AG Michaelsen

In this group, we are dedicated to unraveling the complex mechanisms that shape brain function and contribute to neurological disorders. We focus on three core areas of research:

Spine Plasticity and the Actin Cytoskeleton: Impacts of Chronic Stress and Depression

Spine plasticity is essential for synaptic strength, neural connectivity, and the brain's adaptability. Our research delves deep into the cellular and molecular underpinnings of spine plasticity, specifically focusing on the actin cytoskeleton, a crucial component in spine morphology and dynamics. Dendritic spines, the tiny protrusions on neuronal dendrites, undergo continuous remodeling, which is critical for processes such as learning and memory.
Chronic stress and depression have been shown to adversely affect spine plasticity, leading to structural and functional deficits. These conditions can disrupt the actin cytoskeleton within spines, resulting in decreased spine density and altered spine morphology. Such changes can impair synaptic connectivity and plasticity, contributing to the cognitive deficits observed in these mental health disorders.
By leveraging advanced techniques such as super-resolution microscopy, we aim to visualize the actin cytoskeleton and actin binding proteins directly at synapses and understand the signaling pathways that regulate spine formation, stabilization, and elimination. Additionally, we investigate how chronic stress and depression impact these processes at a molecular level. This detailed analysis helps decode how synaptic strength and plasticity are modulated, ultimately influencing cognitive functions and mental health.

Fragile X Syndrome: Synaptic and Behavioral Deficits

Fragile X syndrome (FXS) is a leading genetic cause of intellectual disability and autism, characterized by a constellation of synaptic and behavioral anomalies. Our research focuses on the synaptic deficits associated with FXS by examining the molecular disruptions at the synapse level. We study how abnormalities in the fragile X mental retardation protein (FMRP) affect synaptic connectivity and plasticity. Utilizing specific mouse models, advanced imaging technologies, and comprehensive behavioral assays, we aim to understand how these synaptic alterations translate to the cognitive and behavioral deficits seen in FXS. By elucidating the underlying mechanisms, we strive to identify potential therapeutic targets to mitigate these deficits and improve the quality of life for individuals with FXS.

Neuroimmune Crosstalk in the Healthy CNS and Synapse Development

The interplay between the immune system and the central nervous system (CNS) is fundamental to brain health, particularly during synapse development. In the healthy CNS, microglia and astrocytes play pivotal roles in maintaining homeostasis, supporting synaptic functions, and facilitating neural plasticity. Microglia are the resident immune cells of the CNS; they constantly survey the neural environment, removing debris, and pruning synapses to refine neural circuits. Astrocytes, on the other hand, provide structural and metabolic support, modulate synaptic transmission, and contribute to the formation and maturation of synapses.
Cytokines, under baseline conditions, act as critical signaling molecules that mediate communication between neurons, microglia, and astrocytes. These cytokines help regulate synaptic plasticity, influence synapse formation, and support neurogenesis. By coordinating these cellular and molecular interactions, the neuroimmune system ensures proper synaptic development and function, which are vital for learning, memory, and overall cognitive health.
Our research aims to elucidate the mechanisms by which microglia and astrocytes, along with cytokine signaling, contribute to synapse development and the maintenance of neural circuitry.