The contribution of anterior medial forebrain bundle neurons to self-stimulation of the lateral hypothalamic and ventral tegmental areas

Identification of the reward-relevant neurons activated by stimulation of the medial forebrain bundle (MFB) has been a major goal of research in the area of brain stimulation reward. In a series of experiments, the contribution of neurons in the anterior MFB to the rewarding effect of stimulating more caudal MFB sites was examined. In Experiment 1, the effect of anterior lateral hypothalamic (ALH) lesions on the frequency threshold for self-stimulation of the middle lateral hypothalamus (LH) and ventral tegmental area (VTA) was determined. In 5 out of 14 subjects, lesions to the ALH and surrounding regions resulted in long-lasting increases (0.1-0.25 log$\\sb�$ units) in the frequency threshold for self-stimulation of the LH or VTA, an effect consistent with a reduction in the rewarding effectiveness of the stimulation. In Experiment 2, the paired-pulse collision technique was used to determine whether reward-relevant neurons directly link the VTA and the site previously lesioned in the ALH. Stimulation consisted of trains of pulse pairs, with each electrode receiving one pulse from each pair. It was reasoned that if each stimulation site lay along the trajectory of the same reward-relevant axons, then collision of antidromic and orthodromic action potentials should occur when stimulating at short inter-pulse intervals, thus resulting in a decrease in the effectiveness of the stimulation. Significant collision-like effect were obtained in 4 of the 6 subjects, supporting the notion that reward-relevant neurons directly link the ALH and VTA. In Experiment 3, extracellular recordings were obtained from cells in the rostral bed nucleus of the MFB that were antidromically activated by stimulation of posterior MFB sites that typically support self-stimulation. The refractory periods and conduction velocities of descending MFB fibers arising from these cells were similar to those obtained for reward-relevant MFB neurons using psychophysical methods. This work suggests that neurons arising in the anterior MFB may be part of the directly-activated substrate for rewarding MFB stimulation.