Selective behavioral and neurochemical effects of cholinergic lesions produced by intrabasalis infusions of 192 IgG-saporin on attentional performance in a five-choice serial reaction time task

The effects of the cholinergic immunotoxin 192 IgG-saporin (SAP) (0.0, 0.15, or 0.45 mug/mul; 0.5 mul/hemisphere) infused into the area of the nucleus basalis magnocellularis (NBM) of rats were tested in a five-choice serial reaction time task (5CSRTT) designed to assess visual attention. The effects of this manipulation on acetylcholine efflux in the medial frontal cortex were determined using in vivo microdialysis during the 5CSRTT. Rats with extensive lesions of the NBM (SAP HIGH) showed an array of behavioral deficits in the 5CSRTT hypothesized to represent deficits in central executive function that were associated with severe deficits in accuracy. Lengthening the stimulus duration ameliorated these deficits. Rats with restricted lesions of the NBM (SAP LOW) showed impairments over time on task when tested under standard conditions that were exacerbated by increases in the event rate. The number of choline acetyl-transferase-immunoreactive cells in the area of the NBM but not the vertical limb of the diagonal band correlated significantly with accuracy in the task. SAP HIGH rats had significantly lower levels of cortical acetylcholine (ACh) efflux relative to SHAM both before and during the 5CSRTT. SAP LOW rats showed significantly higher levels of cortical ACh efflux before but not during the 5CSRTT. Cortical ACh efflux increased in all rats with the onset of the attentional task. These data provide the first direct evidence for a relationship between selective damage in the basal forebrain with decreased cortical ACh efflux and impaired attentional function.