Kelly, K. B. | Search bioRxiv

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↗

bioRxiv2017

Optogenetic inhibition reveals distinct roles for basolateral amygdala activity at discrete timepoints during risky decision making

Decision making is a multifaceted process, consisting of several distinct phases that likely require different cognitive operations. Previous work showed that the basolateral amygdala (BLA) is a critical substrate for decision making involving risk of punishment; however, it is unclear how the BLA is recruited at different stages of the decision process. To this end, the current study used optogenetics to inhibit the BLA during specific task phases in a model of risky decision making (Risky Decision-making Task; RDT) in which rats choose between a small, \"safe\" reward and a large reward accompanied by varying probabilities of footshock punishment. Rats received intra-BLA microinjections of viral vectors carrying either halorhodopsin (eNpHR3.0-mCherry) or mCherry alone (control) followed by optic fiber implants and were trained in the RDT. Laser stimulation during the task occurred during either intertrial interval, deliberation, or reward outcome phases, the latter of which was further divided into the three possible outcomes (small, safe; large, unpunished; large, punished). Inhibition of the BLA selectively during the deliberation phase decreased choice of the large, risky outcome (decreased risky choice). In contrast, BLA inhibition selectively during delivery of the large, punished outcome increased risky choice. Inhibition had no effect during the other phases, nor did it affect performance in control rats. Collectively, these data indicate that the BLA can either inhibit or promote choice of risky options, depending on the phase of the decision process in which it is active.\n\nSignificance StatementTo date, most behavioral neuroscience research on neural mechanisms of decision making has employed techniques that preclude assessment of distinct phases of the decision process. Here we show that optogenetic inhibition of the basolateral amygdala (BLA) has opposite effects on choice behavior in a rat model of risky decision making depending on the phase in which inhibition occurs. BLA inhibition during a period of deliberation between small, safe and large, risky outcomes decreased risky choice. In contrast, BLA inhibition during receipt of the large, punished outcome increased risky choice. These findings highlight the importance of temporally targeted approaches to understand neural substrates underlying complex cognitive processes. More importantly, they reveal novel information about dynamic BLA modulation of risky choice.

neuroscience↗