Induction of hippocampal theta rhythm by electrical stimulation of the ventral tegmental area and its loss after septum inactivation

The ventral tegmental area (VTA), which may be one of the structures involved in regulation of hippocampal theta rhythm, sends direct projections to the hippocampus and also to the forebrain septum, the key centres involved in theta generation. In the present study we aimed at assessing which projections from the VTA (direct or through the septum) participate in regulation of hippocampal electric activity. Experiments were conducted on 3 groups of urethanised male Wistar rats. In the first group (n=6) electrical stimulation of the VTA was used to evoke theta rhythm episodes in hippocampus. Stimulation was repeatedly applied in control conditions and after procainic blockade of the septum. The second group (n=6), subjected to unilateral electrical stimulation of the VTA (30-s stimulation at 10-min intervals during 2 h) and to subsequent detection of Fos expression, served to measure neuronal activation of the target mesolimbic structures. Activation levels of selected structures were compared to data from analogous stimulation of the zona incerta (ZI, the third group, n=6). Stimulation of the VTA immediately generated regular theta rhythm in both hippocampi. Inactivation of the septum with procaine temporarily abolished this effect. VTA stimulation increased the density of Fos in the ipsilateral nucleus accumbens. Stimulation of the ZI never generated theta but evoked significant induction of Fos expression in the hippocampus. Our data suggest that the projection through which the VTA enhances theta rhythm is not direct but is incorporated into the main route of theta generation, which involves septum as the main relay node. (C) 2011 Elsevier B.V. All rights reserved.