Making memories matter

Abstract

This article reviews some of the neuroendocrine bases by which emotional events regulate brain mechanisms of learning and memory. In laboratory rodents, there is extensive evidence that epinephrine influences memory processing through an inverted-U relationship, at which moderate levels enhance and high levels impair memory. These effects are, in large part, mediated by increases in blood glucose levels subsequent to epinephrine release, which then provide support for the brain processes engaged by learning and memory. These brain processes include augmentation of neurotransmitter release and of energy metabolism, the latter apparently including a key role for astrocytic glycogen. In addition to up- and down-regulation of learning and memory in general, physiological concomitants of emotion and arousal can also switch the neural system that controls learning at a particular time, at once improving some attributes of learning and impairing others in a manner that results in a change in the strategy used to solve a problem.

Keywords: arousal; emotion; epinephrine; glucose; learning strategy; memory.

Figure 1

Scheme for modulation of memory by epinephrine and glucose. A neutral event fails to initiate the release of epinephrine, resulting in absence of the biological steps downstream from an increase in circulating epinephrine levels. As a result, the memory for a neutral event is weak and rapidly forgotten. In contrast, an arousing event results in increases in epinephrine released from the adrenal medulla. The epinephrine in turn initiates glycogen breakdown to glucose in the liver, with increases in blood glucose levels. Glucose enters the brain, providing support for neurotransmitter release, activation of intracellular signals responding to receptor binding, with eventual enhancement of memory.

Figure 2

Epinephrine and glucose enhancement of memory in rats. Rats were trained in a one-trial inhibitory avoidance task, received injections of saline, epinephrine, or glucose immediately after training, and were tested 24 h later. Note the inverted-U dose-response curves for enhancement of memory seen on the test trial. Note also that injections of epinephrine or glucose 1 h after training did not significantly enhance memory on tests 24 h later. Under other conditions, e.g., training with a higher footshock, high doses of epinephrine, and glucose impair memory (Left from Gold and van Buskirk, ; Right from Gold, 1986).

Figure 3

Extracellular lactate and glucose levels in the hippocampus, measured before, during, and after behavioral testing. Using lactate- and glucose-specific biosensors, extracellular concentrations of both lactate and glucose were measured during spontaneous alternation testing. Lactate concentrations increased significantly at the beginning of behavioral testing. In contrast, glucose concentrations decreased after 5 min on the task. The increase in extracellular glucose seen 5–10 min after the start of memory testing corresponds to an increase in blood glucose levels. After the rat was removed from the maze there was a significant increase in lactate compared to baseline levels most likely due to handling (From Newman et al., 2011).

Figure 4

Number of trials to reach criterion on the place and response task after no treatment or single restraint stress ending 30 min prior to training. ANOVAS revealed a significant interaction of task by treatment. Pre-training single stress impaired learning on the place task and significantly enhanced learning on the response task (From Sadowski et al., 2009).