David C. Martinelli, PhD

A synapse is the fundamental structural unit by which neurons communicate. The importance of synapses cannot be overstated as their collective activities impact every moment of our subconscious and conscious mind. Furthermore, synapses are formed and continuously restructured throughout life based on different experiences, which ultimately shapes us as individuals with unique memories, thoughts, skills, and personalities. How the trillions of synapses in a brain are wired into functional neural networks and the mechanisms of experience-dependent synaptic plasticity are important outstanding questions. I am particularly fascinated by synaptic adhesion proteins, which bind across the synaptic cleft to form a molecular interface between pre- and post-synaptic membranes and also initiate intercellular trans-synaptic signaling. These proteins are at the junction of our genes and experiences and are critical for initiating and stabilizing synaptic changes in a multitude of ways. My research goal is to understand the molecular logic of how synaptic adhesion proteins, in a defined brain circuit, orchestrate synaptic formation, modification, and function, and to ultimately provide an explanation for how these events influence behaviors, in particular the aberrant behaviors associated with neuropsychiatric diseases. The immediate focus of my research is on the neuronally secreted C1q-like family of proteins. The lab will study the biochemical interactions with their pre- and post-synaptic protein binding partners, their synaptic signaling activities, and their eventual behavioral consequences. A priori, their localization in the synaptic cleft almost predestines them to have neuropsychiatric disease relevance. Genetic analyses of C1q-like mutant mice revealed behavioral abnormalities potentially resembling several neuropsychiatric diseases, including ADHD, schizophrenia, and addiction predisposition. How C1q-like proteins and their binding partners influence synapses and ultimately behaviors is unknown. The techniques used in the lab to answer these questions encompass biochemistry, genetics, cell biology, circuit analysis using viral vectors, and mouse behavioral assays.

[2026] Backbone resonance assignment of the pentraxin domain of the neuronal pentraxin receptor (NPTXR). [2025] C1ql3 promotes cognitive flexibility behavior in mice. [2024] Stepwise molecular specification of excitatory synapse diversity onto cerebellar Purkinje cells. [2024] C1ql1 expression in oligodendrocyte progenitor cells promotes oligodendrocyte differentiation. [2024] Creation of a novel CRISPR-generated allele to express HA epitope-tagged C1QL1 and improved methods for its detection at synapses.