Epigenetic Mechanisms Linking Cerebral Cortical Cell Types to Gene Expression and Connectivity

2017 Scientific Innovations Award
Edward Callaway, Ph.D.
Systems Neurobiology Laboratories
The Salk Institute for Biological Studies

Brain circuits develop through an interaction between genetics and the environment. Previous studies have shown that there are at least two distinct phases in brain development. During a first genetically determined stage, gene expression dictates the emergence of cell types and their specific connections to establish a basic scaffold. Sensory experience and interactions with the environment then further shape and refine these connections. Nevertheless, the postnatal or adolescent onset of brain circuit disorders including schizophrenia and autism that have predisposing genetic factors, argue that there is in fact a more complex and intimate interplay between genetics and the environment. Here we propose to test hypotheses emerging from recent observations suggesting specific brain circuits and epigenetic mechanisms that might be involved in these processes. These foundational studies would provide a framework for detailed investigations of the underlying mechanisms and how they can go wrong in neurodevelopmental disorders.

Other Awards

Angelique Bordey, Ph.D., Yale University
The Role of Ribosomes in Synaptic Circuit Formation and Socio-Communicative Deficits
Our proposal aims at identifying a molecular mechanism responsible for autism-like socio-communicative defects in the developmental disorder, tuberous sclerosis complex (TSC). TSC is a genetic disorder with a 30-60% incidence…
Adam E. Cohen, Ph.D., Harvard University
To spike or not to spike? Mapping dendritic computations in vivo.
The brain is made of neurons, and neurons convert synaptic inputs to spiking outputs. How does a neuron decide when to spike?
Gina Turrigiano, Ph.D., Brandeis University
Homeostatic Maintenance of Neocortical Excitation-inhibition Balance by Ciliary Neuropeptidergic Signaling
Brain circuit wiring is adjusted during adolescence to generate fully functional circuits, and this process depends on an interaction between genetics and experience. During this period of experience-dependent development, excitatory…
Gregory Scherrer, Ph.D., The University of North Carolina at Chapel Hill
Mechanisms of Affective States and Drug Discovery at the Intersection of Chronic Pain and Opioid Addiction
Pain is normally a sensation that we experience when our body is exposed to damaging stimuli, such as the noxious heat of an open flame. However, when chronic, pain becomes…