Astrocyte-Neuron Lactate Transport Is Required for Long-Term Memory Formation

Suzuki, Akinobu; Stern, Sarah A.; Bozdagi, Ozlem; Huntley, George W.; Walker, Ruth H.; Magistretti, Pierre J.; Alberini, Cristina M.

doi:10.1016/j.cell.2011.02.018

Cited by 1,352 publications

(1,543 citation statements)

References 61 publications

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“…Since bioenergetics are tightly coupled to cognitive function, abnormal metabolism in the prefrontal cortex may directly impact cognitive tasks such as working memory in schizophrenia (60-62). There remain significant challenges in developing high efficacy therapeutics for schizophrenia, but substrates modulating bioenergetic systems such as glycolysis and oxidative phosphorylation could offer plausible avenues for development of novel pharmacological interventions.…”

Section: Discussionmentioning

confidence: 99%

Neuron-specific deficits of bioenergetic processes in the dorsolateral prefrontal cortex in schizophrenia

et al. 2018

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Schizophrenia is a devastating illness that affects over 2 million people in the U.S. and costs society billions of dollars annually. New insights into the pathophysiology of schizophrenia are needed to provide the conceptual framework to facilitate development of new treatment strategies. We examined bioenergetic pathways in the dorsolateral prefrontal cortex (DLPFC) of subjects with schizophrenia and control subjects using western blot analysis, quantitative real-time polymerase chain reaction, and enzyme/substrate assays. Laser-capture microdissection-qPCR was used to examine these pathways at the cellular level. We found decreases in hexokinase (HXK) and phosphofructokinase (PFK) activity in the DLPFC, as well as decreased PFK1 mRNA expression. In pyramidal neurons, we found an increase in monocarboxylate transporter 1 mRNA expression, and decreases in HXK1, PFK1, glucose transporter 1 (GLUT1), and GLUT3 mRNA expression. These results suggest abnormal bioenergetic function, as well as a neuron-specific defect in glucose utilization, in the DLPFC in schizophrenia.

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Section: Discussionmentioning

confidence: 99%

Neuron-specific deficits of bioenergetic processes in the dorsolateral prefrontal cortex in schizophrenia

et al. 2018

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“…Altered glial coverage could also affect astrocyte‐neuron lactate transport contributing to synaptic efficacy (Suzuki et al, 2011) and local water homeostasis (Simard and Nedergaard, 2004). In summary, there is a plethora of physiologically plausible candidate mechanisms that could underpin the adaptive role of astroglial remodeling in local neural network activity.…”

Section: Discussionmentioning

confidence: 99%

Morphological plasticity of astroglia: Understanding synaptic microenvironment

Heller

Rusakov

2015

Glia

132

137

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Memory formation in the brain is thought to rely on the remodeling of synaptic connections which eventually results in neural network rewiring. This remodeling is likely to involve ultrathin astroglial protrusions which often occur in the immediate vicinity of excitatory synapses. The phenomenology, cellular mechanisms, and causal relationships of such astroglial restructuring remain, however, poorly understood. This is in large part because monitoring and probing of the underpinning molecular machinery on the scale of nanoscopic astroglial compartments remains a challenge. Here we briefly summarize the current knowledge regarding the cellular organisation of astroglia in the synaptic microenvironment and discuss molecular mechanisms potentially involved in use‐dependent astroglial morphogenesis. We also discuss recent observations concerning morphological astroglial plasticity, the respective monitoring methods, and some of the newly emerging techniques that might help with conceptual advances in the area. GLIA 2015;63:2133–2151

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“…Accordingly, several reports have described the importance of glycogenolysis for memory processing. 11,12 To unequivocally approach the study of the role of glycogen in the brain, here we generated a mouse model that lacks Glycogen Synthase specifically in the nervous system (GYS1 Nestin-KO ). We analyzed the learning capacity of these animals and checked for differences in the electrophysiologic properties of the hippocampal CA3-CA1 synapse.…”

Section: Introductionmentioning

confidence: 99%

Impairment in Long-Term Memory Formation and Learning-Dependent Synaptic Plasticity in Mice Lacking Glycogen Synthase in the Brain

Durán

Sáez

Gruart

et al. 2013

J Cereb Blood Flow Metab

132

127

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Glycogen is the only carbohydrate reserve of the brain, but its overall contribution to brain functions remains unclear. Although it has traditionally been considered as an emergency energetic reservoir, increasing evidence points to a role of glycogen in the normal activity of the brain. To address this long-standing question, we generated a brain-specific Glycogen Synthase knockout (GYS1 Nestin-KO ) mouse and studied the functional consequences of the lack of glycogen in the brain under alert behaving conditions. These animals showed a significant deficiency in the acquisition of an associative learning task and in the concomitant activity-dependent changes in hippocampal synaptic strength. Long-term potentiation (LTP) evoked in the hippocampal CA3-CA1 synapse was also decreased in behaving GYS1 Nestin-KO mice. These results unequivocally show a key role of brain glycogen in the proper acquisition of new motor and cognitive abilities and in the underlying changes in synaptic strength.

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Astrocyte-Neuron Lactate Transport Is Required for Long-Term Memory Formation

Cited by 1,352 publications

References 61 publications

Neuron-specific deficits of bioenergetic processes in the dorsolateral prefrontal cortex in schizophrenia

Neuron-specific deficits of bioenergetic processes in the dorsolateral prefrontal cortex in schizophrenia

Morphological plasticity of astroglia: Understanding synaptic microenvironment

Impairment in Long-Term Memory Formation and Learning-Dependent Synaptic Plasticity in Mice Lacking Glycogen Synthase in the Brain

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