Copper ions (Cu2+) in the central nervous system play a crucial role in the physiological and pathological events, so simple, selective, and sensitive detection of cerebral Cu2+ is of great importance. In this work, we report a facile yet effective fluorescent method for sensing of Cu2+ in rat brain using one kind of lanthanide coordination polymer nano-particle, adenosine monophosphate (AMP) and terbium ion (Tb2+), i.e., AMP-Tb, as the sensing platform. Initially, a cofactor ligand, 5-sulfosalicylic acid (SSA), as the sensitizer, was introduced into the nonluminescent AMP-Tb suspension, resulting in switching on the luminescence of AMP-Tb by the removal of coordinating water molecules and concomitant energy transfer from SSA to Tb2+. The subsequent addition of Cu2+ into the resulting SSA/AMP-Tb can strongly quench the fluorescence because the specific coordination interaction between SSA and Cu2+ rendered energy transfer from SSA to Tb2+ inefficient. The decrease ratio of the fluorescence intensities of SSA/AMP-Tb at SSO nm show a linear relationship for Cu2+ within the concentration range from 1.5 to 24 mu M with a detection limit of 300 nM. The method demonstrated here is highly selective and is free from the interference of metal ions, amino acids, and the biological species commonly existing in the brain such as dopamine, lactate, and glucose. Eventually, by combining the microdialysis technique, the present method has been successfully applied in the detection of cerebral Cu2+ in rat brain with the basal dialysate level of 1.91 +/- 0.40 mu M (n = 3). This method is very promising to be used for investigating the physiological and pathological events that cerebral Cu2+ participates in.