Relative contribution of brainstem afferents to the cocaine- and amphetamine-regulated transcript (CART) innervation of thyrotropin-releasing hormone synthesizing neurons in the hypothalamic paraventricular nucleus (PVN)

To determine the relative contribution of the brainstem to the CART innervation of the TRH neurons in the PVN, the major ascending brainstem axonal pathways to the PVN were unilaterally transected in the hypothalamus. After 2 weeks survival time, hypothalamic sections were prepared for immunocytochemistry. PNMT-IR axon density decreased 76.0 ± 3.8% on the side of the knifecut compared to the contralateral side, demonstrating satisfactory disconnection of the ascending brainstem pathways. In contrast, the density of CART-IR axons in the PVN on the lesioned side was reduced by only 26.9 ± 2.7%. Disconnection of brainstem pathways reduced the total number of TRH neurons contacted by CART from 99.4 ± 0.9% on the intact side to 74.3 ± 9.4% on the lesioned side, as well as the number of CART varicosities on the surface of TRH neurons from 6.0 ± 0.9 to 2.3 ± 0.4 CART-IR varicosities/cell. These data indicate that CART-IR neurons residing in the brainstem give rise to only approximately one third of the CART input to the PVN as a whole, but serve as a major source of the CART-IR innervation of hypophysiotropic TRH neurons.