TY - JOUR
T1 - Second-by-second measures of L-glutamate in the prefrontal cortex and striatum of freely moving mice
AU - Hascup, E. R.
AU - Pomerleau, F.
AU - Huettl, P.
AU - Gerhardt, G. A.
AU - Hascup, Kevin N.
PY - 2008/2
Y1 - 2008/2
N2 - L-Glutamate (Glu) is the main excitatory neurotransmitter in the mammalian central nervous system, and it is involved in most aspects of normal brain function, including cognition, memory and learning, plasticity, and motor movement. Although microdialysis techniques have been used to study Glu, the slow temporal resolution of the technique may be inadequate to properly examine tonic and phasic Glu. Thus, our laboratory has developed an enzyme-based microelectrode array (MEA) with fast response time and low detection limits for Glu. We have modified the MEA design to allow for reliable measures in the brain of awake, freely moving mice. In this study, we chronically implanted the MEA in prefrontal cortex (PFC) or striatum (Str) of awake, freely moving C57BL/6 mice. We successfully measured Glu levels 7 days postimplantation without loss of MEA sensitivity. In addition, we determined resting (tonic) Glu levels to be 3.3 μM in the PFC and 5.0 μM in the Str. Resting Glu levels were subjected to pharmacological manipulation with tetrodotoxin (TTX) and DL-threo-β-hydroxyaspartate (THA). TTX significantly (p < 0.05) decreased resting Glu by 20%, whereas THA significantly (p < 0.05) increased resting Glu by 60%. Taken together, our data show that chronic recordings of tonic and phasic clearance of exogenously applied Glu can be carried out in awake mice for at least 7 days in vivo, allowing for longer term studies of Glu regulation.
AB - L-Glutamate (Glu) is the main excitatory neurotransmitter in the mammalian central nervous system, and it is involved in most aspects of normal brain function, including cognition, memory and learning, plasticity, and motor movement. Although microdialysis techniques have been used to study Glu, the slow temporal resolution of the technique may be inadequate to properly examine tonic and phasic Glu. Thus, our laboratory has developed an enzyme-based microelectrode array (MEA) with fast response time and low detection limits for Glu. We have modified the MEA design to allow for reliable measures in the brain of awake, freely moving mice. In this study, we chronically implanted the MEA in prefrontal cortex (PFC) or striatum (Str) of awake, freely moving C57BL/6 mice. We successfully measured Glu levels 7 days postimplantation without loss of MEA sensitivity. In addition, we determined resting (tonic) Glu levels to be 3.3 μM in the PFC and 5.0 μM in the Str. Resting Glu levels were subjected to pharmacological manipulation with tetrodotoxin (TTX) and DL-threo-β-hydroxyaspartate (THA). TTX significantly (p < 0.05) decreased resting Glu by 20%, whereas THA significantly (p < 0.05) increased resting Glu by 60%. Taken together, our data show that chronic recordings of tonic and phasic clearance of exogenously applied Glu can be carried out in awake mice for at least 7 days in vivo, allowing for longer term studies of Glu regulation.
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U2 - 10.1124/jpet.107.131698
DO - 10.1124/jpet.107.131698
M3 - Article
C2 - 18024788
AN - SCOPUS:38749117858
SN - 0022-3565
VL - 324
SP - 725
EP - 731
JO - Journal of Pharmacology and Experimental Therapeutics
JF - Journal of Pharmacology and Experimental Therapeutics
IS - 2
ER -