THE DISTRIBUTION OF NEURONS COEXPRESSING IMMUNOREACTIVITY TO AMPA-SENSITIVE GLUTAMATE-RECEPTOR SUBTYPES (GLUR1-4) AND NERVE GROWTH-FACTOR RECEPTOR IN THE RAT BASAL FOREBRAIN

The regional distribution of neurons containing alpha-amino-3-hydroxy- 5-methyl-4-isoxazole propionic acid (AMPA) receptor (GluR1-4) subunit immunoreactivity, relative to the distribution of cholinergic neurons within the basal forebrain of rats, was assessed using single- and dua l-antigen immunocytochemistry. Analysis of serial sections stained wit h antibodies to nerve growth factor receptor (NGFr) and antibodies aga inst each of the AMPA receptor subunits, GluR1-4, revealed a regional codistribution between NGFr- and GluR1- and GlUR4-immunoreactive neuro ns in the medial septum, diagonal band nuclei and nucleus basalis magn ocellularis. Quantitative dual-labelling immunocytochemistry using NGF r in combination with each of the GluR antibodies revealed >65% coloca lization between NGFr and GluR4 in each of the major cholinergic nucle i in the basal forebrain and 10-15% colocalization between NGFr, GluR1 and GluR2-3. The reticular nucleus of the thalamus, a structure known to be highly susceptible to AMPA-induced neurotoxicity, expressed Glu R4 immunoreactivity exclusively. The observation that cholinergic neur ons of the basal forebrain are also highly sensitive to AMPA and expre ss the GluR4 subunit suggests that GluR4 may be important in AMPA rece ptor-mediated excitotoxicity.