Neuroligins, synapse balance and neuropsychiatric disorders

Neuroligins are postsynaptic adhesion molecules that are involved in the regulation of synapse organisation and function. Four neuroligin proteins have been identified (neuroligin 1, 2, 3, 4), which are differentially enriched in the postsynaptic specialisation of synapses. Neuroligin 1 is localised on excitatory (glutamatergic) synapses, whereas neuroligin 2 is located on inhibitory (GABAergic/glycinergic) synapses. Neuroligin 3 and 4 are present on both types of synapses. Recent data indicate that neuroligins are involved in synapse maturation and specification. Because of their synaptic localisation and function, neuroligins control the balance between excitatory and inhibitory synapses. Animal studies with neuroligin transgenic mice showed the involvement of neuroligin 1 in memory formation, and neuroligin 2, 3 or 4 in social behaviour. Interestingly, genetic analysis of humans showed a mutation in the neuroligin 2 gene in schizophrenic patients, while mutations in neuroligin 3 or 4 genes were found in autism.