Neuroligins Differentially Mediate Subtype-Specific Synapse Formation in Pyramidal Neurons and Interneurons / 神经科学通报·英文版

Neuroligins (NLs) are postsynaptic cell-adhesion proteins that play important roles in synapse formation and the excitatory-inhibitory balance. They have been associated with autism in both human genetic and animal model studies, and affect synaptic connections and synaptic plasticity in several brain regions. Yet current research mainly focuses on pyramidal neurons, while the function of NLs in interneurons remains to be understood. To explore the functional difference among NLs in the subtype-specific synapse formation of both pyramidal neurons and interneurons, we performed viral-mediated shRNA knockdown of NLs in cultured rat cortical neurons and examined the synapses in the two major types of neurons. Our results showed that in both types of neurons, NL1 and NL3 were involved in excitatory synapse formation, and NL2 in GABAergic synapse formation. Interestingly, NL1 affected GABAergic synapse formation more specifically than NL3, and NL2 affected excitatory synapse density preferentially in pyramidal neurons. In summary, our results demonstrated that different NLs play distinct roles in regulating the development and balance of excitatory and inhibitory synapses in pyramidal neurons and interneurons.

Altered GABAergic Signaling in Brain Disease at Various Stages of Life

In the healthy brain, gamma-aminobutyric acid (GABA) is regulated by neurons and glia. This begs the question: what happens in the malfunctioning brain? There are many reasons why diseases occur, including genetic mutations, systemic problems, and environmental influences. There are also many ways in which GABA can become dysregulated, such as through alterations in its synthesis or release, and changes in systems that respond to it. Notably, dysregulation of GABA can have a large impact on the brain. To date, few reviews have examined brain diseases in which dysregulation of GABA is implicated as an underlying factor. Accordingly, the time is ripe for investigating alterations in GABAergic signaling that may play a role in changes in neuronal activity observed in the major brain disorders that occur during various stages of life. This review is meant to provide a better understanding of the role of GABA in brain health and contributor to social problems from a scientific perspective.