Figure 2.

A schematic diagram of putative processing models in the differences of neuronal manipulation by drugs/ligands administration and the DREADD application. Drug administration induces humoral processes widely distributing drugs throughout the body via osmotic and circulation drive. Compounds of the drugs penetrate into the neurons and synaptic clefts and ultimately bind to several receptors in its affinity dependent manner. The locations of receptors include pre- and post-synapses and axonal tracts. Therefore, the total outputs of neural firing stimulated by drug administration will reflect combined effects of agonism and antagonism of drug stimulations, which would be read out as non-linear quantitative effects on the output of neuronal firing. On the other hand, the DREADDs application can archive cell- or circuit-specific manipulation of the simple output from the target neuronal node, which allows to investigate the neuron specific function on regulating particular behavior.