scious awareness of breathing requires the activation of higher brain centers and is believed to be a neural gated process. The thalamus could be responsible for the gating of respiratory sensory information to the cortex. It was reasoned that if the thalamus is the neural gate, then tracheal obstructions will modulate the gene expression profile of the thalamus. Anesthetized rats were instrumented with an inflatable cuff sutured around the trachea. The cuff was inflated to obstruct 2-4 breaths, then deflated for a minimum of 15 breaths. Obstructions were repeated for 10 min followed by immediate dissection of the medial thalamus. Following the occlusion protocol, 588 genes were found to be altered (P Ͻ 0.05; log2 fold change Ն 0.4), with 327 genes downregulated and 261 genes upregulated. A significant upregulation of the serotonin HTR2A receptor and significant downregulation of the dopamine DRD1 receptor genes were found. A pathway analysis was performed that targeted serotonin and dopamine receptor pathways. The mitogen-activated protein kinase 1 (MAPK1) gene was significantly downregulated. MAPK1 is an inhibitory regulator of HTR2A and facilitatory regulator for DRD1. Downregulation of MAPK1 may be related to the significant upregulation of HTR2A and downregulation of DRD1, suggesting an interaction in the medial thalamus serotonin-dopamine pathway elicited by airway obstruction. These results demonstrate an immediate change in gene expression in thalamic arousal, fear, anxiety motivation-related serotonin and dopamine receptors in response to airway obstruction. The results support the hypothesis that the thalamus is a component in the respiratory mechanosensory neural pathway. respiratory loading; microarray; stress; serotonin; dopamine THE RESPIRATORY SYSTEM is continually active, and any prolonged interruption is a threat to an animal's survival. Thus it is of critical importance to maintain ventilation in the face of a variety of stimuli by adjusting the breathing pattern. Clark and von Euler (13) described the relationship between lung volume and breath timing in anesthetized cats. They demonstrated that inspiratory time (TI) depends on inspiratory volume and that the subsequent expiratory time (TE) depends on the preceding TI. A similar volume-timing relationship was found when a mechanical stimulus in the form of an external resistive load was applied. Loading of the inspiratory (57) or expiratory (33) phase caused a decrease in volume and an increase in the duration of the respective loaded breath phase. The response to the added loads was called the respiratory load compensation reflex. Load compensation is a sensory motor response.A sufficiently high load on the respiratory system results in the sensation of dyspnea, or breathlessness, which is one of the primary symptoms in pulmonary and cardiovascular diseases (40, 44). It is one of the main symptoms that limits patients with obstructive pulmonary diseases, and it can also be considered one of the most important factors in determining the severi...