**2. Memory as an integral function of neurons**

More than 90% of human activities are dependent on higher integrative brain functions – a major subdivision, which is the topic of our discussion in the chapter. The higher integrative brain functions are the driving force during physical work. This is because the brain is the "chief" that directs resources for the successful completion of the task. Successful

activities of humans are largely dependent on memory function [22]. This function of neurons becomes vividly indispensable in situations involving its disorder. Memory is that function of neurons that involve storage and retrieval of information [22]. Some research‐ ers have argued "forgetting" as an important aspect of memory function [23, 24]. This is partly because without forgetting, some new information might hardly go into storage. Hence, there are theories of forgetting – the most known ones are the single-trace fragili‐ ty theory, decay theory, retrieval failure, interference theory, repression, consolidation theory [22]. Generally, several concepts/theories/models/hypotheses have been used to explain memory function of neurons [22, 25-27]. However, with steady scientific progress it is becoming clearer that none of these gives a complete, and precise definition of memory. In this regard, we shall also discuss briefly on the modern concepts of memory function of neurons in relation to cerebral glucose metabolism.

Modulating factors of the glucose memory facilitation effect include physiological state (body mass index etc.), glucose dose, types of cognitive tasks used and cognitive demand [9, 39]. These factors are the possible sources of variance in the glucose facilitation of memory. Owen and colleagues (2008) investigated the dose response relationship of the glucose memory facilitation effect at glucose dosages of 0, 15, 25, 50 and 60 g [9]. They also examined the interactions between length of fasting interval (2 hours versus 12 hours) and the optimum dose of glucose. Their results revealed glucose facilitation of spatial working memory and verbal declarative memory following 25 g glucose. Furthermore, they observed that glucose memory facilitation effect is dependent on the following: the greater the length of fasting, the greater the glucose dose needed to facilitate memory [9]. So, at overnight fast (approximately 12 hours) the higher dose of glucose (i.e. 60 g) was needed to facilitate memory, whereas the lower dose

glucose (i.e. 60 g) was needed to facilitate memory, whereas the lower dose (25 g) enhanced

Exogenous, endogenous Ethanol

Set point (~4.5 mmol/l) of glycemia

Brain (Hypothalamus)

> Cerebral glucose

> > ?

Synthesis & activity of neurotransmitter systems (dopamine, d-serine, glutamate, Ach etc.)

LTP/LTD

Genetic and epigenetic modifications

Metabolic signaling pathways

Synthesis & activity of receptor subunits

**Memory** 

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The mechanisms responsible for memory formation and retrieval are in constant perturbations of several factors (which might be competing factors, endogenous or exogenous in nature). The processes and mechanisms that ensure memory formation are the synthesis and activity of neurotransmitters (dopamine, d-serine, glutamate, acetylcholine etc), and receptor subunit systems; metabolic signaling pathways; LTP/LTD (long-term potentiation/long-term depression); genetic and epigenetic modifications. (Memory retrieval might involve the same systems and processes, but with different mechanisms). Both memory formation and retrieval involve other brain functions, including attention. The systems and processes earlier stated are affected by cerebral glucose, which can serve as a substrate or produce intermediate substrates for some stages of their syntheses. The cerebral glucose content is dependent on the plasma glucose, both of which are under constant regulation by the brain (hypothalamus), some internal organs (liver, kidney). The blood glucose is constantly regulated, also by the effect of the neuroendocrine control on the gastrointestinal tract, organs (such as the liver and kidney), as well as the effect of the hypothalamus on these organs. The processes that are regulated in these organs

The mechanisms responsible for memory formation and retrieval are in constant perturba‐ tions of several factors (which might be competing factors, endogenous or exogenous in nature). The processes and mechanisms that ensure memory formation are the synthesis and activity of neurotransmitters (dopamine, d-serine, glutamate, acetylcholine etc), and

(25 g) enhanced working memory performance following a 2 hour fast [9].

working memory performance following a 2 hour fast [9].

Processes: Gluconeogenesis, glucogenolysis

Figure 1. Comprehensive model of glucose memory facilitation

**Figure 1.** Comprehensive model of glucose memory facilitation

Plasma glucose

Liver, kidney

Gastrointestinal tract

Neuro-endocrine control

Carbohydrate containing food

Self-regulatory mechanisms (glucose cycling)
