Glucose injections into the dorsal hippocampus or dorsolateral striatum of rats prior to T-maze training: Modulation of learning rates and strategy selection

Abstract

The present experiments examined the effects of injecting glucose into the dorsal hippocampus or dorsolateral striatum on learning rates and on strategy selection in rats trained on a T-maze that can be solved by using either a hippocampus-sensitive place or striatum-sensitive response strategy. Percentage strategy selection on a probe trial (P crit ) administered after rats achieved criterion (nine of 10 correct choices) varied by group. All groups predominately exhibited a response strategy on a probe trial administered after overtraining, i.e., after 90 trials. In experiment 1, rats that received intrahippocampal glucose injections showed enhanced acquisition of the T-maze and showed increased use of response solutions at P crit compared with that of unimplanted and artificial cerebral spinal fluid (aCSF)-treated groups. These findings suggest that glucose enhanced hippocampal functions to accelerate the rate of learning and the early adoption of a response strategy. In experiment 2, rats that received intrastriatal glucose injections exhibited place solutions early in training and reached criterion more slowly than did aCSF controls, with learning rates comparable to those of unoperated and operated-uninjected controls. Relative to unoperated, operated-uninjected and glucose-injected rats, rats that received intrastriatal aCSF injections showed enhanced acquisition of the T-maze and increased use of response solutions at P crit . The unexpected enhanced acquisition seen after striatal aCSF injections suggests at least two possible interpretations: (1) aCSF impaired striatal function, thereby releasing competition with the hippocampus and ceding control over learning to the hippocampus during early training trials; and (2) aCSF enhanced striatal functioning to facilitate striatal-sensitive learning. With either interpretation, the results indicate that intrastriatal glucose injections compensated for the aCSF-induced effect. Finally, enhanced acquisition regardless of treatment was accompanied by rapid adoption of a response solution for the T-maze.Glucose is a potent modulator of learning and memory for many tasks in both humans and rodents (Gold 1995(Gold , 2001 Korol and Gold 1998). For example, systemic administration of glucose enhances memory for verbal tasks in humans (cf. Gold 2001; Korol 2002;Benton et al. 2003;Messier 2004;Watson and Craft 2004) and enhances learning and memory in rats and mice for appetitive, aversive, operant, visual discrimination, spatial working memory, habituation, and extinction tasks (cf. Messier andWhite 1984, 1987; Gold 1986Gold , 1995Messier and Destrade 1988; Kopf and Baratti 1996;Messier 1997;Pavone et al. 1998;Ragozzino et al. 1998;Sansone et al. 2000;Talley et al. 2000;Benton et al. 2003; Hughes 2003;Schroeder and Packard 2003).In addition to the effects seen with systemic injections, glucose can also enhance learning and memory when injected directly into specific brain regions. Glucose injections into the medial septum or hippocampus modulate memory of spontaneou...

Spatial Memory Formation and Memory-Enhancing Effect of Glucose Involves Activation of the Tuberous Sclerosis Complex–Mammalian Target of Rapamycin Pathway

“…Although systemic administration of glucose has been suggested to modulate memory via this peripheral mechanism, it has been shown that extracellular hippocampal glucose concentration decreases in rats when they perform a spatial navigation task, suggesting a central mechanism of action for glucose (McNay et al, 2000). Consistent with this suggestion, a few studies have indicated that direct injection of glucose into specific brain structures (e.g., amygdala or the hippocampus) can facilitate memory (Ragozzino and Gold, 1994;Ragozzino et al, 1998;Schroeder and Packard, 2003;Canal et al, 2005;Krebs and Parent, 2005). It is thought that centrally applied glucose may facilitate memory formation by restoring cellular energy levels that were reduced as a result of learning and/or by increasing the release of acetylcholine.…”

“…In addition, it has been demonstrated that age-related memory impairments in rodents can be reversed by injection of glucose near the time of training (Messier and Destrade, 1988;McNay and Gold, 2001). Although it is thought that the memory-enhancing effect of systemic glucose administration is mediated by peripheral release of epinephrine, this mechanism is not consistent with memory enhance-ment that is seen after intrahippocampal or intra-amygdalal glucose infusion (Ragozzino and Gold, 1994;Li et al, 1998;Ragozzino et al, 1998;Schroeder and Packard, 2003;Canal et al, 2005;Krebs and Parent, 2005).…”

Path planning versus cue responding: a bio-inspired model of switching between navigation strategies

“…Competition between two memory systems (and hence, the corresponding strategies) is demonstrated when a lesion of one of the systems entails an improvement of the learning of the other, while cooperation implies that such a lesion leads to the impairment of the other system's performance (Kim and Baxter 2001;Gold 2004). In the spatial domain, competition or cooperation between navigational strategies are respectively observed when one of the strategies perturbs (Packard and McGaugh 1992;Pearce et al 1998;Chang and Gold 2003;Canal et al 2005) or facilitates (McDonald and White 1994;Hamilton et al 2004;Voermans et al 2004) the other one for reaching the goal. The analysis of switching between place-and response-based strategies suggests that they can interact both across and within experimental trials (Pearce et al 1998;.…”

Re-thinking the role of the dorsal striatum in egocentric/response strategy

“…Pre-training lDS injections of artifi cial cerebral spinal fl uid (Canal et al, 2005), and post-training injections of glutamate into the lDS (presumed to induce striatal activation; Packard, 1999) have been shown to increase the use of the response strategy in very similar procedures. Such an effect could thus be interpreted as resulting from a lDS dysfunction due to intra striatal injections.…”

“…A large number of studies have shown that the use of place and response strategies early in training depends largely on intra-and extra-maze cue arrangements and densities (Tolman et al, 1946(Tolman et al, , 1947Restle, 1957;Oliveira et al, 1997;Passino et al, 2002;Canal et al, 2005). The capacity to use environmental cues to drive the behaviour (i.e.…”