Justin H. Trotter, Ph.D.
Assistant Professor
Department of Neurosciences and Neurobiology
University of California, San Diego
Faculty Host: Andrew McCulloch, Ph.D.
Seminar Information
Most synapses in the brain are physically linked to astrocytic processes, forming structures known as tripartite synapses. However, the mechanisms that regulate the formation and function of astrocyte-synapse intercellular junctions remain poorly understood. Synaptic adhesion molecules, which are well-characterized for their roles in synapse formation and
function, are also abundantly expressed by astrocytes, making them prime candidates for bridging these junctions. Many of these molecules are frequently mutated in human neuropsychiatric disorders but have been studied almost exclusively in the context of neuron-neuron interactions. A notable example is the classic presynaptic adhesion molecule, neurexin-
1 (NRXN1), which we have found to be highly expressed in astrocytes and localized to tripartite synapses and vascular endfeet. Heterozygous loss-of-function deletions of NRXN1 are associated with a significantly increased risk for a range of psychiatric disorders, including autism spectrum disorder, schizophrenia, and Tourette syndrome. Using mouse models, we demonstrated that the loss of astrocytic Nrxn1 leads to input-specific changes in the organization and function of hippocampal tripartite synapses, as well as distinct behavioral deficits in long-term memory, sensorimotor gating, and sociability. These findings highlight the potential contribution of astrocytic NRXN1 to the pathogenesis of several common psychiatric disorders.
In ongoing research, my lab aims to further elucidate the role of astrocytic Nrxn1 in the organization, function, and specificity of tripartite synapses, with a particular focus on its involvement in social neural circuits and its response to developmental neuroinflammatory insults. We are also investigating the fundamental principles of astrocyte-synapse contact and communication, particularly in neural circuits governing prosocial behaviors. To achieve these objectives, we are leveraging cutting-edge super-resolution microscopy techniques and innovative tools, such as artificial adhesion molecules, to systematically dissect the molecular and functional architecture of astrocyte-synapse junctions within the tripartite synapse.
Justin Trotter is a newly minted assistant professor in the Department of Neurosciences and Neurobiology. He was recruited through the UCSD FIRST program with the support of the Sanford Institute of Empathy and Compassion. Justin completed his graduate studies at the University of South Florida in Medical Sciences, with Dr. Edwin Weeber where he focused on molecular mechanisms of learning and memory. Prior to starting his PhD, Justin worked on synaptic development in the retina as a research fellow with Dr. Joachim Herz at UTSW.
Justin was a postdoctoral fellow and then instructor in Tom Sudhof’s lab at Stanford University where he focused on the molecular mechanisms of synaptic specification and astrocyte-synapse interactions. This work was funded through several fellowships and grants included an F32 and KO1 from the NIMH, and a Young Investigator Award from the Brain and Behavior Foundation. Justin’s background in advanced methods of microscopy, including super resolution imaging, will take center stage as he launches his own research program focused on deciphering the molecular choreography that underpins astrocyte-neuron interactions and determining how these interactions regulate prosocial behaviors.