Unconventional transmitters and neurodegeneration

Research in our laboratory focuses on understanding the roles of unconventional neurotransmitters, like the D-amino acids in the central nervous system. We are pioneers in studying the neurobiology of D-serine, a D-amino acid now widely appreciated as a transmitter/signaling molecule in the brain. D-Serine is required for the activity of a critical neurotransmitter receptor- the NMDA receptor (NMDAR)- and mediates learning and memory as well as neurodegeneration. In the last few years, our studies unraveled mechanisms underlying brain D-serine production, physiological roles, cellular sources, metabolism, and its role in pathology. This research helped to pave the way for establishing D-serine as a signaling molecule in health and disease. In addition to neurotransmission, NMDARs play a crucial role in neurodegeneration, with their excessive activation contributing to neuronal death in several neurodegenerative disorders, such as Alzheimer’s disease. We discovered that D-serine is the dominant NMDAR co-agonist mediating neurotoxicity, raising the possibility that drugs that curb D-serine synthesis or release might be useful in neurodegenerative diseases involving NMDAR over-stimulation.

 

Another research goal is to discover novel metabolic pathways controlling neurotransmission and astroglia-neuron cross-talk. We recently identified new molecular components of a metabolic crosstalk we coined the “serine shuttle” (See our recent paper), whereby astrocytes regulate synaptic plasticity and neurodevelopment by exporting L-serine for the neuronal synthesis of D-serine.

 

Our studies employ a wide range of techniques, including molecular biology, cell biology, in vivo brain microdialysis, brain imaging, electrophysiology, RNAseq, animal behavior, and novel mice genetic models to uncover new molecular components that regulate the serine shuttle. These models will allow the identification of novel pathways that participate in glia-neuron cross-talk and neurodegenerative processes.

 The lab is recruiting new students !!