Importance of glutamate‐generating metabolic pathways for memory consolidation in chicks

Abstract

Glutamatergic and noradrenergic stimulation is essential for formation of memory of single-trial discriminative avoidance of colored beads in the 1-day-old chick. Transmitter glutamate is released soon after training and again before memory consolidation 30 min after training. Memory consolidation is abolished by posttraining injection of iodoacetate, which inhibits glycolysis and thus not only energy metabolism but also pyruvate carboxylase-dependent glucose conversion to glutamate, needed for consolidation; a similar effect is evoked by the antagonists propranolol acting at beta(2)-adrenoceptors or SR59230A acting at beta(3)-adrenoceptors. This paper shows that the effect of these inhibitors can be overcome by central injection of glutamine, providing an alternate source of transmitter glutamate and compensating for the inhibition of glycolysis by iodoacetate or the blockade of adrenergic stimulation of glycogenolysis by propranolol or of glucose uptake by SR59230A. Conversely, inhibition of memory consolidation by methionine sulfoximine (MSO), an inhibitor of glutamine synthetase and thus of the glutamate-glutamine cycle, essential for neuronal reaccumulation of previously released transmitter glutamate, could be challenged by noradrenaline, stimulating glucose uptake and glycogenolysis and providing glutamate synthesis from glucose to compensate for the lack of return of previously released glutamate. Also, administration of either glutamine or noradrenaline could prevent the spontaneous decay of labile memory 30 min after training on a weakened stimulus, suggesting that direct supply of glutamate from glucose may secure sufficient supplies of transmitter glutamate for release prior to memory consolidation at 30 min.

Distribution of vesicular glutamate transporter 2 and glutamate receptor 1 mRNA in the central nervous system of the pigeon (Columba livia)

“…Passive avoidance tasks also induce an increase in AMPA and NMDA receptor binding in the intermediate medial mesopallium . Memory consolidation of single-trial discriminative avoidance of colored beads training is abolished by injection of iodoacatate (inhibits glycolysis to glutamate formation) into the intermediate mesopallium, but the inhibitor effect can be overcome with the injection of glutamine (an alternate source of glutamate) into the medial mesopallium within 25 minutes after training (Gibbs and Hertz, 2005). In the present study, glutamatergic neurons were detected in the hippocampus and mesopallium.…”

Astroglial Glutamate–Glutamine Shuttle Is Involved in Central Sensitization of Nociceptive Neurons in Rat Medullary Dorsal Horn

“…MSO has been widely used as a GS inhibitor in astroglia in studies of hyperammonemia, memory consolidation, and seizures, and its effects can be counteracted by glutamine application (Bacci et al, 2002;Suarez et al, 2002;Gibbs and Hertz, 2005;Tanigami et al, 2005;Liang et al, 2006). One recent study has used MSO to examine the effect of inflammatory stimuli on activation of GS in astroglia and found that GS activation is related to glutamatergic receptor activation (Muscoli et al, 2005).…”

“…This shuttle includes the uptake of excessive extrasynaptic glutamate and the production [via glutamine synthetase (GS)] and release from astroglia of glutamine, which is then taken up by neuronal elements to replenish the supply of glutamate (Zwingmann and Leibfritz, 2003;Hertz, 2004;Hertz and Zielke, 2004;Fonseca et al, 2005). A potent inhibitor of GS in astroglia is methionine sulfoximine (MSO), and its effects can be counteracted by glutamine application (Bacci et al, 2002;Blin et al, 2002;Suarez et al, 2002;Shin et al, 2003;Gibbs and Hertz, 2005;Tanigami et al, 2005;Liang et al, 2006). However, only one study has used MSO to investigate the involvement of astroglial GS in the effects of noxious stimuli on glutamatergic receptor-related events in astroglia (Muscoli et al, 2005), and no studies have tested its effects on central sensitization in functionally identified nociceptive neurons.…”

How Energy Metabolism Supports Cerebral Function: Insights from 13C Magnetic Resonance Studies In vivo

“…However, no change in brain glycogen level was measured during visual stimulation in humans (Oz et al, 2007). While glycogen-derived lactate has been demonstrated to have a pivotal role in memory formation and consolidation (Gibbs and Hertz, 2005; Suzuki et al, 2011; Boury-Jamot et al, 2016), learning mechanism and synaptic strength (Duran et al, 2013), and neuronal function (Tekkök et al, 2005), the role of glycogen is unlikely limited to fuel neuronal metabolism. Recently, astrocytic glycogenolysis was shown to provide energy to sustain glutamatergic neurotransmission (i.e., glutamate uptake and release; Sickmann et al, 2009).…”