Reversal of aging‐related emotional memory deficits by norepinephrine via regulating the stability of surfaceAMPAreceptors

Abstract

Aging-related emotional memory deficit is a well-known complication in Alzheimer's disease and normal aging. However, little is known about its molecular mechanism. To address this issue, we examined the role of norepinephrine (NE) and its relevant drug desipramine in the regulation of hippocampal long-term potentiation (LTP), surface expression of AMPA receptor, and associative fear memory in rats. We found that there was a defective regulation of NE content and AMPA receptor trafficking during fear conditioning, which were accompanied by impaired emotional memory and LTP in aged rats. Furthermore, we also found that the exogenous upregulation of NE ameliorated the impairment of LTP and emotional memory via enhancing AMPA receptor trafficking in aged rats, and the downregulation of NE impaired LTP in adult rats. Finally, acute treatment with NE or desipramine rescued the impaired emotional memory in aged rats. These results imply a pivotal role for NE in synaptic plasticity and associative fear memory in aging rats and suggest that desipramine is a potential candidate for treating aging-related emotional memory deficit.

Fear Memory

“…Accordingly, most recent data agree with the overwhelming previous evidence (401,403,404) that NE in the BLA has a stimulant or facilitatory physiological role on memory modulation (170,366) and a stimulant influence on fear memory in particular (195,311,590,631).…”

Emotional arousal and recognition memory are differentially reflected in pupil diameter responses during emotional memory for negative events in younger and older adults

“…Studies in humans, rats as well as primates suggest that a reduction of noradrenergic modulation during ageing can be relevant for altered cognitive functions (Arnsten and Golman-Rakic, 1985;Clewett et al, 2016;Mann, 1983), including memory for negative emotional events (Luo et al, 2015). On the other hand, imaging studies which show increased prefrontal and decreased amygdala activation during negative events in older adults suggest that older adults actively downregulate their arousal response to negative events (see Mather, 2016 for a review).…”

“…This is the case for more complex episodic memory contents as well as negative emotional memory events (Jacques et al, 2009;Naveh-Benjamin et al, 2003). A recent study in rats showed that an agerelated deficit in negative emotional memory formation is accompanied by reduced levels of extracellular noradrenaline and can be attenuated by administrating noradrenaline or blocking noradrenaline reuptake (Luo et al, 2015). Here we investigated whether physiological indicators of LC activation can inform age differences in emotional memory for negative events.…”

Dysfunctional Sensory Modalities, Locus Coeruleus, and Basal Forebrain: Early Determinants that Promote Neuropathogenesis of Cognitive and Memory Decline and Alzheimer’s Disease

“…Hence, NE is linked to wakefulness, sustained attention, and improved cognitive and behavioral performance (Aston- Jones et al 1991;Rajkowski et al 1994;Devilbiss and Waterhouse 2004;Berridge et al 2012). NE-dependent modulation of gene transcription, synaptic strength, and other processes clearly reflects a potentially critical role in neuraxis homeostasis (Berridge and Waterhouse 2003;Luo et al 2015). However, there is a progressive atrophy and decline of LC/NE system in aging (Adolfsson et al 1979;Mann et al 1983;Tomonaga 1983;Grudzien et al 2007;Mouton et al 2012).…”

“…A defective regulation of NE content occurs in impaired emotional memory in aged rats (Luo et al 2015). Downregulation of NE impairs LTP in adult rats, whereas upregulation of NE ameliorates this impairment and emotional memory (via enhancing AMPA receptor trafficking) in the aged rats (Luo et al 2015).…”