Synapses are the structures that connect neurons into functional networks. Modulation is central to brain function at every level, from information processing to memory storage and on to adaptive behavior. Scientists in our program investigate the underlying mechanisms and molecules, and how they operate in brain circuits that mediate cognition, learning and emotion or generate motor output or social interactions. We use a broad range of approaches including: molecular genetics; cell biology and biochemistry; 3D-ultraresolucion tracing of networks; ex vivo and in vivo electrophysiology; RNAseq analysis; chemical and optogenetics; and behavioral analyses. A common goal is to translate the discoveries into strategies for treating brain diseases such as Parkinson’s disease and autism-spectrum disorders, and to promote healthy aging. To date, we have identified multiprotein complexes that mediate long-lasting memory encoding and might provide targets for antidepressant and cognitive enhancement strategies, and have linked single-copy variations in kainate receptors to behavioral deficits in autism.