Abstract
Intrinsic neuronal excitability has been reported to change during normal aging. The bed nucleus of the stria terminalis (BNST), a limbic forebrain structure, is involved in fear, stress and anxiety; behavioral features that exhibit age-dependent properties. To examine the effect of aging on intrinsic neuronal properties in BNST we compared patch clamp recordings from cohorts of female mice at two ages, 3–4 months (Young) and 29–30 months (Aged) focusing on 2 types of BNST neurons. Aged Type I neurons exhibited a hyperpolarized resting membrane potential (RMP) of circa -80 mV compared to circa -70 mV in the Young. A key finding in this study is a hyper-excitability of Type II neurons with age reflected in an increase in firing frequency in response to depolarizing current injections; activation of Type II neurons is believed to dampen anxiety like responses. Such age-related changes in intrinsic neurophysiological function are likely to modulate how the limbic system, acting via BNST, shapes function in the HPA-axis.
Highlights
Chronic stress, anxiety and related mood disorders have a substantial effect on the well-being of all global societies
A total of 28 cells from the aged 29–30 months (Aged) cohort and 43 cells from the Young cohort were recorded in the BNSTALG
Cells were placed into current clamp to examine properties at their resting membrane potential; the mean resting membrane potential of the young cohort (−68 ± 3 mV, n = 18) was over 10 mV more depolarized than that of the Aged population
Summary
Anxiety and related mood disorders have a substantial effect on the well-being of all global societies. Seen at most ages from childhood onward, the development and nature of chronic stress exhibits a complex age-related nature (Garrido, 2011; Prenderville et al, 2015) the basis of which is not fully understood. Many physiological manifestations of stress-related disorders are affected via the hypothalamus. This includes the classical neuroendocrine hypothalamopituitary-adrenocortical (HPA) axis, alongside a range of other neural circuits for example hypothalamic control of various brainstem nuclei that mediate peripheral homeostatic responses such as blood pressure regulation. Stress-eliciting neural drive, is thought typically to have it genesis in higher centers, in particular the circuits of the limbic system which are known to integrate multiple complex factors to shape emotion and mood
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