Contributions of the Nucleus Accumbens Shell in Mediating the Enhancement in Memory Following Noradrenergic Activation of Either the Amygdala or Hippocampus.

Erin C Kerfoot,Cedric L Williams

doi:10.3389/fphar.2018.00047

Abstract

The nucleus accumbens shell is a site of converging inputs during memory processing for emotional events. The accumbens receives input from the nucleus of the solitary tract (NTS) regarding changes in peripheral autonomic functioning following emotional arousal. The shell also receives input from the amygdala and hippocampus regarding affective and contextual attributes of new learning experiences. The successful encoding of affect or context is facilitated by activating noradrenergic systems in either the amygdala or hippocampus. Recent findings indicate that memory enhancement produced by activating NTS neurons, is attenuated by suppressing accumbens functioning after learning. This finding illustrates the significance of the shell in integrating information from the periphery to modulate memory for arousing events. However, it is not known if the accumbens shell plays an equally important role in consolidating information that is initially processed in the amygdala and hippocampus. The present study determined if the convergence of inputs from these limbic regions within the nucleus accumbens contributes to successful encoding of emotional events into memory. Male Sprague-Dawley rats received bilateral cannula implants 2 mm above the accumbens shell and a second bilateral implant 2 mm above either the amygdala or hippocampus. The subjects were trained for 6 days to drink from a water spout. On day 7, a 0.35 mA footshock was initiated as the rat approached the spout and was terminated once the rat escaped into a white compartment. Subjects were then given intra-amygdala or hippocampal infusions of PBS or a dose of norepinephrine (0.2 μg) previously shown to enhance memory. Later, all subjects were given intra-accumbens infusion of muscimol to functionally inactivate the shell. Muscimol inactivation of the accumbens shell was delayed to allow sufficient time for norepinephrine to activate intracellular cascades that lead to long-term synaptic modifications involved in forming new memories. Results show that memory improvement produced by infusing norepinephrine in either the amygdala or hippocampus is attenuated by interrupting neuronal activity in the shell 1 or 7 7 h following amygdala or hippocampus activation. These findings suggest that the accumbens shell plays an integral role modulating information initially processed by the amygdala and hippocampus following exposure to emotionally arousing events. Additionally, results demonstrate that the accumbens is involved in the long-term consolidation processes lasting over 7 h.

Highlights

In response to new learning episodes, the shell division of the accumbens receives a constellation of neural input from brain regions that encode separate attributes of novel experiences
Using a 2 × 2 × 2 analysis of variance (ANOVA) (BLA/HIPPx PBS/NE x NAC PBS/NAC Muscimol 1 h), it is possible to determine if animals given amygdala or hippocampus treatments perform differently in this task designed to assess the strength of the footshock representation in Experiment 1
Findings from anatomical and physiological studies revealed that amygdala and hippocampal inputs converge on single neurons in the accumbens shell (French and Totterdell, 2003), evidence suggesting that accumbens processing is necessary to integrate new learning experiences from these limbic areas into memory is scarce

Summary

Introduction

In response to new learning episodes, the shell division of the accumbens receives a constellation of neural input from brain regions that encode separate attributes of novel experiences These inputs include signals from brainstem nuclei representing physiological changes induced by the event, information from the amygdala regarding the affective appraisal of stimuli and representations of contextual and temporal relationships of the episode from the ventral hippocampus (Mogenson et al, 1980; Groenewegen et al, 1987; Meredith et al, 1990; Wang et al, 1992; Brog et al, 1993; Petrovich et al, 1996; Delfs et al, 1998; Al’bertin, 2003; French and Totterdell, 2003; Jongen-Relo et al, 2003; McGinty and Grace, 2009). The accumbens shell may be in a critical position to modulate information emanating from limbic structures that encode separate features of newly experienced events

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