Effect of N-methyl-d-aspartate receptor blockade on plasticity of frontal cortex after cholinergic deafferentation in rat.
Cholinergic projections from the nucleus basalis play a critical role in cortical plasticity. For instance, cholinergic deafferentation increases dendritic spine density and expression of the GluR1 subunit of the alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate receptor in frontal cortex. Acetylcholine modulates glutamatergic activity in cortex, and the N-methyl-d-aspartate subtype of glutamate receptor plays a role in many forms of synaptic plasticity. To assess whether N-methyl-d-aspartate receptors mediate the increase in GluR1 and spine density resulting from cholinergic deafferentation, we examined the effect of N-methyl-d-aspartate receptor blockade on nucleus basalis lesion-induced upregulation of GluR1 and dendritic spines. Rats received unilateral sham or 192 IgG saporin lesions of the nucleus basalis. Half of the rats in each group were treated with the N-methyl-d-aspartate antagonist MK-801 or phosphate-buffered saline. Two weeks later, brains were processed for either immunohistochemical staining of the GluR1 subunit or Golgi histology. In layer II-III of frontal cortex, neuronal GluR1 expression was assessed using an unbiased stereological technique, and spine density was assessed on basilar branches of pyramidal neurons. GluR1 expression was increased after nucleus basalis lesion, but this increase was prevented with MK-801. Similarly, nucleus basalis-lesioned animals had significantly higher spine densities, and this effect was also prevented by treatment with MK-801. Thus, N-methyl-d-aspartate receptor blockade prevented both GluR1 and spine density upregulation following cholinergic deafferentation, suggesting that these effects are N-methyl-d-aspartate receptor-mediated.
Garrett
J E
JE
Department of Psychological and Brain Sciences, Indiana University, Bloomington, IN 47405, USA.
Kim
I
I
Wilson
R E
RE
Wellman
C L
CL
D000818:Animals; D000911:Antibodies, Monoclonal / Q000633:toxicity; D002452:Cell Count / Q000379:methods; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D018678:Cholinergic Agents / Q000633:toxicity; D002799:Cholinergic Fibers / Q000187:drug effects / Q000378:metabolism*; D003714:Denervation / Q000379:methods; D016291:Dizocilpine Maleate / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005625:Frontal Lobe / Q000166:cytology*; D007839:Functional Laterality; D007150:Immunohistochemistry / Q000379:methods; D000922:Immunotoxins / Q000633:toxicity; D009699:N-Glycosyl Hydrolases; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D051381:Rats; D018091:Receptors, AMPA / Q000037:antagonists & inhibitors / Q000502:physiology*; D054789:Ribosome Inactivating Proteins, Type 1; D000076985:Saporins; D016622:Silver Staining / Q000379:methods; D013131:Spine / Q000378:metabolism / Q000648:ultrastructure
D000911:Antibodies, Monoclonal; D002795:Choline O-Acetyltransferase; D018678:Cholinergic Agents; D016291:Dizocilpine Maleate; D018691:Excitatory Amino Acid Antagonists; D000922:Immunotoxins; D009699:N-Glycosyl Hydrolases; D018091:Receptors, AMPA; D054789:Ribosome Inactivating Proteins, Type 1; D000076985:Saporins; C085696:192 IgG-saporin