Glutamatergic and dopaminergic afferents to the prefrontal cortex regulate spatial working memory in rats
The integrity of the prefrontal cortex is critical for the expression of working memory. The prefrontal cortex is innervated by dopaminergic afferents from the ventral tegmental area and glutamatergic afferents from the mediodorsal thalamus. To determine the role of dopaminergic and glutamatergic af...
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Published in | Neuroscience Vol. 92; no. 1; pp. 97 - 106 |
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Main Authors | , , |
Format | Journal Article |
Language | English |
Published |
Oxford
Elsevier Ltd
01.01.1999
Elsevier |
Subjects | |
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Abstract | The integrity of the prefrontal cortex is critical for the expression of working memory. The prefrontal cortex is innervated by dopaminergic afferents from the ventral tegmental area and glutamatergic afferents from the mediodorsal thalamus. To determine the role of dopaminergic and glutamatergic afferents in the regulation of working memory, rats were trained to perform a spatial delayed alternation task in a T-maze. The microinjection of the ionotropic glutamate antagonists 6-cyano-7-nitroquinoxaline-2,3-dione or 3-(
R)-2-carboxypiperazin-4-propyl-1-phosphonic acid into the prefrontal cortex impaired working memory. Consistent with a role for glutamate receptor activation, microinjecting the GABA
B agonist baclofen into the mediodorsal thalamus produced a dose-dependent disruption of working memory. In contrast, inhibition of the mesocortical dopamine projection was without effect on working memory. The blockade of D
1 and/or D
2 dopamine receptors with SCH-23390 and sulpiride was without effect on working memory. Likewise, the microinjection of baclofen into the ventral tegmental area did not impair working memory. However, stimulating mu-opioid receptors in the ventral tegmental area with [
d-Ala
2,
N-Me-Phe
4,Gly-ol
5]enkephalin produced a dose-dependent impairment of working memory that was reversed by blocking D
1 dopamine receptors with SCH-23390 in the prefrontal cortex.
These data demonstrate that increased dopamine tone or reduced glutamate tone in the prefrontal cortex disrupts working memory in a spatial delayed alternation task. |
---|---|
AbstractList | The integrity of the prefrontal cortex is critical for the expression of working memory. The prefrontal cortex is innervated by dopaminergic afferents from the ventral tegmental area and glutamatergic afferents from the mediodorsal thalamus. To determine the role of dopaminergic and glutamatergic afferents in the regulation of working memory, rats were trained to perform a spatial delayed alternation task in a T-maze. The microinjection of the ionotropic glutamate antagonists 6-cyano-7-nitroquinoxaline-2,3-dione or 3-(R)-2-carboxypiperazin-4-propyl-1-phosphonic acid into the prefrontal cortex impaired working memory. Consistent with a role for glutamate receptor activation, microinjecting the GABA sub(B) agonist baclofen into the mediodorsal thalamus produced a dose-dependent disruption of working memory. In contrast, inhibition of the mesocortical dopamine projection was without effect on working memory. The blockade of D sub(1) and/or D sub(2) dopamine receptors with SCH-23390 and sulpiride was without effect on working memory. Likewise, the microinjection of baclofen into the ventral tegmental area did not impair working memory. However, stimulating mu-opioid receptors in the ventral tegmental area with [D-Ala super(2),N-Me-Phe super(4),Gly-ol super(5)]enkephalin produced a dose-dependent impairment of working memory that was reversed by blocking D sub(1) dopamine receptors with SCH-23390 in the prefrontal cortex. These data demonstrate that increased dopamine tone or reduced glutamate tone in the prefrontal cortex disrupts working memory in a spatial delayed alternation task. The integrity of the prefrontal cortex is critical for the expression of working memory. The prefrontal cortex is innervated by dopaminergic afferents from the ventral tegmental area and glutamatergic afferents from the mediodorsal thalamus. To determine the role of dopaminergic and glutamatergic afferents in the regulation of working memory, rats were trained to perform a spatial delayed alternation task in a T-maze. The microinjection of the ionotropic glutamate antagonists 6-cyano-7-nitroquinoxaline-2,3-dione or 3-( R)-2-carboxypiperazin-4-propyl-1-phosphonic acid into the prefrontal cortex impaired working memory. Consistent with a role for glutamate receptor activation, microinjecting the GABA B agonist baclofen into the mediodorsal thalamus produced a dose-dependent disruption of working memory. In contrast, inhibition of the mesocortical dopamine projection was without effect on working memory. The blockade of D 1 and/or D 2 dopamine receptors with SCH-23390 and sulpiride was without effect on working memory. Likewise, the microinjection of baclofen into the ventral tegmental area did not impair working memory. However, stimulating mu-opioid receptors in the ventral tegmental area with [ d-Ala 2, N-Me-Phe 4,Gly-ol 5]enkephalin produced a dose-dependent impairment of working memory that was reversed by blocking D 1 dopamine receptors with SCH-23390 in the prefrontal cortex. These data demonstrate that increased dopamine tone or reduced glutamate tone in the prefrontal cortex disrupts working memory in a spatial delayed alternation task. The integrity of the prefrontal cortex is critical for the expression of working memory. The prefrontal cortex is innervated by dopaminergic afferents from the ventral tegmental area and glutamatergic afferents from the mediodorsal thalamus. To determine the role of dopaminergic and glutamatergic afferents in the regulation of working memory, rats were trained to perform a spatial delayed alternation task in a T-maze. The microinjection of the ionotropic glutamate antagonists 6-cyano-7-nitroquinoxaline-2,3-dione or 3-(R)-2-carboxypiperazin-4-propyl-1-phosphonic acid into the prefrontal cortex impaired working memory. Consistent with a role for glutamate receptor activation, microinjecting the GABA(B) agonist baclofen into the mediodorsal thalamus produced a dose-dependent disruption of working memory. In contrast, inhibition of the mesocortical dopamine projection was without effect on working memory. The blockade of D1 and/or D2 dopamine receptors with SCH-23390 and sulpiride was without effect on working memory. Likewise, the microinjection of baclofen into the ventral tegmental area did not impair working memory. However, stimulating mu-opioid receptors in the ventral tegmental area with [D-Ala2,N-Me-Phe4,Gly-ol5]enkephalin produced a dose-dependent impairment of working memory that was reversed by blocking D1 dopamine receptors with SCH-23390 in the prefrontal cortex. These data demonstrate that increased dopamine tone or reduced glutamate tone in the prefrontal cortex disrupts working memory in a spatial delayed alternation task. |
Author | Kalivas, P.W Duffy, P Romanides, A.J |
Author_xml | – sequence: 1 givenname: A.J surname: Romanides fullname: Romanides, A.J – sequence: 2 givenname: P surname: Duffy fullname: Duffy, P – sequence: 3 givenname: P.W surname: Kalivas fullname: Kalivas, P.W |
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Keywords | VTA, ventral tegmental area prefrontal cortex CPP, 3-( R)-2-carboxypiperazin-4-propyl-1-phosphonic acid DAMGO, [ d-Ala 2, N-Me-Phe 4,Gly-ol 5]enkephalin MCPG, ( RS)-α-methyl-4-carboxyphenylglycine DMSO, dimethylsulfoxide ventral tegmental area working memory AMPA, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate mediodorsal thalamus CNQX, 6-cyano-7-nitroquinoxaline-2,3-dione PFC, prefrontal cortex dopamine NMDA, N-methyl- d-aspartate glutamate Dopamine Rat Rodentia Central nervous system Prefrontal cortex Catecholamine Glutamate Vertebrata Mammalia Animal Excitatory aminoacid Neurotransmitter Thalamus Working memory Ventral tegmental area Brain (vertebrata) Spatial memory |
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SubjectTerms | Animals Behavioral psychophysiology Biological and medical sciences dopamine Dopamine - metabolism Fundamental and applied biological sciences. Psychology glutamate Glutamic Acid - metabolism Male Maze Learning - physiology mediodorsal thalamus Memory - physiology Neurons, Afferent - physiology Neurotransmission and behavior prefrontal cortex Prefrontal Cortex - physiology Psychology. Psychoanalysis. Psychiatry Psychology. Psychophysiology Rats Rats, Sprague-Dawley Receptors, GABA-B - physiology Receptors, Opioid, mu - physiology Space life sciences Space Perception - physiology Synaptic Transmission - physiology Thalamus - physiology ventral tegmental area working memory |
Title | Glutamatergic and dopaminergic afferents to the prefrontal cortex regulate spatial working memory in rats |
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