Angiotensinergic Neurotransmissions in the Medial Amygdala Nucleus Modulate Behavioral Changes in the Forced Swimming Test Evoked by Acute Restraint Stress in Rats.

We investigated the role of angiotensin II type 1 (AT1 receptor) and type 2 (AT2 receptor) and MAS receptors present in the medial amygdaloid nucleus (MeA) in behavioral changes in the forced swimming test (FST) evoked by acute restraint stress in male rats. For this, rats received bilateral microinjection of either the selective AT1 receptor antagonist losartan, the selective AT2 receptor antagonist PD123319, the selective MAS receptor antagonist A-779, or vehicle 10 min before a 60 min restraint session. Then, behavior in the FST was evaluated immediately after the restraint (15 min session) and 24 h later (5 min session). The behavior in the FST of a non-stressed group was also evaluated. We observed that acute restraint stress decreased immobility during both sessions of the FST in animals treated with vehicle in the MeA. The decreased immobility during the first session was inhibited by intra-MeA administration of PD123319, whereas the effect during the second session was not identified in animals treated with A-779 into the MeA. Microinjection of PD123319 into the MeA also affected the pattern of active behaviors (i.e., swimming and climbing) during the second session of the FST. Taken together, these results indicate an involvement of angiotensinergic neurotransmissions within the MeA in behavioral changes in the FST evoked by stress.

Prenatal bisphenol A exposure is associated with medial amygdala neuron hyperresponsiveness to predator odor in rats.

Perinatal exposure to bisphenol A (BPA) causes several alterations in brain function and behavior. In previous studies, we showed that prenatal treatment with low-level BPA impaired gender-specific behavior, enhanced depression-like behavior, and augmented behavioral responses to predator odor in rats. On this premise, we hypothesized that BPA-treated rats were more susceptible to predator odor stress. To test the potential neural mechanism underlying this effect, we conducted an electrophysiological study of neurons in the medial amygdala-a regional component of the olfactory pathway with high estrogen and androgen receptor expression, and thus a potential target of BPA-in rats exposed to BPA. Extracellular recordings were obtained during the presentation of 3 plant odors and 3 predator odorants. Odor-responsive neurons in BPA-exposed rats showed greater activity in response to fox odor than did those in control rats. This finding complements the results of our previous behavioral study in which BPA-exposed rats exhibited enhanced avoidance behavior in response to fox odor. Given the close relationship between olfactory signaling and the stress response system, we suspect that BPA modifies the olfactory pathway at the level of the medial amygdala and thus modulates the corresponding stress response.

Posterodorsal Medial Amygdala Mediates Tail-Pinch Induced Food Intake in Female Rats.

Comfort eating during periods of stress is a common phenomenon observed in both animals and humans. However, the underlying mechanisms of stress-induced food intake remain elusive. The amygdala plays a central role in higher-order emotional processing and the posterodorsal subnucleus of the medial amygdala (MePD), in particular, is involved in food intake. Extra-hypothalamic corticotrophin-releasing factor (CRF) is well recognised for mediating behavioural responses to stress. To explore the possible role of amygdala CRF receptor activation in stress-induced food intake, we evaluated whether a stressor such as tail-pinch, which reliably induces food intake, would fail to do so in animals bearing bilateral neurotoxic lesions of the MePD. Our results showed that ibotenic acid induced lesions of the MePD markedly reduced tail-pinch induced food intake in ovariectomised, 17ß-oestradiol replaced rats. In addition, intra-MePD (right side only) administration of CRF (0.002 or 0.02 ng) via chronically implanted cannulae resulted in a dose-dependent increase in food intake, although higher doses of 0.2 and 2 ng CRF had less effect, producing a bell shaped curve. Furthermore, intra-MePD (bilateral) administration of the CRF receptor antagonist, astressin (0.3 µg per side) effectively blocked tail-pinch induced food intake. These data suggest that the MePD is involved in stress-induced food intake and that the amygdala CRF system may be a mediator of comfort eating.

Altered superficial amygdala-cortical functional link in resting state after 36 hours of total sleep deprivation.

The superficial amygdala (SFA) is important in human emotion/affective processing via its strong connection with other limbic and cerebral cortex for receptive and expressive emotion processing. Few studies have investigated the functional connectivity changes of the SFA under extreme conditions, such as prolonged sleep loss, although the SFA showed a distinct functional connectivity pattern throughout the brain. In this study, resting-state functional magnetic resonance imaging (rs-fMRI) was employed to investigate the changes of SFA-cortical functional connectivity after 36 hr of total sleep deprivation (TSD). Fourteen healthy male volunteers aged 25.9 ± 2.3 years (range 18-28 years) enrolled in this within-subject crossover study. We found that the right SFA showed increased functional connectivity with the right medial prefrontal cortex (mPFC) and decreased functional connectivity with the right dorsal posterior cingulate cortex (dPCC) in the resting brain after TSD compared with that during rested wakefulness. For the left SFA, decreased connectivity with the right dorsal anterior cingulate cortex (dACC) and right dPCC was found. Further regression analysis indicated that the functional link between mPFC and SFA significantly correlated with the Profile of Mood State scores. Our results suggest that the amygdala cannot be treated as a single unit in human neuroimaging studies and that TSD may alter the functional connectivity pattern of the SFA, which in turn disrupts emotional regulation.

Hemodynamic and EEG Time-Courses During Unilateral Hand Movement in Patients with Cortical Myoclonus. An EEG-fMRI and EEG-TD-fNIRS Study.

Multimodal human brain mapping has been proposed as an integrated approach capable of improving the recognition of the cortical correlates of specific neurological functions. We used simultaneous EEG-fMRI (functional magnetic resonance imaging) and EEG-TD-fNIRS (time domain functional near-infrared spectroscopy) recordings to compare different hemodynamic methods with changes in EEG in ten patients with progressive myoclonic epilepsy and 12 healthy controls. We evaluated O2Hb, HHb and Blood oxygen level-dependent (BOLD) changes and event-related desynchronization/synchronization (ERD/ERS) in the α and ß bands of all of the subjects while they performed a simple motor task. The general linear model was used to obtain comparable fMRI and TD-fNIRS activation maps. We also analyzed cortical thickness in order to evaluate any structural changes. In the patients, the TD-NIRS and fMRI data significantly correlated and showed a significant lessening of the increase in O2Hb and the decrease in BOLD. The post-movement ß rebound was minimal or absent in patients. Cortical thickness was moderately reduced in the motor area of the patients and correlated with the reduction in the hemodynamic signals. The fMRI and TD-NIRS results were consistent, significantly correlated and showed smaller hemodynamic changes in the patients. This finding may be partially attributable to mild cortical thickening. However, cortical hyperexcitability, which is known to generate myoclonic jerks and probably accounts for the lack of EEG ß-ERS, did not reflect any increased energy requirement. We hypothesize that this is due to a loss of inhibitory neuronal components that typically fire at high frequencies.

Blocking the mineralocorticoid receptor in humans prevents the stress-induced enhancement of centromedial amygdala connectivity with the dorsal striatum.

Two research lines argue for rapid stress-induced reallocations of neural network activity involving the amygdala. One focuses on the role of norepinephrine (NE) in mediating a shift towards the salience network and improving vigilance processing, whereas the other focuses on the role of cortisol in enhancing automatic, habitual responses. It has been suggested that the mineralocorticoid receptor (MR) is critical in shifting towards habitual responses, which are supported by the dorsal striatum. However, until now it remained unclear whether these two reallocations of neural recourses might be part of the same phenomenon and develop immediately after stress onset. We combined methods used in both approaches and hypothesized specifically that stress would lead to rapidly enhanced involvement of the striatum as assessed by amygala-striatal connectivity. Furthermore, we tested the hypothesis that this shift depends on cortisol interacting with the MR, by using a randomized, placebo-controlled, full-factorial, between-subjects design with the factors stress and MR-blockade (spironolactone). We investigated 101 young, healthy men using functional magnetic resonance imaging after stress induction, which led to increased negative mood, heart rate, and cortisol levels. We confirmed our hypothesis by revealing a stress-by-MR-blockade interaction on the functional connectivity between the centromedial amygdala (CMA) and the dorsal striatum. Stress rapidly enhanced CMA-striatal connectivity and this effect was correlated with the stress-induced cortisol response, but required MR availability. This finding might suggest that the stress-induced shift described by distinct research lines might capture different aspects of the same phenomenon, ie, a reallocation of neural resources coordinated by both NE and cortisol.