Neuroscience at BU: Imaging structural plasticity of neural circuits that mediate social behavior and cognition
The neocortex is important for motor control, sensory processing and the generation of conscious thought. A hallmark of the neocortex is its organization into circuit modules that consist of precise and stereotyped patterns of connections between populations of neurons. The arrangements of these highly conserved circuits allow populations of neurons to coordinate a wide range of sensory and motor functions that underlie complex cognitive behavior.
The mission of the Cruz-Martín lab is to understand the cellular and molecular mechanisms that guide the development of synaptic connections in the neocortex. In our research we also use different models to understand the pathobiology of neurodevelopmental disorders and to develop optimal pharmacological treatments for these disorders. The systems neuroscience approaches that we use to characterize neural circuit properties in combination with behavioral paradigms provide a powerful way to study the relationship between circuit dysfunction and abnormalities in cognition and social behaviors. We use a variety of tools and techniques to study neural circuit function, including multiplex fluorescent in situ hybridization, gene transfer techniques, in vivo two-photon (2P) imaging of spine dynamics and ensemble activity, in vitro slice electrophysiology with optogenetics and rabies transsynaptic mapping.
The Cruz-Martín lab uses 3D printed miniscopes to image neural activity during social behavior
Many studies have shown that half of all lifetime cases of mental illness begin by age 14. Disorders affecting children may include anxiety disorders, attention deficit hyperactivity disorder (ADHD), autism spectrum disorders, bipolar disorder, depression, eating disorders, and schizophrenia. We hope our studies will bring insights into the basic mechanisms of the developmental wiring of the brain and a better understanding of the pathophysiology of neurodevelopmental disorders.
Mapping neural circuits underlying cognitive function (starter neurons (green) labeled in anterior cingulate cortex)
Part of the Cruz-Martin lab focuses on how immune genes regulate cortical development in the healthy and disease brain. Although the brain has been considered "immune-privileged", many studies suggests a strong connection between the immune and nervous systems in both health and disease. Schizophrenia has a known genetic risk and it is 80% heritable. Recent genome-wide association studies (GWAS) show that the major histocompatibility complex (MHC) has the highest genetic association with SCZ. Our lab is currently focusing on how specific immune genes regulate cortical development. We also are trying to understand how early life stress leads to changes in the expression levels of schizophrenia-related genes and causes abnormal wiring of the neocortex.
We recently showed that increased expression of the neuroimmune gene complement component 4A (C4A) leads to decreased connectivity in pyramidal neurons of the prefrontal cortex and abnormal behavior in juvenile and adult mice (Comer et al. 2020).