Biology subjects

Thayer, J. F.

Publications and source records attributed to Thayer, J. F..

4 recordsLinked to original sources

bioRxiv2022

Site-Specific Knockdown of Microglia in the Locus Coeruleus Regulates Hypervigilant Responses to Social Stress in Female Rats

BackgroundWomen are at increased risk for psychosocial stress-related anxiety disorders, yet mechanisms regulating this risk are unknown. Psychosocial stressors activate microglia, and the resulting neuroimmune responses that females exhibit heightened sensitivity to may serve as an etiological factor in their elevated risk. However, studies examining the role of microglia during stress in females are lacking. MethodsMicroglia were manipulated in the stress-sensitive locus coeruleus (LC) of female rats in the context of social stress in two ways. First, intra-LC lipopolysaccharide (LPS; 0 or 3g/side, n=5-6/group), a potent TLR4 agonist and microglial activator, was administered. One hour later, rats were exposed to control or an aggressive social defeat encounter between two males (WS, 15-min). In a separate study, females were treated with intra-LC or intra-central amygdala mannosylated liposomes containing clodronate (m-CLD; 0 or 25g/side, n=13-14/group), a compound toxic to microglia. WS-evoked burying, cardiovascular responses, and sucrose preference were measured. Brain and plasma cytokines were quantified, and cardiovascular telemetry assessed autonomic balance. ResultsIntra-LC LPS augmented the WS-induced burying response and increased plasma corticosterone and interleukin-1{beta} (IL-1{beta}). Further, the efficacy and selectivity of microinjected m-CLD was determined. In the context of WS, intra-LC m-CLD attenuated the hypervigilant burying response during WS as well as the accumulation of intra-LC IL-1{beta}. Intra-central amygdala m-CLD had no effect on witness stress-evoked behavior. ConclusionsThese studies highlight an innovative method for depleting microglia in a brain region specific manner and indicate that microglia in the LC differentially regulate hypervigilant WS-evoked behavioral and autonomic responses. HIGHLIGHTSO_LIIntra-LC LPS augments behavioral and physiological responses to social stress C_LIO_LIMannosylated liposomal clodronate site-specifically reduces microglial expression C_LIO_LIMicroglia within the locus coeruleus regulate stress-evoked behavior in female rats C_LI

neuroscience↗

bioRxiv2022

Associations between locus coeruleus MRI contrast and physiological responses to acute stress in younger and older adults

Acute stress activates the brains locus coeruleus (LC)-noradrenaline system. Recent studies indicate that a magnetic resonance imaging (MRI)-based measure of LC structure is associated with better cognitive outcomes in later life. Yet despite the LCs documented role in promoting physiological arousal during acute stress, no studies have examined whether MRI-assessed LC structure is related to arousal responses to acute stress. In this study, 102 younger and 51 older adults completed an acute stress induction task while we assessed multiple measures of physiological arousal (heart rate, breathing rate, systolic and diastolic blood pressure, sympathetic tone, and heart rate variability, HRV). We used turbo spin echo MRI scans to quantify LC MRI contrast as a measure of LC structure. We applied univariate and multivariate approaches to assess how LC MRI contrast was associated with arousal at rest and during acute stress reactivity and recovery. In older participants, having higher caudal LC MRI contrast was associated with greater stress-related increases in systolic blood pressure and decreases in HRV, as well as lower HRV during recovery from acute stress. These results suggest that having higher caudal LC MRI contrast in older adulthood is associated with more pronounced physiological responses to acute stress. Further work is needed to confirm these patterns in larger samples of older adults.

neuroscience↗

bioRxiv2021

Emotion Down- and Up-Regulation Act on Spatially Distinct Brain Areas:Interoceptive Regions to Calm Down and Other Affective Regions to Amp Up

Prior studies on emotion regulation identified a set of brain regions specialized for generating and controlling affect. Researchers generally agree that when up- and down-regulating emotion, control regions in the prefrontal cortex turn up or down activity in affect-generating areas. However, the assumption that turning up and down emotions produces opposite effects in the same affect-generating regions is untested. We call this assumption the affective dial hypothesis. Our study tested this hypothesis by examining the overlap between the sets of regions activated during up-regulation and those deactivated during down-regulation in a large number of participants (N=105). We found that up- and down-regulation both recruit regulatory regions such as the inferior frontal gyrus and dorsal anterior cingulate gyrus but act on distinct affect-generating regions. While up-regulation increases BOLD signal in regions associated with emotion such as the amygdala, anterior insula, striatum and anterior cingulate gyrus as well as in regions associated with sympathetic vascular activity such as periventricular white matter, down-regulation decreases signal in regions receiving interoceptive input such as the posterior insula and postcentral gyrus. These findings indicate that up- and down-regulation do not generally exert opposing effects on the same affect-generating regions. Instead, they target different brain circuits. Significance StatementMany contexts require modulating ones own emotions. Identifying the brain areas implementing these regulatory processes should advance understanding emotional disorders and designing potential interventions. The emotion regulation field has an implicit assumption we call the affective dial hypothesis: that both emotion up- and down-regulation modulate the same emotion-generating brain areas. Countering the hypothesis, our findings indicate that up- and down-modulating emotions target different brain areas. Thus, the mechanisms underlying emotion regulation differ more than previously appreciated for up- versus down-regulation. In addition to their theoretical importance, these findings are critical for researchers attempting to target activity in particular brain regions during an emotion regulation intervention.

neuroscience↗

bioRxiv2021

Cardiac sympathovagal activity initiates a functional brain-body response to emotional processing

A century-long debate on bodily states and emotions persists. While the involvement of bodily activity in emotion physiology is widely recognized, the specificity and causal role of such activity related to brain dynamics has not yet been demonstrated. We hypothesize that the peripheral neural monitoring and control of cardiovascular activity prompts and sustains brain dynamics during an emotional experience, so these afferent inputs are processed by the brain by triggering a concurrent efferent information transfer to the body. To this end, we investigated the functional brain-heart interplay under emotion elicitation in publicly available data from 62 healthy participants using a computational model based on synthetic data generation of EEG and ECG signals. Our findings show that sympathovagal activity plays a leading and causal role in initiating the emotional response, in which ascending modulations from vagal activity precede neural dynamics and correlate to the reported level of arousal. The subsequent dynamic interplay observed between the central and autonomic nervous systems sustains emotional processing. These findings should be particularly revealing for the psychophysiology and neuroscience of emotions. SignificanceWe investigate the temporal dynamics of brain and cardiac activities in healthy subjects who underwent an emotional elicitation through videos. We demonstrate that, within the first few seconds, emotional stimuli modulate the heart activity, which in turn stimulate an emotion-specific cortical response in the brain. Then, the conscious emotional experience is sustained by a bidirectional brain-heart interplay and information exchange. Moreover, the perceived intensity of an emotional stimulus is predicted by the intensity of neural control regulating the heart activity. These findings may constitute the fundamental knowledge linking neurophysiology and psychiatric disorders, including the link between depressive symptoms and cardiovascular disorders.

neuroscience↗