In a variety of developmental contexts, specific coordination of synaptic excitability shapes a history of neuronal communication that has an important impact on the future network’s behavior. However, questions persist about what kind of machinery and mechanisms may selectively regulate a given type of activity in neuronal circuitries. Some emerging evidences point to direct interactions between pre- and postsynaptic adhesive molecules – such as neurexins and neuroligins – that play an essential role in differentiation of synaptic connections. In addition, the trans-synaptic heterophilic adhesion complex formed by these molecules provides diverse functional consequences, including regulation of the balance between inhibition and excitation as well as modulation of pre- and postsynaptic functional properties. Although considerable progress has been made in recent years to understand the physiological importance of neurexins and neuroligins, little is known about some of the members of these cell-adhesion proteins. In the present work, the synaptic specificity and physiological relevancies of neurexin-2α/β isoforms and neuroligin‑4 were tested for the first time by using genetically modified in vivo models to shed more light on functional consequences attributed to these members of the neurexin/neuroligin family.