Experimental manipulations that compromise the medial septal area cons
istently and selectively impair working memory. The electrophysiologic
al and pharmacological properties of medial septal neurons have been s
tudied extensively, but the relation between medial septal neuronal ac
tivity and ongoing behavior has not been systematically analysed. Work
ing memory was assessed in a continuous conditional discrimination tas
k, and behavioral performance was correlated with medial septal single
unit activity. Operant performance and the activity of rhythmically a
ctive neurons were continuously monitored during a 90 min test session
, and peri-event time histograms of unit activity were constructed aro
und relevant task events. Rats received intraperitoneal injections of
either saline or ethanol (0.75 g/kg) 5 min before testing. Of the 52 m
edial septal neurons recorded under saline conditions, approximately 8
0% had significant behavioral correlates. Thirty-five per cent of thes
e neurons were selectively activated at the time of the response and 6
5% at the time of the reward. Response-related activity was not select
ive for responses to the right or left lever, or to a particular type
of trial, but in 61% of the cases was correlated with the accuracy of
the response. In ethanol-treated rats, working memory was impaired, si
ngle unit activity was disrupted, and the behavioral correlates were l
ess frequent and robust, especially the response-related correlates th
at were accuracy-sensitive. The results suggest that the medial septal
area is involved in guiding accurate responses and processing rewards
, and may contribute to the ethanol-induced impairments in working mem
ory.