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Learning-Induced Gene Expression in the Hippocampus Reveals a Role of Neuron -Astrocyte Metabolic Coupling in Long Term Memory.

Tadi M, Allaman I, Lengacher S, Grenningloh G, Magistretti PJ - PLoS ONE (2015)

Bottom Line: The quantitative determination of mRNA levels revealed learning-induced changes in the expression of genes thought to be involved in astrocyte-neuron metabolic coupling in a time dependent manner.Twenty four hours following IA training, an enhanced gene expression was seen, particularly for genes encoding monocarboxylate transporters 1 and 4 (MCT1, MCT4), alpha2 subunit of the Na/K-ATPase and glucose transporter type 1.Together, these observations indicate that neuron-glia metabolic coupling undergoes metabolic adaptations following learning as indicated by the change in expression of key metabolic genes.

View Article: PubMed Central - PubMed

Affiliation: Brain Mind Institute, Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland.

ABSTRACT
We examined the expression of genes related to brain energy metabolism and particularly those encoding glia (astrocyte)-specific functions in the dorsal hippocampus subsequent to learning. Context-dependent avoidance behavior was tested in mice using the step-through Inhibitory Avoidance (IA) paradigm. Animals were sacrificed 3, 9, 24, or 72 hours after training or 3 hours after retention testing. The quantitative determination of mRNA levels revealed learning-induced changes in the expression of genes thought to be involved in astrocyte-neuron metabolic coupling in a time dependent manner. Twenty four hours following IA training, an enhanced gene expression was seen, particularly for genes encoding monocarboxylate transporters 1 and 4 (MCT1, MCT4), alpha2 subunit of the Na/K-ATPase and glucose transporter type 1. To assess the functional role for one of these genes in learning, we studied MCT1 deficient mice and found that they exhibit impaired memory in the inhibitory avoidance task. Together, these observations indicate that neuron-glia metabolic coupling undergoes metabolic adaptations following learning as indicated by the change in expression of key metabolic genes.

No MeSH data available.


Related in: MedlinePlus

IA training results in enhanced and prolonged expression of ANLS related genes.Dorsal hippocampal tissue was collected 24 hours following inhibitory avoidance training (A) or 72 hours following inhibitory avoidance testing (B) and mRNA expression levels for the ANLS related genes were assessed by quantitative Q-PCR. Results are expressed as percentage of control values (CS group) and are means ± SEM. Data were statistically analyzed using two-tailed Student’s t test, * P < 0.05, ** P < 0.01, *** P < 0.001 vs CS group, n = 8/group for condition A and 7/group for condition B.
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pone.0141568.g002: IA training results in enhanced and prolonged expression of ANLS related genes.Dorsal hippocampal tissue was collected 24 hours following inhibitory avoidance training (A) or 72 hours following inhibitory avoidance testing (B) and mRNA expression levels for the ANLS related genes were assessed by quantitative Q-PCR. Results are expressed as percentage of control values (CS group) and are means ± SEM. Data were statistically analyzed using two-tailed Student’s t test, * P < 0.05, ** P < 0.01, *** P < 0.001 vs CS group, n = 8/group for condition A and 7/group for condition B.

Mentions: Transfer of energy substrates from astrocytes to neurons is the central point of the ANLS [5]. According to the ANLS, lactate produced preferentially by the astrocytes, is shuttled via specific monocarboxylate transporters (MCTs) from the astrocytes to the active neurons. Previous work has shown that lactate transport from astrocytes into neurons is necessary for long term memory formation [13] as well as for short term spatial working memory [14]. When examining ANLS related genes, no gene expression changes were seen 3 and 9 hours post IA training (data not shown). However, we found a late phase (24 hours following training) of enhanced dorsal hippocampal expression of several ANLS related genes in the CS-US group (Fig 2A, vs CS group, P < 0.05 for each unpaired t-test, n = 8). Specifically we observed a 46 ± 5.4% increase in mean mRNA levels of monocarboxylate transporter 1 (MCT1), 44 ± 8.3% increase in astrocytic monocarboxylate transporter 4 (MCT4), a 32 ± 6.4% increase in astrocytic glucose transporter 1 (Glut1), and a 20 ± 3.4% increase in Na/K-ATPase alpha2 subunit (Na/K alpha2). Note that a 23 ± 2.3% increase in neuronal glucose transporter 3 (Glut3) was also observed, while the neuronal Na/K alpha3 subunit expression remained unaltered (data not shown). In contrast to the dorsal hippocampal gene expression results, no induction of ANLS related genes was observed in the somatosensory cortex of the CS-US group, 24 hours after IA training (S1 Table). Furthermore, to investigate if shock alone had any effect on the expression/modulation of genes related to brain energy metabolism following IA task, a US group (shock only) was included to the experimental paradigm. Mice in the US group were directly placed in the dark compartment where they received a foot shock and were immediately removed from the box after the foot shock to block context-shock association [38–40]. When compared to the CS group, there was no induction of ANLS related genes in the US group, 24 hours after IA training (S2 Table).


Learning-Induced Gene Expression in the Hippocampus Reveals a Role of Neuron -Astrocyte Metabolic Coupling in Long Term Memory.

Tadi M, Allaman I, Lengacher S, Grenningloh G, Magistretti PJ - PLoS ONE (2015)

IA training results in enhanced and prolonged expression of ANLS related genes.Dorsal hippocampal tissue was collected 24 hours following inhibitory avoidance training (A) or 72 hours following inhibitory avoidance testing (B) and mRNA expression levels for the ANLS related genes were assessed by quantitative Q-PCR. Results are expressed as percentage of control values (CS group) and are means ± SEM. Data were statistically analyzed using two-tailed Student’s t test, * P < 0.05, ** P < 0.01, *** P < 0.001 vs CS group, n = 8/group for condition A and 7/group for condition B.
© Copyright Policy
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4625956&req=5

pone.0141568.g002: IA training results in enhanced and prolonged expression of ANLS related genes.Dorsal hippocampal tissue was collected 24 hours following inhibitory avoidance training (A) or 72 hours following inhibitory avoidance testing (B) and mRNA expression levels for the ANLS related genes were assessed by quantitative Q-PCR. Results are expressed as percentage of control values (CS group) and are means ± SEM. Data were statistically analyzed using two-tailed Student’s t test, * P < 0.05, ** P < 0.01, *** P < 0.001 vs CS group, n = 8/group for condition A and 7/group for condition B.
Mentions: Transfer of energy substrates from astrocytes to neurons is the central point of the ANLS [5]. According to the ANLS, lactate produced preferentially by the astrocytes, is shuttled via specific monocarboxylate transporters (MCTs) from the astrocytes to the active neurons. Previous work has shown that lactate transport from astrocytes into neurons is necessary for long term memory formation [13] as well as for short term spatial working memory [14]. When examining ANLS related genes, no gene expression changes were seen 3 and 9 hours post IA training (data not shown). However, we found a late phase (24 hours following training) of enhanced dorsal hippocampal expression of several ANLS related genes in the CS-US group (Fig 2A, vs CS group, P < 0.05 for each unpaired t-test, n = 8). Specifically we observed a 46 ± 5.4% increase in mean mRNA levels of monocarboxylate transporter 1 (MCT1), 44 ± 8.3% increase in astrocytic monocarboxylate transporter 4 (MCT4), a 32 ± 6.4% increase in astrocytic glucose transporter 1 (Glut1), and a 20 ± 3.4% increase in Na/K-ATPase alpha2 subunit (Na/K alpha2). Note that a 23 ± 2.3% increase in neuronal glucose transporter 3 (Glut3) was also observed, while the neuronal Na/K alpha3 subunit expression remained unaltered (data not shown). In contrast to the dorsal hippocampal gene expression results, no induction of ANLS related genes was observed in the somatosensory cortex of the CS-US group, 24 hours after IA training (S1 Table). Furthermore, to investigate if shock alone had any effect on the expression/modulation of genes related to brain energy metabolism following IA task, a US group (shock only) was included to the experimental paradigm. Mice in the US group were directly placed in the dark compartment where they received a foot shock and were immediately removed from the box after the foot shock to block context-shock association [38–40]. When compared to the CS group, there was no induction of ANLS related genes in the US group, 24 hours after IA training (S2 Table).

Bottom Line: The quantitative determination of mRNA levels revealed learning-induced changes in the expression of genes thought to be involved in astrocyte-neuron metabolic coupling in a time dependent manner.Twenty four hours following IA training, an enhanced gene expression was seen, particularly for genes encoding monocarboxylate transporters 1 and 4 (MCT1, MCT4), alpha2 subunit of the Na/K-ATPase and glucose transporter type 1.Together, these observations indicate that neuron-glia metabolic coupling undergoes metabolic adaptations following learning as indicated by the change in expression of key metabolic genes.

View Article: PubMed Central - PubMed

Affiliation: Brain Mind Institute, Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland.

ABSTRACT
We examined the expression of genes related to brain energy metabolism and particularly those encoding glia (astrocyte)-specific functions in the dorsal hippocampus subsequent to learning. Context-dependent avoidance behavior was tested in mice using the step-through Inhibitory Avoidance (IA) paradigm. Animals were sacrificed 3, 9, 24, or 72 hours after training or 3 hours after retention testing. The quantitative determination of mRNA levels revealed learning-induced changes in the expression of genes thought to be involved in astrocyte-neuron metabolic coupling in a time dependent manner. Twenty four hours following IA training, an enhanced gene expression was seen, particularly for genes encoding monocarboxylate transporters 1 and 4 (MCT1, MCT4), alpha2 subunit of the Na/K-ATPase and glucose transporter type 1. To assess the functional role for one of these genes in learning, we studied MCT1 deficient mice and found that they exhibit impaired memory in the inhibitory avoidance task. Together, these observations indicate that neuron-glia metabolic coupling undergoes metabolic adaptations following learning as indicated by the change in expression of key metabolic genes.

No MeSH data available.


Related in: MedlinePlus