Age- and Sex-Dependent Changes in Locus Coeruleus Physiology and Anxiety-Like Behavior Following Acute Stressor Exposure

Abstract

Adolescence is a critical period of development with increased sensitivity toward psychological stressors. Many psychiatric conditions emerge during adolescence and animal studies have shown that that acute stress has long-term effects on hypothalamic-pituitary-adrenal axis function and behavior. We recently demonstrated that acute stress produces long-term electrophysiological changes in locus coeruleus and long-lasting anxiety-like behavior in adolescent male rats. Based on prior reports of increased stress sensitivity during adolescence and increased sensitivity of female locus coeruleus toward corticotropin releasing factor, we hypothesized that the same acute stressor would cause different behavioral and physiological responses in adolescent female and adult male and female rats one week after stressor exposure. In this study, we assessed age and sex differences in how an acute psychological stressor affects corticosterone release, anxiety-like behavior, and locus coeruleus physiology at short- and long-term intervals. All groups of animals except adult female responded to stress with elevated corticosterone levels at the acute time point. One week after stressor exposure, adolescent females showed decreased firing of locus coeruleus neurons upon current injection and increased exploratory behavior compared to controls. The results were in direct contrast to changes observed in adolescent males, which showed increased anxiety-like behavior and increased spontaneous and induced firing in locus coeruleus neurons a week after stressor exposure. Adult males and females were both behaviorally and electrophysiologically resilient to the long-term effects of acute stress. Therefore, there may be a normal developmental trajectory for locus coeruleus neurons which promotes stress resilience in adults, but stressor exposure during adolescence perturbs their function. Furthermore, while locus coeruleus neurons are more sensitive to stressor exposure during adolescence, the effect varies between adolescent males and females. These findings suggest that endocrine, behavioral, and physiological responses to stress vary among animals of different age and sex, and therefore these variables should be taken into account when selecting models and designing experiments to investigate the effects of stress. These differences in animals may also allude to age and sex differences in the prevalence of various psychiatric illnesses within the human population.

Sex differences in single neuron function and proteomics profiles examined by patch‐clamp and mass spectrometry in the locus coeruleus of the adult mouse

“…24 Later research delved into age-and sex-dependent variations in the physiology of LC neurons and anxiety-like behavior post-acute stressor exposure, but these studies maintained a within-group focus rather than comparing between groups. 25 Contrary to our observations, some research found no significant disparities in baseline action potential firing rates between sexes. However, upon injecting current into the neuron, F I G U R E 5 Differential protein expression and abundance in PC/SCP neurons from female and male mice.…”

“…Pioneering research focusing on the membrane properties of LC neurons did not clarify the age and gender of the rats used in the experiments 24 . Later research delved into age‐ and sex‐dependent variations in the physiology of LC neurons and anxiety‐like behavior post‐acute stressor exposure, but these studies maintained a within‐group focus rather than comparing between groups 25 . Contrary to our observations, some research found no significant disparities in baseline action potential firing rates between sexes.…”

Drop dead! Female mate avoidance in an explosively breeding frog

“…Anyhow, what the proximate factor killing the females may be, tonic immobility may be a better option for a female than fighting her way out of the amplexus, as any movement in a large mating group automatically attracts attention of further nearby males and thus increases the probability of a mating ball formation. With these considerations in mind, it would be interesting to measure stress corticosterone levels in female R. temporaria and investigate how they correspond to age and sex ratio in breeding aggregations [45,48]. Future studies should consider investigating different frog densities, sex ratios and age classes, to test for mate choice and the potential costs associated with reproduction.…”

Locus Coeruleus Neurons’ Firing Pattern Is Regulated by ERG Voltage-Gated K+ Channels

“…Located in the anterior pons, the locus coeruleus (LC), with its extensive innervations throughout the central nervous system, is the major noradrenergic nucleus of the brain and thereby controls a broad range of physiological processes that include cognition, learning and memory, sleep–wake cycle, arousal, attention, mood, anxiety and pain [ 1 , 2 , 3 , 4 , 5 , 6 , 7 ]. These and other neurophysiological processes are known to be affected by changes in the discharge properties of LC neurons [ 7 ], which in turn are dependent on the intrinsic membrane properties and the ion channel constituents of these neurons.…”