Identification of the hypothalamic site through which locus coeruleus axons decussate to reach and stimulate contralateral LH-RH neurons

Abstract

Recently we reported that locus coeruleus (LC) electrical stimulation (ES) amplifies the quantity of LH released prior medial preoptic nucleus (MPN)-electrochemical stimulation (ECS). In these studies we also observed that amplification of LH release occurred only when we activated those LC neurons whose cell bodies reside contralateral to the site of MPN-ECS. Seemingly, stimulatory LC axons decussate to reach contralateral hypothalamic regions which contain LH-RH neurons. The purpose of the present study was to identify the site(s) at which such decussation(s) occur. To accomplish this we used a special knife blade to make gross transections in hypothalamic regions previously described by others as regions where LC decussations occur. Transection 1 (TI) interrupted axons coursing through the medial forebrain bundle (MFB) in the region of the posterior lateral hypothalamus. This transsection was placed ipsilateral to the side of LC-ES and it had no effect on LH patterns of concentrations which were released by MPN-ECS. However, T1 completely blocked the amplifying effects of LC stimulation on LH secretion after MPN-ECS. Transection 2 (T2) was placed in the region of the MPN, parallel to the superior sagittal sinus. The knife blade was lowered in midline to the top of the 3rd ventricle and transected all fibers which cross midline within and around the anterior commissure. LH release following MPN-ECS was not appreciably affected in these rats nor did T2 alter the amplifying effects of LC-ES on LH. However, while plasma LH peaked between 60 and 75 min and then declined towards baseline in MPN + LC-stimulated rats, it remained significantly elevated throughout the remainder of the blood collection periods (180 min) in rats receiving combined MPN + LC and T2. Transection 3 (T3) also was placed in the MPN region and differed from T2 only in that we lowered the knife to the base of sphenoid bone. Thus, T3 disrupted all fibers which cross midline in the AC region and dorsal to the optic chiiasm (dorsal supraotic decussation of LC axons). This transection did not affect LH release evoked by MPN-ECS but completely eliminated the amplifying effects of LC stimulation after MPN-ECS on LH secretion. These data indicate that stimulatory LC axons which affect LH-RH neuronal activity enter the hypothalamus ipsilateral to the site of LC-ES and then project rostrally in the MFB to the lateral preoptic area. In this region, certain stimulatory LC fibers leave the MFB and cross midline in the dorsal supraoptic decussation to reach the contralateral MPN where they affect LH-RH neuronal activity. The data obtained in rats with AC transections (T2) also suggest that inhibitory inputs from extrahypothalamic regions enter the hypothalamus and suppress or arrest LH-RH release. Disruption of these inhibitory preoptic projections results in the sustained secretion of elevated levels of LH-RH/LH following MPN + LC stimulation.