Sex Differences in the Hypothalamic Oxytocin Pathway to Locus Coeruleus and Augmented Attention with Chemogenetic Activation of Hypothalamic Oxytocin Neurons

Wang, Xin; Escobar, José Pablo; Mendelowitz, David

doi:10.3390/ijms22168510

Cited by 19 publications

(15 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Indeed, OT receptors are expressed in the LC and DR 30 . Using optogenetic technique, it has been shown that OT is released into the LC from hypothalamic PVN OT fibers, activating noradrenergic neurons by co-release of OT and glutamate 31 . Noradrenergic neurons in the LC and serotonergic neurons in the DR are important transitional nuclei for the descending pain inhibitory system 32,33 .…”

Section: Discussionmentioning

confidence: 99%

Endogenous oxytocin exerts anti-nociceptive and anti-inflammatory effects in rats

et al. 2022

View full text Add to dashboard Cite

Oxytocin is involved in pain transmission, although the detailed mechanism is not fully understood. Here, we generate a transgenic rat line that expresses human muscarinic acetylcholine receptors (hM3Dq) and mCherry in oxytocin neurons. We report that clozapine-N-oxide (CNO) treatment of our oxytocin-hM3Dq-mCherry rats exclusively activates oxytocin neurons within the supraoptic and paraventricular nuclei, leading to activation of neurons in the locus coeruleus (LC) and dorsal raphe nucleus (DR), and differential gene expression in GABA-ergic neurons in the L5 spinal dorsal horn. Hyperalgesia, which is robustly exacerbated in experimental pain models, is significantly attenuated after CNO injection. The analgesic effects of CNO are ablated by co-treatment with oxytocin receptor antagonist. Endogenous oxytocin also exerts anti-inflammatory effects via activation of the hypothalamus-pituitary-adrenal axis. Moreover, inhibition of mast cell degranulation is found to be involved in the response. Taken together, our results suggest that oxytocin may exert anti-nociceptive and anti-inflammatory effects via both neuronal and humoral pathways.

show abstract

Section: Discussionmentioning

confidence: 99%

Endogenous oxytocin exerts anti-nociceptive and anti-inflammatory effects in rats

et al. 2022

View full text Add to dashboard Cite

show abstract

“…Disturbing OT neuronal activity in the SON can activate the amygdala in rats ( Liu et al, 2017 ), a brain region facilitating social anxiety and fear in humans ( Meixner et al, 2019 ). Optogenetic excitation of PVN OT fibers excites noradrenergic neurons in the locus coeruleus and augments attention to novel objects by co-release of OT and glutamate in male rats ( Wang et al, 2021b ). Fear-related behaviors are rigidly controlled by the medial prefrontal cortex (mPFC) while OT-mediated decrease in neuronal activity in the mPFC could facilitate social buffering in rats ( Jung et al, 2021 ).…”

Section: Higher Brain Functionsmentioning

confidence: 99%

“…(1) (Cuneo et al, 2021;Jahangard et al, 2020;Meixner et al, 2019); (2) (Jung et al, 2021;Liu et al, 2021a;Maier et al, 2019;Wang et al, 2021b); (3) (Runyan et al, 2021;Sabe et al, 2021; (4) (John & Jaeggi, 2021;Shishido et al, 2021;Yoshihara et al, 2018;Yuan et al, 2019); (5) (Reichova et al, 2021;Tyzio et al, 2014); (6) (Francesconi et al, 2021;Huang et al, 2021;Jimenez et al, 2015;Li et al, 2020; (7) (Feifel et al, 2012;Guastella et al, 2008;Latt et al, 2018;Plasencia et al, 2019;Tse et al, 2018); (8) (Bertoni et al, 2021;Hu et al, 2015;Larrazolo-Lopez et al, 2008); (9) (Kreutzmann & Fendt, 2021;Takahashi et al, 2020 (10) (Fisher et al, 2021;La Fratta et al, 2021;Torres et al, 2022;Warrener et al, 2021); (11) (Borroto-Escuela et al, 2021;Matsushita et al, 2019;Xie et al, 2022;Yoshida et al, 2009); (12) …”

Section: Pro-social Behaviormentioning

confidence: 99%

Neural Functions of Hypothalamic Oxytocin and its Regulation

Wang

Liu

et al. 2022

ASN Neuro

View full text Add to dashboard Cite

Oxytocin (OT), a nonapeptide, has a variety of functions. Despite extensive studies on OT over past decades, our understanding of its neural functions and their regulation remains incomplete. OT is mainly produced in OT neurons in the supraoptic nucleus (SON), paraventricular nucleus (PVN) and accessory nuclei between the SON and PVN. OT exerts neuromodulatory effects in the brain and spinal cord. While magnocellular OT neurons in the SON and PVN mainly innervate the pituitary and forebrain regions, and parvocellular OT neurons in the PVN innervate brainstem and spinal cord, the two sets of OT neurons have close interactions histologically and functionally. OT expression occurs at early life to promote mental and physical development, while its subsequent decrease in expression in later life stage accompanies aging and diseases. Adaptive changes in this OT system, however, take place under different conditions and upon the maturation of OT release machinery. OT can modulate social recognition and behaviors, learning and memory, emotion, reward, and other higher brain functions. OT also regulates eating and drinking, sleep and wakefulness, nociception and analgesia, sexual behavior, parturition, lactation and other instinctive behaviors. OT regulates the autonomic nervous system, and somatic and specialized senses. Notably, OT can have different modulatory effects on the same function under different conditions. Such divergence may derive from different neural connections, OT receptor gene dimorphism and methylation, and complex interactions with other hormones. In this review, brain functions of OT and their underlying neural mechanisms as well as the perspectives of their clinical usage are presented.

show abstract

“…Oxt is known to increase LC adrenergic receptor responsiveness and thus enhance salience of received cues in rats ( Petersson et al, 1998 ). Optogenetic activation of PVH-Oxt neurons in rat brain resulted in downstream activation of LC-noradrenaline followed by an enhanced attention to novel objects suggesting that Oxt directly regulates attention by modulating LC responses ( Wang et al, 2021 ). The LC also receives monosynaptic inputs from another attention relevant area called the pedunculopontine nucleus (PPN), an area with abundant Oxt neuronal fibers.…”

Section: Oxytocin Associated Circuitry In Internal State Controlmentioning

confidence: 99%

Missing pieces in decoding the brain oxytocin puzzle: Functional insights from mouse brain wiring diagrams

Manjila

Betty²,

Kim³

2022

Front. Neurosci.

View full text Add to dashboard Cite

The hypothalamic neuropeptide, oxytocin (Oxt), has been the focus of research for decades due to its effects on body physiology, neural circuits, and various behaviors. Oxt elicits a multitude of actions mainly through its receptor, the Oxt receptor (OxtR). Despite past research to understand the central projections of Oxt neurons and OxtR- coupled signaling pathways in different brain areas, it remains unclear how this nonapeptide exhibits such pleiotropic effects while integrating external and internal information. Most reviews in the field either focus on neuroanatomy of the Oxt-OxtR system, or on the functional effects of Oxt in specific brain areas. Here, we provide a review by integrating brain wide connectivity of Oxt neurons and their downstream circuits with OxtR expression in mice. We categorize Oxt connected brain regions into three functional modules that regulate the internal state, somatic visceral, and cognitive response. Each module contains three neural circuits that process distinct behavioral effects. Broad innervations on functional circuits (e.g., basal ganglia for motor behavior) enable Oxt signaling to exert coordinated modulation in functionally inter-connected circuits. Moreover, Oxt acts as a neuromodulator of neuromodulations to broadly control the overall state of the brain. Lastly, we discuss the mismatch between Oxt projections and OxtR expression across various regions of the mouse brain. In summary, this review brings forth functional circuit-based analysis of Oxt connectivity across the whole brain in light of Oxt release and OxtR expression and provides a perspective guide to future studies.

show abstract

Sex Differences in the Hypothalamic Oxytocin Pathway to Locus Coeruleus and Augmented Attention with Chemogenetic Activation of Hypothalamic Oxytocin Neurons

Cited by 19 publications

References 20 publications

Endogenous oxytocin exerts anti-nociceptive and anti-inflammatory effects in rats

Endogenous oxytocin exerts anti-nociceptive and anti-inflammatory effects in rats

Neural Functions of Hypothalamic Oxytocin and its Regulation

Missing pieces in decoding the brain oxytocin puzzle: Functional insights from mouse brain wiring diagrams

Contact Info

Product

Resources

About