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PloS One 2023The ability to detect, appraise, and respond to another's emotional state is essential to social affective behavior. This is mediated by a network of brain regions...
The ability to detect, appraise, and respond to another's emotional state is essential to social affective behavior. This is mediated by a network of brain regions responsible for integrating external cues with internal states to orchestrate situationally appropriate behavioral responses. The basolateral amygdala (BLA) and the insular cortex are reciprocally connected regions involved in social cognition and prior work in male rats revealed their contributions to social affective behavior. We investigated the functional role of these regions in female rats in a social affective preference (SAP) test in which experimental rats approach stressed juvenile but avoid stressed adult conspecifics. In separate experiments, the BLA or the insula were inhibited by local infusion of muscimol (100ng/side in 0.5μL saline) or vehicle prior to SAP tests. In both regions, muscimol interfered with preference for the stressed juvenile and naive adult, indicating that these regions are necessary for appropriate social affective behavior. In male rats, SAP behavior requires insular oxytocin but there are noteworthy sex differences in the oxytocin receptor distribution in rats. Oxytocin (500nM) administered to the insula did not alter social behavior but oxytocin infusions to the BLA increased social interaction. In sum, female rats appear to use the same BLA and insula regions for social affective behavior but sex differences exist in contribution of oxytocin in the insula.
Topics: Rats; Female; Male; Animals; Basolateral Nuclear Complex; Oxytocin; Insular Cortex; Muscimol; Social Behavior
PubMed: 37797037
DOI: 10.1371/journal.pone.0281794 -
Molecular Neurobiology Mar 2024Norepinephrine (NE) is involved in auditory fear conditioning (AFC) in posttraumatic stress disorder (PTSD). However, it is still unclear how it acts on neurons. We...
Norepinephrine (NE) is involved in auditory fear conditioning (AFC) in posttraumatic stress disorder (PTSD). However, it is still unclear how it acts on neurons. We aimed to investigate whether the activation of the β-adrenergic receptor (β-AR) improves AFC by sensitization of the prelimbic (PL) cortex at the animal, cellular, and molecular levels. In vivo single-cell electrophysiological recording was used to characterize the changes in neurons in the PL cortex after AFC. Then, PL neurons were locally administrated by the β-AR agonist isoproterenol (ISO), the GABAaR agonist muscimol, or intervened by optogenetic method, respectively. Western blotting and immunohistochemistry were finally used to assess molecular changes. Noise and low-frequency tones induced similar AFC. The expression of β-ARs in PL cortex neurons was upregulated after fear conditioning. Microinjection of muscimol into the PL cortex blocked the conformation of AFC, whereas ISO injection facilitated AFC. Moreover, PL neurons can be distinguished into two types, with type I but not type II neurons responding to conditioned sound and being regulated by β-ARs. Our results showed that β-ARs in the PL cortex regulate conditional fear learning by activating type I PL neurons.
Topics: Animals; Prefrontal Cortex; Muscimol; Receptors, Adrenergic, beta; Signal-To-Noise Ratio; Isoproterenol; Fear
PubMed: 37787950
DOI: 10.1007/s12035-023-03667-3 -
The Korean Journal of Pain Oct 2023: Muscimol's quick onset and GABAergic properties make it a promising candidate for the treatment of pain. This systematic review and meta-analysis of preclinical...
BACKGROUND
: Muscimol's quick onset and GABAergic properties make it a promising candidate for the treatment of pain. This systematic review and meta-analysis of preclinical studies aimed at summarizing the evidence regarding the efficacy of muscimol administration in the amelioration of nerve injury-related neuropathic pain.
METHODS
: Two independent researchers performed the screening process in Medline, Embase, Scopus and Web of Science extracting data were extracted into a checklist designed according to the PRISMA guideline. A standardized mean difference (SMD [95% confidence interval]) was calculated for each. To assess the heterogeneity between studies, I and chi-square tests were utilized. In the case of heterogeneity, meta-regression and subgroup analyses were performed to identify the potential source.
RESULTS
: Twenty-two articles met the inclusion criteria. Pooled data analysis showed that the administration of muscimol during the peak effect causes a significant reduction in mechanical allodynia (SMD = 1.78 [1.45-2.11]; < 0.0001; I = 72.70%), mechanical hyperalgesia (SMD = 1.62 [1.28-1.96]; < 0.0001; I = 40.66%), and thermal hyperalgesia (SMD = 2.59 [1.79-3.39]; < 0.0001; I = 80.33%). This significant amendment of pain was observed at a declining rate from 15 minutes to at least 180 minutes post-treatment in mechanical allodynia and mechanical hyperalgesia, and up to 30 minutes in thermal hyperalgesia ( < 0 .0001).
CONCLUSIONS
: Muscimol is effective in the amelioration of mechanical allodynia, mechanical hyperalgesia, and thermal hyperalgesia, exerting its analgesic effects 15 minutes after administration for up to at least 3 hours.
PubMed: 37732408
DOI: 10.3344/kjp.23161 -
The International Journal of... Nov 2023The high individual variability in coping with stress is often attributed to genetic background differences, sustained environmental conditions, or a combination of...
BACKGROUND
The high individual variability in coping with stress is often attributed to genetic background differences, sustained environmental conditions, or a combination of both. However, the neural mechanisms underlying coping style variability are still poorly understood.
METHODS
Here we examined the impact of a single extended emotional challenge on coping style variability and the associated involvement of the hippocampus, medial prefrontal cortex (mPFC), and periaqueductal gray (PAG). Male Sprague-Dawley rats (n = 170) were trained in an extended 2-way shuttle avoidance (eTWSA) task for 7 days, and daily avoidance rates were measured. Forced swim test, elevated plus maze, or Morris water maze was tested before or after eTWSA exposure. Excitotoxic lesion of the hippocampal dentate gyrus (DG) was performed by Ibotenic infusion. Transient pharmacological blocking of DG, mPFC, or PAG was performed by muscimol or CNQX+TTX infusion.
RESULTS
Exposing rats to eTWSA was found to lead to naturally developing dichotomous, not continuous, coping styles, which we termed active avoidance (AA) or reactive escape (RE). Prior emotional responses did not predict the developing coping style. AA was associated with beneficial outcomes, including reduced behavioral despair and improved spatial learning. RE led to impaired spatial retrieval. AA was abolished by lesioning or pharmacological blocking of the DG. RE was prevented by blocking mPFC or PAG.
CONCLUSION
The results indicate that a single exposure to a significant emotional challenge can lead, in otherwise healthy individuals, to dichotomous development of an active or reactive coping style with distinctive neural correlates and subsequent behavioral significance.
Topics: Rats; Male; Animals; Rats, Sprague-Dawley; Emotions; Adaptation, Psychological; Prefrontal Cortex; Cognition; Avoidance Learning
PubMed: 37725443
DOI: 10.1093/ijnp/pyad054 -
Physiology & Behavior Nov 2023Rapid eye movement (REM) sleep plays a significant role in visuospatial learning and memory consolidation; however, its mechanism of action is unknown. Rapid eye...
Rapid eye movement (REM) sleep plays a significant role in visuospatial learning and memory consolidation; however, its mechanism of action is unknown. Rapid eye movements (REMs), a characteristic active feature of REM sleep, is a potential correlate of neural processing for visual memory consolidation. The superior colliculus (SC) plays a central role in oculomotor control and spatial localization of objects in the visual field. We proposed that local reversible inactivation of the SC during post-learning sessions might interfere with REMs and negatively impact REM sleep associated consolidation of the visuospatial learnt task. Under gaseous anesthesia, bilateral cannulae aiming SC and electrodes for recording electrophysiological signals to classify sleep-waking were implanted. Following standard protocol, all rats were subjected to Morris water maze (MWM) training for 5 consecutive days followed by probe trial. After MWM training, on all except the probe test days, the rat SC were bilaterally infused with either vehicle (control, Group 1), Lidocaine hydrochloride a local anesthetic (Lox 2%, Group 2), or muscimol (Mus, GABA agonist, Group 3) and sleep-wakefulness recorded after day 1, 4, and post-probe learning sessions. Post-learning, compared to vehicle, Mus treated group significantly decreased REMs, phasic REM sleep, percent time spent in REM sleep and REM sleep frequency/hr. Also, during probe test, the escape latency was significantly increased, and the percentage time spent in the platform quadrant were significantly decreased in both, Mus and Lox 2% treated rats, while the number of platform location crossings was decreased in Mus treated group. The results showed that Lox 2% and Mus into SC reduced consolidation of visuospatial learning. The findings support our contention that SC mediated activation of REMs exerts a positive influence in processing and consolidation of visual learning during REM sleep. The findings explain the role of REMs during REM sleep in visual memory consolidation.
PubMed: 37714322
DOI: 10.1016/j.physbeh.2023.114352 -
BioRxiv : the Preprint Server For... Sep 2023During learning, multi-dimensional inputs are integrated within the sensory cortices. However, the strategies by which the sensory cortex employs to achieve learning...
During learning, multi-dimensional inputs are integrated within the sensory cortices. However, the strategies by which the sensory cortex employs to achieve learning remains poorly understood. We studied the sensory cortical neuronal coding of trace eyeblink conditioning (TEC) in head-fixed, freely running mice, where whisker deflection was used as a conditioned stimulus (CS) and an air puff to the cornea delivered after an interval was used as unconditioned stimulus (US). After training, mice learned the task with a set of stereotypical behavioral changes, most prominent ones include prolonged closure of eyelids, and increased reverse running between CS and US onset. The local blockade of the primary somatosensory cortex (S1) activities with muscimol abolished the behavior learning suggesting that S1 is required for the TEC. In naive animals, based on the response properties to the CS and US, identities of the small proportion (~20%) of responsive primary neurons (PNs) were divided into two subtypes: CR (i.e. CS-responsive) and UR neurons (i.e. US-responsive). After animals learned the task, identity of CR and UR neurons changed: while the CR neurons are less responsive to CS, UR neurons gain responsiveness to CS, a new phenomenon we defined as 'learning induced neuronal identity switch (LINIS)'. To explore the potential mechanisms underlying LINIS, we found that systemic and local (i.e. in S1) administration of the nicotinic receptor antagonist during TEC training blocked the LINIS, and concomitantly disrupted the behavior learning. Additionally, we monitored responses of two types of cortical interneurons (INs) and observed that the responses of the somatostatin-expressing (SST), but not parvalbumin-expressing (PV) INs are negatively correlated with the learning performance, suggesting that SST-INs contribute to the LINIS. Thus, we conclude that L2/3 PNs in S1 encode perceptual learning by LINIS like mechanisms, and cholinergic pathways and cortical SST interneurons are involved in the formation of LINIS.
PubMed: 37693620
DOI: 10.1101/2023.08.30.555603 -
Toxicon : Official Journal of the... Sep 2023The genus Amanita sect. Amanita harbors approximately 150 species in the world, and 27 species have been recognized in China. Some of the species in China have...
The genus Amanita sect. Amanita harbors approximately 150 species in the world, and 27 species have been recognized in China. Some of the species in China have continuously caused poisoning. The responsible toxins should be ibotenic acid (IBO) and muscimol (MUS). However, species of the section Amanita containing IBO and MUS and their systematic positions are unclear. In this study, the contents of IBO and MUS in 84 samples of 24 species in section Amanita were detected using UPLC‒MS/MS, and the distribution of toxin-containing species in the molecular phylogeny was analyzed by the combined (ITS, nrLSU, RPB2, TUB2 and TEF1-α) dataset using maximum likelihood (ML) analysis and Bayesian inference (BI). Our results indicated that 10 of the 24 species contained IBO and MUS ranging from 0.6125 to 32.0932 and 0.0056-5.8685 g/kg dry weight, respectively. Among these 10 species, the toxins of eight species, including Amanita altipes, A. concentrica, A. flavopantherina, A. griseopantherina, A. pseudopantherina, A. rubrovolvata, A. subglobosa and A. sychnopyramis, were detected for the first time. In addition, the IBO and MUS contents of A. subglobosa in different growth stages showed that both toxins decreased in the mature stage. The phylogenetic analysis showed that all species of sect. Amanita from China were divided into 5 groups. And IBO- and MUS-containing species were gathered in clades Ⅰ and Ⅳ, but not all of the species in the two clades contain the toxins. No presence of IBO and MUS in the species of clades Ⅱ, Ⅲ and Ⅴ were confirmed.
Topics: Ibotenic Acid; Amanita; Bayes Theorem; Chromatography, Liquid; Muscimol; Phylogeny; Tandem Mass Spectrometry; China
PubMed: 37611670
DOI: 10.1016/j.toxicon.2023.107257 -
Regulation of vagally-evoked respiratory responses by the lateral parabrachial nucleus in the mouse.Respiratory Physiology & Neurobiology Oct 2023Vagal sensory inputs to the brainstem can alter breathing through the modulation of pontomedullary respiratory circuits. In this study, we set out to investigate the...
Vagal sensory inputs to the brainstem can alter breathing through the modulation of pontomedullary respiratory circuits. In this study, we set out to investigate the localised effects of modulating lateral parabrachial nucleus (LPB) activity on vagally-evoked changes in breathing pattern. In isoflurane-anaesthetised and instrumented mice, electrical stimulation of the vagus nerve (eVNS) produced stimulation frequency-dependent changes in diaphragm electromyograph (dEMG) activity with an evoked tachypnoea and apnoea at low and high stimulation frequencies, respectively. Muscimol microinjections into the LPB significantly attenuated eVNS-evoked respiratory rate responses. Notably, muscimol injections reaching the caudal LPB, previously unrecognised for respiratory modulation, potently modulated eVNS-evoked apnoea, whilst muscimol injections reaching the intermediate LPB selectively modulated the eVNS-evoked tachypnoea. The effects of muscimol on eVNS-evoked breathing rate changes occurred without altering basal eupneic breathing. These results highlight novel roles for the LPB in regulating vagally-evoked respiratory reflexes.
Topics: Animals; Mice; Respiratory Rate; Apnea; Muscimol; Parabrachial Nucleus; Tachypnea
PubMed: 37597796
DOI: 10.1016/j.resp.2023.104141 -
Die Naturwissenschaften Aug 2023We describe two large predators from the hominoid-bearing Khorat sand pits, Nakhon Ratchasima Province, northeastern Thailand: a new genus of pantherine,...
A new large pantherine and a sabre-toothed cat (Mammalia, Carnivora, Felidae) from the late Miocene hominoid-bearing Khorat sand pits, Nakhon Ratchasima Province, northeastern Thailand.
We describe two large predators from the hominoid-bearing Khorat sand pits, Nakhon Ratchasima Province, northeastern Thailand: a new genus of pantherine, Pachypanthera n. gen., represented by partial mandible and maxilla and an indeterminate sabre-toothed cat, represented by a fragment of upper canine. The morphological characters of Pachypanthera n. gen., notably the large and powerful canine, the great robustness of the mandibular body, the very deep fossa for the m. masseter, the zigzag HSB enamel pattern, indicate bone-cracking capacities. The genus is unique among Felidae as it has one of the most powerful and robust mandibles ever found. Moreover, it may be the oldest known pantherine, as other Asian pantherines are dated back to the early Pliocene. The taxa we report here are the only carnivorans known from the late Miocene of Thailand. Although the material is rather scarce, it brings new insights to the evolutionary history of Neogene mammals of Southeast Asia, in a geographic place which is partly "terra incognita."
Topics: Animals; Carnivora; Felidae; Fossils; Hominidae; Muscimol; Sand; Thailand
PubMed: 37584870
DOI: 10.1007/s00114-023-01867-4 -
IScience Aug 2023In the cerebro-cerebellar loop, outputs from the cerebral cortex are thought to be transmitted via monosynaptic corticopontine gray (PG) pathways and subsequently...
In the cerebro-cerebellar loop, outputs from the cerebral cortex are thought to be transmitted via monosynaptic corticopontine gray (PG) pathways and subsequently relayed to the cerebellum. However, it is unclear whether this pathway is used constitutively for cerebro-cerebellar transduction. We examined perioral sensory pathways by unit recording from Purkinje cells in ketamine/xylazine-anesthetized mice. Infraorbital nerve stimulations enhanced simple spikes (SSs) with short and long latencies (first and second peaks), followed by SS inhibition. The second peak and SS inhibition were suppressed by muscimol (a GABA agonist) injections into not only the PG but also the mesodiencephalic junction (MDJ). The pathway from the secondary somatosensory area (SII) to the MDJ, but not the cortico-PG pathway, transmitted the second peak signals. SS inhibition was processed in the SII and primary motor area. Thus, the indirect cortico-PG pathway, via the MDJ, is recruited for perioral sensory transduction.
PubMed: 37539042
DOI: 10.1016/j.isci.2023.107301