Modulation of multiple memory systems: From neurotransmitters to metabolic substrates

Abstract

This article reviews evidence showing that neurochemical modulators can regulate the relative participation of the hippocampus and striatum in learning and memory tasks. For example, relative release of acetylcholine increases in the hippocampus and striatum reflects the relative engagement of these brain systems during learning of place and response tasks. Acetylcholine release is regulated in part by available brain glucose levels, which themselves are dynamically modified during learning. Recent findings suggest that glucose acts through astrocytes to deliver lactate to neurons. Brain glycogen is contained in astrocytes and provides a capacity to deliver energy substrates to neurons when needed, a need that can be generated by training on tasks that target hippocampal and striatal processing mechanisms. These results integrate an increase in blood glucose after epinephrine release from the adrenal medulla with provision of brain energy substrates, including lactate released from astrocytes. Together, the availability of peripheral and central energy substrates regulate the processing of learning and memory within and across multiple neural systems. Dysfunctions of the physiological steps that modulate memory-from hormones to neurotransmitters to metabolic substrates-may contribute importantly to some of the cognitive impairments seen during normal aging and during neurodegenerative diseases. V C 2013 Wiley Periodicals, Inc.

Differential effects of massed and spaced training on place and response learning: A memory systems perspective

“…In addition, in view of the present findings, the question arises whether the gradual learning subserved by the DLS may be a function of number of trials, passage of time, or both. It may be speculated that the mere "passage of time" allotted by either a spaced training protocol or "extended training" protocol with many trials may be sufficient to allow for the gradual rise in striatal acetylcholine, as well as other temporally graded neurobiological processes (Gold et al, 2013), that may facilitate response learning and/or impair place learning. It is also possible that these factors are not mutually exclusive and that an interaction between number of trials and passage of time may govern the relative dominance of multiple memory systems.…”

The metabolic trinity, glucose–glycogen–lactate, links astrocytes and neurons in brain energetics, signaling, memory, and gene expression

“…Gold and colleagues demonstrated that systemic or central glucose administration enhanced cognitive performance and memory in rats, and glucose had a high positive impact on patients with Alzheimer's disease and Down's syndrome [26]. In addition, an essential role for glycogenolysis in memory processing was demonstrated by inhibition of glycogen phosphorylase with 1,4-dideoxy-1,4-amino-d-arabinitol (DAB) [23,48,64], and this conclusion is strongly reinforced by discovery of defects in long term memory formation in mice lacking brain glycogen synthase [20].…”

Regulation of memory – From the adrenal medulla to liver to astrocytes to neurons

“…There is considerable evidence that acetylcholine release contributes to a wide range of learning and memory categories, regulating the participation of multiple neural systems during cognitive processing (Gold et al, 2013). The examination of glucose effects on acetylcholine release has been assessed in the hippocampus in relation to both spontaneous alternation and inhibitory avoidance training.…”

“…Bélanger et al, 2011; Magistretti, 2006; Pellerin et al, 2007; Gibbs et al, 2008; Pirttimaki and Parri, 2013; Bezzi and Volterra, 2011; Gold and Korol, 2012; Gold et al, 2013). These findings support a sequence by which glucose is taken into astrocytes for production of glycogen stores, with glycogenolysis and production of lactate initiated during learning by activation of neurotransmitter membrane receptors on astrocytes.…”