Oxytocin promotes prefrontal population activity via the PVN-PFC pathway to regulate pain

Liu, Yaling; Li, Anna; Bair-Marshall, Chloe J.; Xu, Helen; Jee, Hyun Jung; Zhu, Elaine; Sun, Mengqi; Zhang, Qiaosheng; Lefèvre, Arthur; Chen, Zhe; Grinevich, Valery; Froemke, Robert C.; Wang, Jing

doi:10.1016/j.neuron.2023.03.014

Cited by 23 publications

(11 citation statements)

References 86 publications

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“…5). These results are consistent with recent work showing that OT and OTR knockout rat pups had impaired preference for homecage bedding over unfamiliar bedding, but distinct in that knockout rats were not defective in USV emission during MS (Liu et al, 2023b). Although the different models (i.e., pharmacological vs. transgenic) and contexts (i.e., reunion vs. separation USVs) are difficult to compare, the inter-species variability in OTR developmental expression might contribute to the speciesand context-specific behavioral repertoire and explain the different responses to OTR perturbations (Grinevich et al, 2014;Jurek and Neumann, 2018).…”

Section: Discussionsupporting

confidence: 93%

“…Pioneering work by James Winslow and Thomas Insel has laid the foundation for understanding OT’s role in MS-induced USVs in early life (Winslow et al, 2000; Winslow and Insel, 2002; Insel and Winslow, 1991). Recently, OT was shown to play a conserved role in affiliative behavior toward the dam in both rodents and monkeys, although not in USV emission during MS (Liu et al, 2023b). Further research showed that OT signaling drives the changes in social behavior following one week of post-weaning social isolation in mice (Musardo et al, 2022).…”

Section: Resultsmentioning

confidence: 99%

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Oxytocin signaling regulates maternally-directed behavior during early life

Zelmanoff,

Kaufman,

Dine

et al. 2024

Preprint

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Oxytocin is essential in shaping social behavior across the lifespan. While the role of oxytocin signaling in parental care has been widely investigated, little is known about its function in social behavior during early life. This is partly due to the lack of precise technologies for studying the developing brain. Here, we studied the role of oxytocin in pup social behavior under acute separation from and reunion with the mother. We show that the activity of oxytocin neurons was increased by acute maternal separation and returned to baseline after reunion. Behaviorally, maternally separated pups emitted more ultrasonic vocalizations upon reunion, which were further modulated by nipple attachment behavior. These effects were attenuated by blocking the oxytocin receptor during maternal separation. To investigate the role of oxytocin neurons with higher precision, we established a method for transcranial optogenetic silencing of neuronal activity in untethered and freely behaving pups. Using this approach, we found that silencing of oxytocin neurons during maternal separation disrupted vocal behavior during separation and reunion in a sex-specific manner. Our findings reveal an important role of oxytocin in context-dependent vocal communication in pups, offering new insights into the mechanisms of social behavior during early life.

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Section: Discussionsupporting

confidence: 93%

Section: Resultsmentioning

confidence: 99%

Oxytocin signaling regulates maternally-directed behavior during early life

Zelmanoff,

Kaufman,

Dine

et al. 2024

Preprint

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show abstract

“…We then attached a single-photon miniscope to the GRIN lens to track Ca 2+ activity within CAMKII-expressing neurons, which are mostly excitatory neurons. 37 , 38 For each recording session, we measured Ca 2+ activity for 5 min with no external stimuli for a baseline measurement ( Figure 3(c) ). We then measured Ca 2+ activity after the delivery of a non-noxious von Frey (vF) mechanical stimulus versus the delivery of the PP stimulus.…”

Section: Resultsmentioning

confidence: 99%

AMPAkines have site-specific analgesic effects in the cortex

Zhu,

Mathew,

Jee

et al. 2024

Mol Pain

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Different brain areas have distinct roles in the processing and regulation of pain and thus may form specific pharmacological targets. Prior research has shown that AMPAkines, a class of drugs that increase glutamate signaling, can enhance descending inhibition from the prefrontal cortex (PFC) and nucleus accumbens. On the other hand, activation of neurons in the anterior cingulate cortex (ACC) is known to produce the aversive component of pain. The impact of AMPAkines on ACC, however, is not known. We found that direct delivery of CX516, a well-known AMPAkine, into the ACC had no effect on the aversive response to pain in rats. Furthermore, AMPAkines did not modulate the nociceptive response of ACC neurons. In contrast, AMPAkine delivery into the prelimbic region of the prefrontal cortex (PL) reduced pain aversion. These results indicate that the analgesic effects of AMPAkines in the cortex are likely mediated by the PFC but not the ACC.

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“…We believe that these seemingly contradictory results further highlight the important role of PVN in visceral pain. The PVN is a heterogeneous nucleus containing various types of neurons ( 16 ), which determines its complex functionality. Arginine vasopressin (AVP)-positive neurons in the PVN project to the solitary tract nucleus; therefore, activating AVP-positive neurons can protect intestinal mucosa through the vagus nerve and relieve visceral pain ( 14 ).…”

Section: Discussionmentioning

confidence: 99%

Inhibition of GABAergic neurons in the paraventricular nucleus of the hypothalamus precipitates visceral pain induced by pancreatic cancer in mice

Ji,

Li,

Cao

et al. 2024

J Gastrointest Oncol

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Background For patients with pancreatic cancer, visceral pain is a debilitating symptom that significantly compromises their quality of life. Unfortunately, the lack of effective treatment options can be attributed to our limited understanding of the neural circuitry underlying this phenomenon. The primary objective of this study is to elucidate the fundamental mechanisms governing visceral pain induced by pancreatic cancer in murine models. Methods A mouse model of pancreatic cancer visceral pain was established in C57BL/6N mice through the intrapancreatic injection of mPA KPC -luc cells. Abdominal mechanical hyperalgesia and hunch score were employed to evaluate visceral pain, whereas the in vitro electrophysiological patch-clamp technique was utilized to record the electrophysiological activity of GABAergic neurons. Specific neuron ablation and chemogenetics methods were employed to investigate the involvement of GABAergic neurons in pancreatic cancer-induced visceral pain. Results In vitro electrophysiological results showed that the firing frequency of GABAergic neurons in the paraventricular nucleus of the hypothalamus (PVN) was decreased. Specific destruction of GABAergic neurons in the PVN exacerbated visceral pain induced by pancreatic cancer. Chemogenetics activation of GABAergic neurons in the PVN alleviated visceral pain induced by pancreatic cancer. Conclusions GABAergic neurons located in PVN play a crucial role in precipitating visceral pain induced by pancreatic cancer in mice, thereby offering novel insights for identifying effective targets to treat pancreatic cancer-related visceral pain.

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Oxytocin promotes prefrontal population activity via the PVN-PFC pathway to regulate pain

Cited by 23 publications

References 86 publications

Oxytocin signaling regulates maternally-directed behavior during early life

Oxytocin signaling regulates maternally-directed behavior during early life

AMPAkines have site-specific analgesic effects in the cortex

Inhibition of GABAergic neurons in the paraventricular nucleus of the hypothalamus precipitates visceral pain induced by pancreatic cancer in mice

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