et al. 2020

Preprint

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Members of the POU4F/Brn3 transcription factor family have an established role in the development of retinal ganglion cell types (RGCs), the projection sensory neuron conveying visual information from the mammalian eye to the brain. Our previous work using sparse random recombination of a conditional knock-in reporter allele expressing Alkaline Phosphatase (AP) and intersectional genetics had identified three types of Pou4f3/Brn3c positive (Brn3c + ) RGCs. Here, we describe a novel Brn3c Cre mouse allele generated by serial Dre to Cre recombination. We use this allele to explore the expression overlap of Brn3c with Brn3a and Brn3b and the dendritic arbor morphologies and visual stimulus properties of Brn3c + RGC types. Furthermore, we explore Brn3c-expressing brain nuclei. Our analysis reveals a much larger number of Brn3c + RGCs and more diverse set of RGC types than previously reported. The majority of RGCs having expressed Brn3c during development are still Brn3c positive in the adult, and all of them express Brn3a while only about half express Brn3b. Intersection of Brn3b and Brn3c expression highlights an area of increased RGC density, similar to an area centralis, corresponding to part of the binocular field of view of the mouse. Brn3c + neurons and projections are present in multiple brain nuclei. Brn3c + RGC projections can be detected in the Lateral Geniculate Nucleus (LGN), Pretectal Area (PTA) and Superior Colliculus (SC) but also in the thalamic reticular nucleus (TRN), a visual circuit station that was not previously described to receive retinal input. Most Brn3c + neurons of the brain are confined to the pretectum and the dorsal midbrain. Amongst theses we identify a previously unknown Brn3c + subdivision of the deep mesencephalic nucleus (DpMe). Thus, our newly generated allele provides novel biological insights into RGC type classification, brain connectivity and midbrain cytoarchitectonic, and opens the avenue for specific characterization and manipulation of these structures.Retinal Ganglion Cells (RGCs) are projection sensory neurons that convey multiple aspects of visual information from the eye to retinorecipient areas of the brain (Ramón y Cajal, 1972). Work in many species has documented the abundant diversity among RGC types, by characterizing distinctions in dendritic arbors, responses to visual stimuli, projections to a variety of brain nuclei and circuit

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The antinociceptive effect of anterior pretectal nucleus stimulation is mediated by distinct neurotransmitter mechanisms in descending pain pathways

Cited by 8 publications

References 58 publications

Identification of retinal ganglion cell types and brain nuclei expressing the transcription factor Brn3c/Pou4f3 using a Cre recombinase knock‐in allele

Identification of retinal ganglion cell types and brain nuclei expressing the transcription factor Brn3c/Pou4f3 using a Cre recombinase knock‐in allele

The role of the anterior pretectal nucleus in pain modulation: A comprehensive review

Identification of Retinal Ganglion Cell Types and Brain Nuclei expressing the transcription factor Brn3c/Pou4f3 using a Cre recombinase knock-in allele

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