Modulation of Hippocampal Acetylcholine Release and Spontaneous Alternation Scores by Intrahippocampal Glucose Injections

Abstract

Recent evidence indicates that systemic glucose treatment enhances memory while producing a corresponding increase in hippocampal acetylcholine (ACh) output. The present experiments examined whether unilateral intrahippocampal infusions of glucose would enhance spontaneous alternation performance and whether there would be a corresponding increase in ACh output in the ipsilateral and contralateral hippocampus. Extracellular ACh was assessed in samples collected at 12 min intervals using in vivo microdialysis with HPLC with electrochemical detection. Twelve minutes after a unilateral infusion of artificial cerebrospinal fluid (CSF) or glucose (6.6 mM), rats were tested in a cross maze for spontaneous alternation behavior with concurrent microdialysis collection. In two experiments, glucose infusions significantly increased alternation scores (67.5 and 59%) compared with CSF controls (42.4 and 39.5%, respectively). In both experiments, behavioral testing resulted in increased ACh output in the hippocampus. Glucose administration at the time of alternation tests enhanced ACh output beyond that of behavioral testing alone both ipsilateral (+93.8%) and contralateral (+85%) to the infusion site, as compared with ACh output (+36.1% and +55.5%) of CSF controls. Glucose infusions did not affect hippocampal ACh output in rats kept in a holding chamber. These results suggest that glucose may enhance alternation scores by modulating ACh release. The findings also indicate that unilateral glucose infusions increase hippocampal ACh output both ipsilateral and contralateral to the site of injection. Furthermore, glucose increased ACh output only during maze testing, suggesting that specific behavioral demands, perhaps requiring activation of cholinergic neurons, determine the efficacy of glucose in modulating ACh release.

Age-related changes in memory and in acetylcholine functions in the hippocampus in the Ts65Dn mouse, a model of Down syndrome

“…Spontaneous alternation tasks as used in present study have previously been found to elicit ACh release in the hippocampus of rats in a manner related to memory performance on this task (Chang and Gold, 2004;Ragozzino and Gold, 1995;Ragozzino et al, 1996Ragozzino et al, , 1998Pych et al, 2005). The microdialysis results presented here suggest that the onset of dysfunctions in septohippocampal cholinergic functions, i.e.…”

“…The maze had four identical arms (25.5 x 7.7 x 10.0 cm, L x W x H) extending from a central platform (7.7 x 7.7 cm). Mice were allowed to traverse the maze freely as in previous studies with rats (Chang and Gold, 2004;McNay and Gold, 2001;Ragozzino et al, 1996Ragozzino et al, , 1998Pych et al, 2005;Gold, 1998, 2001). After being placed in the central platform, mice were permitted to move freely through the maze for 6 minutes.…”

“…Third, there is clear association in rats of spontaneous alternation scores and release of ACh in the hippocampus. Release of ACh in the hippocampus increases during exploratory behavior (Giovannini et al, 2001) and alternation testing; during spontaneous alternation testing, the magnitude of release is related to alternation scores under many conditions (Ragozzino, Unick and Gold, 1996;Ragozzino et al, 1998;Pych et al, 2005). Fourth, as a test of working memory, each mouse can be tested on multiple occasions under different conditions permitting use of fewer mice.…”

Glucose enhancement of human memory: A comprehensive research review of the glucose memory facilitation effect

“…Therefore, on the basis of these results, it appears that glucose administration may facilitate memory by directly increasing hippocampal ACh synthesis in a dose dependent manner. These results were subsequently extended, in that injecting glucose into the hippocampus unilaterally was observed to increase ACh output from both the ipsilateral and contralateral hippocampus (Ragozzino et al, 1998).…”

Role of β-Adrenoceptors in Memory Consolidation: β3-Adrenoceptors Act on Glucose Uptake and β2-Adrenoceptors on Glycogenolysis

“…We have also found this multimodal brain region to be important in the formation of memory in both passive avoidance and bead discrimination learning paradigms (Gibbs and Ng, 1977;Gibbs and Summers, 2002a). Memory formation is energy dependent and central injection of glucose can modulate memory (Ragozzini et al, 1998;Krebs and Parent, 2005;McNay et al, 2000McNay et al, , 2001. Memory formation can be inhibited by 2-deoxyglucose (DG; Gibbs and Summers, 2002b), which is not metabolized and by DAB (1,4-dideoxy-1,4-imino-D-arabinitol) an inhibitor of glycogen breakdown (Gibbs et al 2006a).…”