Noncholinergic lesions of the medial septum impair sequential learning of different spatial locations

The medial septum and diagonal band of Broca (MSDB) are major afferents to the hippocampus and are important for learning, memory, and hippocampal theta rhythm. In the present study, we assessed the effect of cholinergic or noncholinergic MSDB lesions on the sequential learning of different goal locations in the same environment, a type of task that is proposed to require hippocampal theta rhythm. Rats were administered saline, 192-IgG saporin (SAP), or kainic acid (KA) into the MSDB and then behaviorally tested. On any day, a single arm of a radial maze was rewarded with food, but the location of this rewarded arm changed between days. As in previous studies, intraseptal SAP reduced the number of cholinergic neurons although sparing GABAergic septohippocampal neurons. KA had the reverse effect, reducing GABAergic septohippocampal neurons and sparing cholinergic neurons. KA, but not SAP, impaired performance on the repeated acquisition task. Saline and SAP rats showed rapid within-session learning, whereas KA rats were much slower to learn the goal location. Performance on a 30 min retention trial was also impaired, although this may be attributable to incomplete acquisition. These findings provide evidence that noncholinergic, but not cholinergic, MSDB neurons are important in helping the animal deal with high loads of memory interference, and provides partial support for the idea that hippocampal theta rhythm is involved.