Harden, S. W. | bioRxiv Science

bioRxiv2019

Aging alters the role of basolateral amygdala in intertemporal choice

Aging is associated with an increased ability to delay gratification. Moreover, even when matched for performance, young and aged subjects recruit distinct brain circuitry to complete complex cognitive tasks. Experiments herein used an optogenetic approach to test whether altered recruitment of the basolateral amygdala (BLA), a brain region implicated in valuation of reward-cost contingencies, contributes to age-dependent changes in intertemporal decision making. BLA inactivation while rats deliberated prior to choices between options that yielded either small, immediate or large, delayed rewards rendered both young and aged rats less impulsive. In contrast, BLA inactivation after choices were made (during evaluation of choice outcomes) rendered young rats more impulsive but had no effect in aged rats. These data define multiple, temporally-discrete roles for BLA circuits in intertemporal decision making and implicate altered recruitment of BLA in the elevated preference for delayed rewards that is characteristic of advanced age. Impact StatementBasolateral amygdala (BLA) performs multiple, temporally-discrete functions during intertemporal decision making. Differential engagement of BLA contributes to the enhanced ability to delay gratification that is characteristic of advanced ages.

neuroscience↗

bioRxiv2019

Endogenous oxytocin inhibits hypothalamic stress responsive neurons following acute hypernatremia

Significant prior evidence indicates that centrally acting oxytocin robustly modulates stress responsiveness and anxiety-like behavior, although the neural mechanisms behind these effects are not completely understood. A plausible neural basis for oxytocin mediated stress reduction is via inhibition of corticotropin-releasing hormone (CRH) neurons in the paraventricular nucleus of the hypothalamus (PVN) that regulate activation of the hypothalamic-pituitary-adrenal (HPA) axis. Previously, we have shown that following subcutaneous injection of 2.0 M NaCl, oxytocin (OT) synthesizing neurons are activated in the rat PVN, an oxytocin receptor (Oxtr) dependent inhibitory tone develops on a subset of parvocellular neurons, and stress-mediated increases in plasma corticosterone levels are blunted. Here, we utilized transgenic male CRH-reporter mice to selectively target PVN CRH neurons for whole-cell recordings. These experiments reveal that acute salt loading produces tonic inhibition of PVN CRH neurons through a mechanism that is largely independent of synaptic activity. Further studies reveal that CRH neurons within the PVN synthesize mRNA for Oxtr(s). Salt induced Oxtr-dependent inhibitory tone was eliminated in individual PVN CRH neurons filled with GDP-{beta}-S, and was also largely absent in PVN CRH neurons extracted form CRH-Oxtr KO mice. Additional electrophysiological studies suggest that reduced excitability of PVN CRH neurons in salt loaded animals is associated with increased activation of an inwardly rectifying potassium channel. Collectively, these data reveal a likely cellular mechanism by which endogenous oxytocin signaling reduces the excitability of PVN CRH neurons to curb stress responsiveness during times of high plasma osmolality.

neuroscience↗