scholarly journals Corticotropin-Releasing Factor Neurons in the Bed Nucleus of the Stria Terminalis Differentially Influence Pain Processing and Modulation in Male and Female Mice

2020 ◽  
Author(s):  
Waylin Yu ◽  
Christina M. Stanhope ◽  
Natalia del R. Rivera Sanchez ◽  
Garrett A. Moseley ◽  
Thomas L. Kash
Keyword(s):  
Pain Modulation ◽  
Corticotropin Releasing Factor ◽  
Stria Terminalis ◽  
Noxious Heat ◽  
Specific Expression ◽  
Male And Female ◽  
Bed Nucleus ◽  
Female Mice ◽  
Pain Knowledge

AbstractThe bed nucleus of the stria terminalis (BNST) plays an emerging yet understudied role in pain. Corticotropin-releasing factor (CRF) is an important source of pain modulation in the BNST, with local pharmacological inhibition of CRF receptors conditionally impacting the sensory and affective-motivational components of pain. Knowledge on how pain dynamically engages CRF neurons in the BNST and is influenced by intra-BNST production of CRF, however, remains unknown. In the present study, we utilized in vivo calcium imaging to show robust and synchronized recruitment of BNSTCRF+ neurons during acute exposure to noxious heat. Distinct patterns of recruitment were observed by sex, as the magnitude and timing of heat responsive activity in BNSTCRF+ neurons differed for male and female mice. We then established the necessity of CRF for intact pain behaviors by genetically deleting Crf in the BNST, which reduced thermal and mechanical nociceptive sensitivity for both sexes, and increased paw attending in female mice, suggesting a divergent role for CRF with respect to active coping responses to pain. Together, these findings demonstrate that CRF in the BNST contributes to multiple facets of the pain experience and may play a key role in the sex-specific expression of pain-related behaviors.

scholarly journals Corticotropin-releasing factor neurons in the bed nucleus of the stria terminalis exhibit sex-specific pain encoding in mice

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Waylin Yu ◽  
Christina M. Caira ◽  
Natalia del R. Rivera Sanchez ◽  
Garrett A. Moseley ◽  
Thomas L. Kash
Keyword(s):  
Corticotropin Releasing Factor ◽  
Stria Terminalis ◽  
Noxious Heat ◽  
Specific Expression ◽  
Pain Experience ◽  
Bed Nucleus ◽  
Cell Type Specific ◽  
In Vivo Calcium Imaging ◽  
Pain Regulation

AbstractThe bed nucleus of the stria terminalis (BNST) plays an emerging role in pain regulation. Pharmacological studies have found that inhibiting corticotropin-releasing factor (CRF) signaling in the BNST can selectively mitigate the sensory and affective-motivational components of pain. However, mechanistic insight on the source of CRF that drives BNST responses to these harmful experiences remains unknown. In the present study, we used a series of genetic approaches to show that CRF in the BNST is engaged in the processing and modulation of pain. We conducted cell-type specific in vivo calcium imaging in CRF-Cre mice and found robust and synchronized recruitment of BNSTCRF neurons during acute exposures to noxious heat. Distinct patterns of recruitment were observed by sex, as the magnitude and timing of heat responsive activity in BNSTCRF neurons differed for male and female mice. We then used a viral approach in Floxed-CRF mice to selectively reduce CRF expression in the BNST and found it decreased nociceptive sensitivity for both sexes and increased paw attending for females. Together, these findings reveal that CRF in the BNST influences multiple facets of the pain experience to impact the sex-specific expression of pain-related behaviors.

scholarly journals Male and female mice demonstrate divergent cellular responses in the bed nucleus of stria terminalis (BNST) following morphine withdrawal

2018 ◽  
Author(s):  
Brennon R. Luster ◽  
Elizabeth S. Cogan ◽  
Karl T. Schmidt ◽  
Dipanwita Pati ◽  
Melanie M. Pina ◽  
...  
Keyword(s):  
Opioid Analgesics ◽  
Cellular Responses ◽  
The United States ◽  
Morphine Withdrawal ◽  
Stria Terminalis ◽  
Male Mice ◽  
Male And Female ◽  
Bed Nucleus ◽  
Precipitated Withdrawal ◽  
Female Mice

AbstractThe United States is experiencing an opioid epidemic of significant proportions, imposing enormous fiscal and societal costs. While prescription opioid analgesics are essential for treating pain, the cessation of these drugs can induce a withdrawal syndrome, and thus opioid use often persists to alleviate or avoid these symptoms. Therefore, it is essential to understand the neurobiology underlying this critical window of withdrawal from opioid analgesics to prevent continued usage. To model this, we administered a low dose of morphine, and precipitated withdrawal with naloxone to investigate the behavioral and cellular responses in C57BL/6J male and female mice. Following 3 days of administration, both male and female mice sensitized to the repeated bouts of withdrawal, as evidenced by their composite global withdrawal score. Female mice exhibited increased withdrawal symptoms on some individual measures, but did not show characteristic weight loss observed in male mice. Because of its role in mediating withdrawal-associated behaviors, we examined neuronal excitability and inhibitory synaptic transmission in the bed nucleus of the stria terminalis (BNST) 24 hours following the final precipitated withdrawal. In male mice, morphine withdrawal increased spontaneous GABAergic signaling compared to controls. In contrast, morphine withdrawal decreased spontaneous GABAergic signaling, and increased BNST projection neuron excitability in female mice. Intriguingly, these opposing GABAergic effects were dependent on within slice excitability. Our findings suggest that male and female mice manifest divergent cellular responses in the BNST following morphine withdrawal, and alterations in BNST inhibitory signaling may be a significant factor contributing to the expression of behaviors following opioid withdrawal.

scholarly journals Inhibitory transmission in the bed nucleus of the stria terminalis in male and female mice following morphine withdrawal

2019 ◽  
Vol 25 (3) ◽  
Author(s):  
Brennon R. Luster ◽  
Elizabeth S. Cogan ◽  
Karl T. Schmidt ◽  
Dipanwita Pati ◽  
Melanie M. Pina ◽  
...  
Keyword(s):  
Morphine Withdrawal ◽  
Stria Terminalis ◽  
Male And Female ◽  
Bed Nucleus ◽  
Inhibitory Transmission ◽  
Female Mice

scholarly journals Corrigendum: In vivo Hippocampal Serotonin Dynamics in Male and Female Mice: Determining Effects of Acute Escitalopram Using Fast Scan Cyclic Voltammetry

2019 ◽  
Vol 13 ◽  
Author(s):  
Rachel A. Saylor ◽  
Melinda Hersey ◽  
Alyssa West ◽  
Anna Marie Buchanan ◽  
Shane N. Berger ◽  
...  
Keyword(s):  
Cyclic Voltammetry ◽  
Fast Scan Cyclic Voltammetry ◽  
Male And Female ◽  
Female Mice

scholarly journals Corticotropin-releasing factor infusion in the bed nucleus of the stria terminalis of lactating mice alters maternal care and induces behavioural phenotypes in offspring

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Kerstin Camile Creutzberg ◽  
Érika Kestering-Ferreira ◽  
Thiago Wendt Viola ◽  
Luis Eduardo Wearick-Silva ◽  
Rodrigo Orso ◽  
...  
Keyword(s):  
Locomotor Activity ◽  
Maternal Care ◽  
Corticotropin Releasing Factor ◽  
Maternal Behaviour ◽  
Stria Terminalis ◽  
Bed Nucleus ◽  
Plus Maze ◽  
Maternal Brain ◽  
Nesting Material ◽  
Peripartum Period

AbstractThe peripartum period is accompanied by numerous physiological and behavioural adaptations organised by the maternal brain. These changes are essential for adequate expression of maternal behaviour, thereby ensuring proper development of the offspring. The corticotropin-releasing factor (CRF) plays a key role in a variety of behaviours accompanying stress, anxiety, and depression. There is also evidence that CRF contributes to maladaptations during the peripartum period. We investigated the effects of CRF in the bed nucleus of the stria terminalis (BNST) of lactating mice during maternal care and analysed locomotor activity and anxiety-like behaviour in the offspring. The BNST has been implicated in anxiety behaviour and regulation of the stress response. The effects of intra-BNST CRF administration were compared with those induced by the limited bedding (LB) procedure, a model that produces altered maternal behaviour. BALB/cJ dams were exposed to five infusions of CRF or saline into the BNST in the first weeks after birth while the LB dams were exposed to limited nesting material from postnatal days (P) 2–9. Maternal behaviour was recorded in intercalated days, from P1-9. Offspring anxiety-like behaviour was assessed during adulthood using the open-field, elevated plus-maze, and light/dark tests. Both intra-BNST CRF and LB exposure produced altered maternal care, represented by decreased arched-back nursing and increased frequency of exits from the nest. These changes in maternal care resulted in robust sex-based differences in the offspring’s behavioural responses during adulthood. Females raised by CRF-infused dams exhibited increased anxiety-like behaviour, whereas males presented a significant decrease in anxiety. On the other hand, both males and females raised by dams exposed to LB showed higher locomotor activity. Our study demonstrates that maternal care is impaired by intra-BNST CRF administrations, and these maladaptations are similar to exposure to adverse early environments. These procedures, however, produce distinct phenotypes in mice during young adulthood and suggest sex-based differences in the susceptibility to poor maternal care.

Sign in / Sign up

Export Citation Format

Share Document