All species exhibit critical period for sensory development, yet very little is known about the molecules involved in the changes in the network wiring that underlies this process. Here the role of brain-derived neurotrophic factor (BDNF) in the critical period of thermal control establishment in chicks was investigated. Neuroanatomically, the body temperature is balanced by the preoptic anterior hypothalamus (PO/AH) and controlled by thermosensitive neurons. Exposure to hot or cold conditions during the critical period of temperature control development causes a plastic change in the ratio between heat- and cold-sensitive cells and can modulate temperature tolerance. It was found that expression of BDNF mRNA but not of NGF or neurotrophin-3 was induced in the PO/AH of 3-d-old chicks during both heat and cold exposure. The peak of BDNF induction in both heat and cold exposure occurred after 6 h, with, respectively, threefold and sevenfold increases in its mRNA expression. To prove the concept that BDNF activation is a critical step in thermal-experience-dependent plasticity, BDNF was "knocked down" using antisense. It was found that, when BDNF in the PO/AH was inhibited by 80% during the third postnatal day, thermal establishment was impaired, and, after 1 week, the chicks' body temperature was reduced by 0.5 degrees C. Furthermore, later in life, their reaction to thermal challenge was altered, and they exhibited a pronounced reduction in their ability to maintain their body temperature and body weight under harsh conditions. Together, these results prove that BDNF is critically involved in thermal-experience-dependent development.