Balancing Neuronal Excitation and Inhibition for Functional Behaviors

The Dallman lab uses the zebrafish Danio rerio, as a model to understand the development of neuronal circuits that produce rhythmic motor behaviors like swimming, and how the development of these neuronal circuits is affected by genetic or environmental perturbation. 

Glial glycine transporter (GlyT1) mutant:

In the GlyT1 mutant shocked, developmental onset of swimming is disrupted by nervous system accumulation of the inhibitory neurotransmitter glycine.  Elevated glycine inhibits motor neurons from firing action potentials, effectively paralyzing GlyT1 mutant embryos.  As embryos continue to develop however, they gradually recover the ability to swim even though nervous system glycine remains high.  We study the sequential compensatory mechanisms that enable normal swimming despite build up of inhibitory glycine. Our lab uses electrophysiology, immunohistochemistry and live imaging to study these underlying mechanisms of recovery.

Modeling Human Hyperekplexia:

In collaboration with Professor Harvey at the School of Pharmacy in London we use zebrafish to model the vertebrate startle disease Hyperekplexia.  Hyperekplexia is caused by mutations in genes that reduce the strength of glycinergic synapses, so that when animals are startled, excessive nervous system excitation causes temporary cessation of breathing and severe muscle stiffness.  Mutations that cause this disease have been found in cows, dogs, and humans but, because these animals develop in utero, none provide access to the question of how disrupting genes that reduce glycinergic signaling impact the development of neuronal circuits.  We address this questions in zebrafish.

Sensitivity to Anesthetics:

General anesthetics are both highly prized and widely applied for their ability to produce transient periods of immobility, loss of conscious, and absence of pain that facilitate often life-saving invasive procedures.  Unfortunately, genetically inherited diseases can put a patient at risk for anesthesia.  While these patients are easily anesthetized, they do not readily recover after removal of anesthesia.  To understand underlying mechanisms, we model anesthetic sensitivity in the zebrafish GlyT1 mutant.