Direct neuronal projection from a brainstem thermosensitive cell group to the preoptic thermoregulatory center

The preoptic area orchestrates thermoregulatory responses in homeotherm animals and humans. This thermoregulatory center receives thermal information about core body and skin temperatures, and in turn, it induces thermogenic responses. The physiology of effector mechanisms has been described in detail outlining the brain areas participating in the execution of thermal responses. Previous studies have presented evidence of peripheral thermosensation, existence of skin thermoreceptors, participation of spinal and brainstem sensory neurons in thermal stress, but only recently has been identified the first evidence of an ascending neuronal pathway transmitting thermal signal to the preoptic thermoregulatory center. Nevertheless, a few brainstem areas have not been linked to an afferent or efferent thermal pathway and the neuronal network of thermoafferent signals has only partially been identified. In the present study, we identified a distinct ascending neuronal projection that originates from the thermoreactive cells of the peritrigeminal nucleus in the medulla oblongata, and projects to the thermoreactive cells of the medial preoptic area in the hypothalamus of rats. First, we have demonstrated retrogradely labeled thermoreactive neurons in the parabrachial, pontine and peritrigeminal cells following the injection of pseudorabies virus, a retrograde multi-synaptic tract tracer, into the ventrolateral subdivision of the medial preoptic area. Confirming the existence of a direct neuronal connection, we detected biotinylated dextran amine (BDA) containing axonal fibers and boutons around thermoreactive cells of the ventrolateral subdivision of the medial preoptic area after BDA injection into the peritrigeminal nucleus that is known to respond the temperature changes. Our findings indicate the existence of a so far unrecognized ascending direct neuronal pathway that transmits thermal signal from the lower brainstem to the thermoregulatory preoptic center.