poster template v1

Hippocampal Extracellular Lactate Increases During Learning:
A Role for Astrocytes in Learning and Memory
Paul E.
1,2,3,4
Gold
,
Claire J.
1
Scavuzzo ,
1,2,4
Korol ,
Donna L.
Lori A.
823.14
1,2
Newman
1Neuroscience
Program, 2Department of Psychology,
3Department of Psychiatry, 4Departments of Integrative and Molecular Biology, Bioengineering, Institute for Genomic Biology, University of Illinois at Urbana and Champaign, Champaign, IL
Introduction
NEURON
CAPILLARY
MCT-2
G-6-P
LACTATE
LACTATE
MCT-1
PYRUVATE
Figure 1. The astrocyte-neuron
lactate shuttle
During memory formation,
astrocytes produce lactate via
glycolysis and glycogenolysis.
The lactate is then preferentially
used as an energy source by
neurons (from Newman et al.,
PLoS ONE, 2011).
GLYCOGEN
TCA
In this experiment, a biosensor probe detecting lactate or glucose was inserted
in the hippocampus or striatum of young Sprague-Dawley male rats to determine
changes in the extracellular concentrations of these substrates during training on
hippocampus-selective place or striatum-selective response learning tasks. If
lactate and/or glucose are linked to memory formation they should be
differentially altered in the hippocampus and striatum across cognitive tasks.
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Cheerio
Response
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Conclusions
Striatal Lactate During Place and
Response Learning
Lactate (Change in µM from Baseline)
G-6-P
Hippocampal Lactate During Place
and Response Learning
Lactate (Change in µM from Baseline)
ASTROCYTE
GLUCOSE
Results
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Cheerio
Response
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Place
Place
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Method
Surgery
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Average Correct Trial Ratio
Average Correct Trial Ratio
Hippocampal Glucose During Place
and Response Learning
Striatal Glucose During Place and
Response Learning
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• Rats trained in the place task had higher increases in extracellular lactate and
glucose in the hippocampus than did rats in the response task or untrained
rats fed Cheerios.
• During place training, the increases in lactate in the hippocampus are
likely due to increases in astrocytic glycogenolysis and glycolysis,
suggesting that astrocytes in the hippocampus respond specifically to
task demands.
• During place training, increases in glucose are likely due to preferentially
increased glucose uptake from the periphery into the hippocampus.
• These findings are in contrast to previous findings of
decreased glucose during spontaneous alternation testing.
This is likely due to an altered energy status, as the current
study used food restricted rats and cheerio ingestion during
the task.
• Increases in hippocampal lactate and glucose from baseline in the
response-trained and Cheerios-eating groups are likely due to Cheerios
ingestion and subsequent increases in blood glucose levels.
• Rats in the place task had lower extracellular lactate in the striatum upon task
acquisition, compared to rats in the response task or Cheerios eating naïve
group.
• Decreases in extracellular lactate in the place-trained group are likely due
to decreases in astrocytic glycogenolysis and glycolysis, suggesting that
astrocytes in the striatum are quiescent during hippocampal sensitive
tasks.
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Behavioral Testing
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Response
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Figure 4. Rat with biosensor in response maze
Place Learning
Response Learning
Cheerios
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Average Correct Trial Ratio
Trial by trial analyses will be
conducted to determine if there
are any differences in lactate
and glucose during correct vs.
incorrect trials.
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BLOOD GLUCOSE OF FOOD
RESTRICTED RATS (80-85%)
Figure 6. Response Training
A striatum-selective learning task in which a rat
uses egocentric body movements to retrieve a
food reward by always turning in the same
direction. This task was performed in a in a
cue-poor environment.
Untrained controls were fed 1/3 of a Cheerio® every 1.5 minutes for 52.5 minutes while in
their home cages.
All animals were food-restricted to 80-85% of their baseline body weight prior to testing.
BLOOD GLUCOSE (mg/dL)
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Figure 5. Place Training
A hippocampus-selective learning task in which
a rat uses extramaze cues to retrieve a food
reward in the same location.
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Correct Place
Incorrect Place
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Arm Choice
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Time From Arm Choice (Seconds)
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We plan to conduct similar experiments using water reinforcement to avoid the
possibility of the task associated changes in brain glucose levels due to
Cheerios causing changes in blood glucose levels.
Average Correct Trial Ratio
There was a significant rise in both lactate and glucose during all tasks in both the
hippocampus and the striatum. Additionally glucose and lactate increased
significantly more during place training in the hippocampus. Overall, greater
increases in lactate were seen in the hippocampus than in the striatum.
A significant rise in blood glucose
is also seen during cheerio
feeding which could be
contributing significantly to the
rise in glucose in the brain.
Extracellular Lactate Around Arm Choice
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Lactate Change (µM)
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Glucose (Change in µM from Baseline)
Figure 2. Biosensor cannula placement
A biosensor was inserted in the dorsal hippocampus
(as above) or striatum (not shown) for measurement
of extracellular lactate or glucose.
Figure 3. Biosensor structure
The biosensor contains a layer of oxidase enzymes, able
to breakdown lactate or glucose. The detection of these
molecules is signalled via electron transfer to a platinum
wire in the probe.
Glucose (Change in µM from Baseline)
Future Directions
Acknowledgments
Postdoctoral Support: NIH Training Grant HD007333
Research Support: NIH grants AG07648 and DA024129, NSF grants IOS 1052464 and 08-43175 and an award from the Alzheimer’s Association.
Special thanks to Elizabeth Rivera-Cruz, Laura Manning, Joseph Song, Sunjay
Koshy, Sydney Muchnik, Heather Lin, and Fiona Weingartner for their valuable
participation on this project.
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References
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Time from Start of Cheerio Feeding (Min)
•Magistretti PJ. 2006. Neuron-glia metabolic coupling and plasticity. Journal of
Experimental Biology 209(12):2304-2311.
•Chuquet J, Quilichini P, Nimchinsky EA, Buzsáki G. 2010. Predominant
enhancement of glucose uptake in astrocytes versus neurons during activation
of the somatosensory cortex. Journal of Neuroscience 30(45):15298-15303.
•Newman, LA, Korol, DL, Gold, PE. 2011. Lactate produced by glycogenolysis in
astrocytes regulates memory processing. PLoS ONE, in press.