 Every brain function, from consciousness to motor control, depends on communication between brain cells called neurons. The vast majority of this communication occurs through specialized point-to-point contacts called synapses, which consist of a pre- and a post-synaptic compartment. In response to stimulation, a neuron releases signaling molecules called neurotransmitters from the pre-synaptic compartment. Subsequently, the neurotransmitter binds to receptors on the post-synaptic compartment of the downstream neuron, generating another electrical signal. The release of neurotransmitters from the pre-synapse is heavily regulated through a complex of proteins at the site of release, the active zone. However, the precise role of many of these proteins has remained unclear. Researchers recently demonstrated that two of these proteins, GIT1 and GIT2, regulate synaptic communication through distinct pre-synaptic mechanisms. GIT1 and GIT2 are members of a family of proteins that were first found to interact with G-protein-coupled kinases and other proteins that regulate many signaling pathways in cells. GITs have been implicated in cognitive functions such as learning and memory, as well as in disorders such as Huntington's disease and attention deficit hyperactivity disorder, or ADHD. Although the function of GITs in the post-synapse has been characterized, the role of GITs in the pre-synapse has remained unknown. Part of the problem is that pre-synapses are usually too small to probe directly and that GIT proteins are expressed in both the pre- and post-synaptic compartments. In this study, the researchers therefore selectively eliminated GIT expression from the calyx of Held, a giant pre-synapse in the auditory brainstem. They then used tiny microelectrodes to record electrical activity from both the calyx itself and the post-synaptic cells that the calyx communicates with in mouse brain slices to determine how synaptic communication was affected by the specific loss of GITs in the pre-synapse. When both GIT1 and GIT2 were eliminated from the calyx, post-synaptic responses were larger, demonstrating that pre-synaptic GITs regulate the strength of synaptic transmission. Further analyses showed that the absence of GIT1 in particular increased the likelihood that neurotransmitters would be released from the pre-synapse. Regardless of whether GIT1, GIT2, or both were deleted, the structure of the calyx and pre-synapse, as well as pre-synaptic calcium signaling, remained unaffected, which is important because these factors could potentially influence neurotransmitter release. Taken together, these findings indicate that GITs regulate synaptic signal strength primarily by GITs modulation of the efficiency of neurotransmitter release. This study is the first to demonstrate that GIT proteins are important pre-synaptic regulators of synaptic communication. Future studies may investigate how GIT proteins and their pre-synaptic signaling pathways relate to neurological disorders like Huntington's disease and ADHD and other sensory deficits.