Research
The Lichtman lab focuses on uncovering the fine structure of developing and mature neural circuits using new tissue preparation and imaging techniques, that provide synapse-level descriptions of brain structure in a wide variety of animals including Cnidaria, Gastropods, Nematodes, Zebrafish, Rodents, and humans. The lab is currently involved in a consortium developing the approaches required to obtain a full mouse brain connectome.
Research in the Lichtman lab focuses on the study of neural connectivity and how it changes as animals develop and age. With our colleagues we have developed a number of tools that permit synaptic level analysis of neural connections. These include activity dependent uptake of fluorescent dyes, transgenic approaches to label individual nerve cells, and “combinatoric” methods (e.g., DiOlistics, Brainbow, and NPS) to label many nerve cells in the same tissue. In addition, we have helped develop automated electron microscopy approaches for large scale neural circuit reconstruction. These connectomic methods seek to make it routine to acquire neural circuit data in any nervous system.
Our lab is also interested in the mechanisms that underlie synaptic competition between neurons that innervate the same target cell. Much of this work has centered on the mammalian peripheral nervous system which undergoes profound activity-dependent circuit reorganizations in early life. These alterations allow axons to prune most of their synaptic branches while strengthening a small subset of synapses in a competitive process called synapse elimination. Such competitive interactions are responsible for sharpening the patterns of neural connections during development and may also be important in learning and memory formation. The Lichtman laboratory studies synaptic competition by visualizing synaptic rearrangements directly in living animals using modern optical imaging techniques. We have concentrated on neuromuscular junctions in a very accessible neck muscle in mice where new transgenic animals and other labeling strategies allow individual nerve terminals and postsynaptic specializations to be monitored over hours or months. In addition, we have developed several methods to improve our ability to resolve synaptic structure. One method is the “Brainbow” mouse, in which combinations of distinct fluorescent proteins are stochastically expressed in neurons, resulting in labeling with over a hundred unique hues that allow neighboring neuronal processes to be clearly distinguished from one another. Another technique we have optimized is serial electron microscopy reconstruction. For this we have developed a novel device that makes possible automated ultrathin sectioning of large volumes of brain tissue (several cubic millimeters), called an Automatic Tape-Collecting Lathe Ultramicrotome (ATLUM).
