In order for these inhibitory interneurons to act upon their targets, they must receive input from a gatekeeper signal that stimulates them. This input can be either intrinsic, extrinsic or both. Extrinsic input comes from an area of the brain anatomically and functionally distinct from a given circuit, while intrinsic input is released from parts if the circuit itself. Generally, this input occurs in the form of neuromodulatory substances, such as hormones, neuropeptides and other neurotransmitters that have been released from incoming neurons. These signals then converge on the gatekeeper, where they are integrated and directed toward the target. Depending on the circuit, gate signals may arrive from different brain areas. For example, studies have shown that the entorhinal cortex may gate areas of the medial PFC, thereby inhibiting them from projecting to other brain areas.