Interactions between brainstem noradrenergic neurons and the nucleus accumbens shell in modulating memory for emotionally arousing events

Abstract

The nucleus accumbens shell (NAC) receives axons containing dopamine-b-hydroxylase that originate from brainstem neurons in the nucleus of the solitary tract (NTS). Recent findings show that memory enhancement produced by stimulating NTS neurons after learning may involve interactions with the NAC. However, it is unclear whether these mnemonic effects are mediated by norepinephrine (NE) release from NTS terminals onto NAC neurons. The present studies approached this question by examining the contribution of NAC a-noradrenergic receptors in mediating this effect and assessed whether glutamatergic activation of the NTS alters NE concentrations in the NAC. Rats were trained for 6 d to drink from a water spout located at the end of an inhibitory avoidance chamber. On day 7, a 0.35-mA footshock was initiated once the rat approached the spout and remained active until it escaped into the neutral compartment. Blockade of a-noradrenergic receptors in the NAC with phentolamine (0.5 mg/0.5 mL) attenuated memory enhancement produced by glutamatergic (50 ng/0.5 mL) infusion on NTS neurons (P , 0.01). Experiment 2 used in vivo microdialysis to assess whether glutamate activation of NTS alters NAC NE concentrations. NE levels were unchanged by NTS infusion of phosphate-buffered saline (PBS) or low dose glutamate (50 ng/0.5 mL) but elevated significantly (P , 0.05) by combining the same dose with the footshock (0.35 mA, 2 sec) given in Study 1 or infusion of (100 ng/0.5 mL) glutamate alone. Findings demonstrate that NE released from NTS terminals enhances representations in memory by acting on a-noradrenergic receptors within the NAC.The shell division of the nucleus accumbens (NAC) receives highly processed information regarding affective and contextual features of new learning experiences from the amygdala and hippocampus, respectively (Mogenson et al. 1980;Groenewegen et al. 1987;Meredith et al. 1990;Wang et al. 1992;Brog et al. 1993;Petrovich et al. 1996;French and Totterdell 2003). These limbic inputs are complemented by norepinephrine containing axons supplied by the A2 class of noradrenergic neurons housed in the brainstem region of the nucleus of the solitary tract (NTS) (Delfs et al. 1998). Norepinephrine release from A2 NTS neurons play an important role in conveying information regarding experience-induced changes in the physiological state of the organism.The A2 neurons are activated during times of heightened arousal by the release of glutamate from vagal nerve fibers that ascend from the periphery to the brainstem (Allchin et al. 1994;King and Williams 2009). Highly arousing events increase epinephrine secretion from the adrenals and facilitate binding to b-adrenergic receptors along the vagus nerve (Lawrence et al. 1995) that in turn, increase impulse flow to brainstem neurons in the NTS (Lawrence et al. 1995;Miyashita and Williams 2006). Epinephrine administration, stimulation of the vagus nerve or direct infusion of glutamate onto A2 NTS neurons are all known to significantly potentiate norepinephrine release ...

Conditional viral tracing reveals that steroidogenic factor 1‐positive neurons of the dorsomedial subdivision of the ventromedial hypothalamus project to autonomic centers of the hypothalamus and hindbrain

“…Thus, these functional studies in combination with our anatomical findings suggest that the VMH may modulate cardiovascular function via innervation of the NTS. Intriguingly, TH‐positive noradrenergic neurons of the NTS interact with neurons of the nucleus accumbens to enhance memories for emotionally arousing events (Kerfoot et al, ; Kerfoot and Williams, ). Furthermore, glutamatergic transmission within the NTS has been demonstrated to strengthen fear memories via noradrenergic modulation of the amygdala (Miyashita and Williams, ).…”

Interacting brain systems modulate memory consolidation

“…Other studies provide additional evidence that increased glutamate transmission in the NTS enhances memory for emotionally arousing experiences. For instance, posttraining microinjections of glutamate into the NTS, where its neurons synapse with vagal afferents, improves memory for inhibitory avoidance (Kerfoot et al, 2008; Kerfoot and Williams, 2011; Miyashita and Williams, 2002), and also produces significant and long-lasting increases in norepinephrine concentrations sampled from the amygdala (Miyashita and Williams, 2002). …”

Generalized Poincaré plots analysis of heart period dynamics in different physiological conditions: Trained vs. untrained men

“…In the running conditions, oscillatory nature of sympathetic nervous system that dominates heart rate control in running is abolished and in this condition of steady-state its nature becomes more linear with a high absolute value [22]. This is also in accordance with the elongated shape of the trajectories.…”