Skip to main content
Nigel Bamford

Nigel Bamford, MD

Faculty Member

Center for Neurodevelopment and Plasticity

Email | Lab | Department | ORCID

Synaptic plasticity in movement disorders and addiction

The Bamford lab integrates fiber photometry, cyclic voltammetry, and electrophysiology in awake and behaving mice with optical experiments, whole-cell patch clamp recordings, and biochemical techniques in vitro to determine how alterations in dopamine availability modify the activity of cholinergic interneurons and spiny projection neurons within the striatum. We have demonstrated that dopamine and acetylcholine provide complex filtering of cortical information entering the striatum, and alterations in their availability can produce the signs and symptoms of many diseases. In animal models of dopamine deficiency, striatal filtering is impaired as residual dopamine more broadly inhibits release from cortical projections. Dopamine excess, as modeled by the repetitive use of psychostimulants, causes a chronic yet reversible depression in corticostriatal neurotransmission. During drug withdrawal, a psychostimulant challenge produces a paradoxical increase in glutamate release by activating cholinergic interneurons. These mechanisms extend to locomotor sensitization and drug intake escalation, both hallmarks of addiction. Huntington's mutation also produces biphasic age-dependent alterations in glutamate availability that alters corticostriatal pathway activation. Our efforts to understand striatal function have recently been improved by developing new genetic mouse models and optical techniques that allow focused stimulation of specific brain neurons in vitro and in vivo. One strategy is to genetically target acetylcholine transferase and tyrosine hydroxylase, key enzymes within the endogenous acetylcholine and dopamine synthesis pathways, respectively. We use the new Cre-loxP system with either viral gene transfer or genetic Cre-strains to manipulate acetylcholine and dopamine synthesis in selected neuronal populations or brain regions. These techniques provide a better understanding of the mechanisms by which dopamine modifies striatal activity. Because dopamine is important for emotion, motivation, learning, memory, and motor control, it may also be a prime candidate for mediating conscious behavior.




Nigel S. Bamford, MD, studied electrical engineering and medicine at the University of Utah. He trained in pediatrics, neurology, and child neurology at the Columbia College of Physicians and Surgeons and the Neurological Institute of New York. He started his career as a physician-scientist at the University of Washington in Seattle and moved to Yale in 2015 as the Section Chief of Pediatric Neurology. Nigel is the Director of the Pediatric Neurology Movement Disorders Program and Laboratory, caring for children with various neurological conditions. Nigel's wife, Lisa, is a dentist, and his son Ian is an analyst in corporate finance.