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Review
. 2014 Jun:105:25-35.
doi: 10.1016/j.brainresbull.2013.12.012. Epub 2014 Jan 7.

Regulation of memory - from the adrenal medulla to liver to astrocytes to neurons

Paul E Gold  1
Affiliations
Review

Regulation of memory - from the adrenal medulla to liver to astrocytes to neurons

Paul E Gold. Brain Res Bull. 2014 Jun.

Abstract

Epinephrine, released into blood from the adrenal medulla in response to arousing experiences, is a potent enhancer of learning and memory processing. This review examines mechanisms by which epinephrine exerts its effects on these cognitive functions. Because epinephrine is largely blocked from moving from blood to brain, it is likely that the hormone's effects on memory are mediated by peripheral actions. A classic effect of epinephrine is to act at the liver to break down glycogen stores, resulting in increased blood glucose levels. The increase in blood glucose provides additional energy substrates to the brain to buttress the processes needed for an experience to be learned and remembered. In part, it appears that the increased glucose may act in the brain in a manner akin to that evident in the liver, engaging glycogenolysis in astrocytes to provide an energy substrate, in this case lactate, to augment neuronal functions. Together, the findings reveal a mechanism underlying modulation of memory that integrates the physiological functions of multiple organ systems to support brain processes. This article is part of a Special Issue entitled 'Memory enhancement'.

Keywords: Astrocytes; Brain metabolism and memory; Epinephrine; Glucose; Memory consolidation and modulation; Vagus.

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Conflict of interest statement

Conflict of Interest Statement

The author declares that there are no conflicts of interest regarding financial, personal, or organizational relationships that could inappropriately influence this work.

Figures

Figure 1
Figure 1
Enhancement of working memory in a spontaneous alternation task by L- and D-glucose, an artificial and natural sugar, respectively. In rats, a full dose-response curve for both sugars revealed optimal enhancement of memory at 3000 and 250 mg/kg for L- and D-glucose. Left graph: Enhancement of alternation scores with both sugars in rats that had undergone sham surgery for vagotomy. Right graph: Vagotomy blocked the enhancement of memory produced by L-glucose but did not block enhancement produced by the natural D-glucose. (GLU = glucose) (From Talley et al., 2002.)
Figure 2
Figure 2
Effects of food-restriction on the ability of epinephrine to enhance memory. In free-fed control rats, epinephrine (EPI) injections 30 min prior to behavioral testing enhanced memory on a spontaneous alternation task in an inverted-U dose-response manner. In contrast, epinephrine was less effective in rats whose food had been removed for the 24 hr before testing. (From Talley et al., 2000.)
Figure 3
Figure 3
Epinephrine effects on learning in place and response versions of food-motivated 4-arm radial mazes. In the place version of the maze, rats were trained to find food at the end of an arm located in a particular position relative to the room cues. In the response version of the maze, rats were trained to find food by using a specific body turn on each trial. A deceases in trials to criterion beyond control values indicates enhanced acquisition while an increase indicates impaired acquisition. Note that epinephrine did not enhance but instead impaired learning on these tasks. (From Sadowski et al., 2009.)
Figure 4
Figure 4
Effects of spontaneous alternation testing (during gray section of graph) on levels of glucose in the extracellular fluid (ECF) of the hippocampus, as measured with microdialysis procedures applied before, during, and after testing. Glucose levels remained generally constant in rats not tested on the maze (top line, blue ovals). Testing on a 4-arm alternation maze resulted in substantial and significant decreases in ECF glucose levels (bottom line, red diamonds). Testing a a 3-arm maze resulted in smaller decreases in glucose (middle line, green boxes); these values were significantly different than either controls or rats tested on the 4-arm maze. Because rats tested on the 3-arm maze had similar locomotor activity and exhibited alternation scores above baseline, the smaller decrease in glucose appears to be based on the different cognitive loads between the more-demanding 4-arm and less-demanding 3-arm mazes. (From McNay et al., 2000).
Figure 5
Figure 5
Effects of intrahippocampal glucose infusions on release of acetylcholine in the hippocampus before, during, and after spontaneous alternation testing. Note that spontaneous alternation testing resulted in increases in acetylcholine release (open circles). Intrahippocampal infusions of glucose augmented the magnitude of that release during memory testing. (From Ragozzino et al., 1998.)
Figure 6
Figure 6
Effects of spontaneous alternation testing on extracellular glucose (black diamonds) and lactate (gray circles) levels in the hippocampus. These levels were measured using bioprobes with 1-sec sampling periods, summarized here as 10-sec sampling epochs. Lactate in particular is largely provided to extracellular fluid and then to neurons from astrocytes after metabolism of glucose via glycolysis and/or breakdown of glycogen stores. Note first that glucose levels decreased during alternation testing, as shown before with microdialysis methods. Note also that lactate levels increased during testing, mirroring the changes in glucose. Not shown here, pharmacological manipulations that block and restore lactate availability impair and enhance memory, respectively. (From Newman et al., 2011.)
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