Medial septal modulation of entorhinal single unit activity in anesthetized and freely moving rats

Reversible inactivation of the medial septal area results in a spatial memory impairment and selective disruption of hilar/CA3, but not CA1, location-specific discharge. The present study examined the possibility that such septal deafferentation produces effects on hippocampal function by altering physiological properties of the primary input and output structures for hippocampus, the entorhinal cortex and the subiculum, respectively. Single unit activity of hippocampal, entorhinal, and subicular cells was recorded before, during, and after septal injection of lidocaine in anesthetized rats. When compared to hippocampal cells, relatively few subicular and entorhinal cells showed a change in mean firing rate following septal inactivation. Entorhinal unit responses to septal inactivation (via tetracaine injection) were also examined in freely moving rats performing a spatial maze task. About one-third of entorhinal cells showed enhanced or reduced firing rates of 40% or more. Also, the spatial distribution of cells found in the superficial, but not deep, entorhinal layers became less clear following septal inactivation. Together, these data are consistent with the hypothesis that manipulation of the medial septum affects hippocampal function via its septosubicular and septoentorhinal projections in addition to the more direct septohippocampal pathway. Since entorhinal cortical function was affected by tetracaine injection into the septum, it does not appear that direct entorhinal-CA1 afferents were primarily responsible for the maintenance of CA1 location-specific neural activity in previous septal inactivation experiments. Rather, these data are consistent with the hypothesis that the persistence of CA1 place fields was accomplished by intrahippocampal neural network operations.