Skip to Main Content

Nigel S. Bamford, MD, FANA

Associate Professor of Pediatrics (Neurology) and Neurology
DownloadHi-Res Photo

Additional Titles

Associate Professor of Cellular and Molecular Physiology, Cellular & Molecular Physiology

Director, Pediatric Movement Disorders Clinic, Pediatrics

About

Titles

Associate Professor of Pediatrics (Neurology) and Neurology

Associate Professor of Cellular and Molecular Physiology, Cellular & Molecular Physiology; Director, Pediatric Movement Disorders Clinic, Pediatrics

Biography

Dr. Bamford is an Associate Professor in Pediatrics and Neurology. He attended medical school at the University of Utah and completed his residency at Columbia-Presbyterian Medical; Center, receiving specific training in general pediatrics and pediatric neurology at the Neurological Institute of New York and Columbia University. He received a professorship at Columbia University and later worked as a physician-scientist at Seattle Children’s Hospital and the University of Washington. After spending 13 years in Seattle, he moved to Connecticut in 2015, where he cares for children with neurological disease at Yale University School of Medicine. As Section Chief of Pediatric Neurology, Dr. Bamford oversees a growing and expanding division that is dedicated to serving the children of New England.

Dr. Bamford is an NIH-funded physician-scientist who spends time investigating the cause and treatment of neurological diseases in children. Dr. Bamford specializes in the treatment of children with movement disorders and uses novel optical techniques, electrophysiology, and behavioral experiments in the laboratory to determine how part of the brain called the basal ganglia, encodes normal learning and disturbances in movement. The basal ganglia represent a part of the brain that is involved in a number of debilitating neuropsychological diseases, including Tourette syndrome, tic disorder, Parkinsonism, Huntington disease, and substance dependence. He is examining the synaptic mechanisms that underlie these diseases and is evaluating pharmacological alternatives that will help improve treatment for those in need.

Appointments

Other Departments & Organizations

Education & Training

Postdoctoral Research Fellow
Movement Disorders Section, Neurological Institute (2002)
Resident, Pediatric Neurology
Neurological Institute (1997)
Resident, Pediatrics
Columbia-Presbyterian Medical Center (1994)
Intern, Pediatrics
Columbia-Presbyterian Medical Center (1993)
Medical Student
University of Utah School of Medicine (1992)
MD
University of Utah, School of Medicine (1992)
BS
University of Utah, Electrical Engineering (1988)
AS
Salt Lake Community College, Electronic Technology (1984)

Research

Overview

Dr. Bamford has a strong track record of research funding, ranging from private grants to NIH. Dr. Bamford’s laboratory investigations focus on the function of the mammalian corticostriatal system. This system includes a collection of neurons that connect the cerebral cortex and striatum. The striatum plays an essential role in cognition, motor control, cue-dependent behaviors and abnormal function underlies aspects of numerous developmental, neurological, and psychiatric disorders, including Tourette syndrome, attention deficit–hyperactivity disorder, substance abuse, Parkinson’s disease, and Huntington’s disease. New treatments are needed and Bamford’s investigations offer critical insights into novel treatment options. In these disorders, too much or too little dopamine alters striatal excitation, resulting in clinical symptoms. To gain insight into synaptic plasticity induced by alterations in dopamine availability, the Bamford Lab combines behavioral investigations with optical, electrophysiological, biochemical, and immunohistochemical methods to determine the mechanisms underlying striatal modulation of glutamate release by dopamine, GABA, endocannabinoids, adenosine, and acetylcholine.

Since establishing his laboratory at the University of Washington in 2002, Dr. Bamford has published exceptional papers in Neuron, the Journal of Neuroscience, the Journal of Physiology, Annals of Neurology, and Nature Neuroscience. His work utilizes a novel technique, developed by Bamford and David Sulzer at Columbia University, which allows direct optical visualization of presynaptic cortical terminals in the striatum. This technique provides a robust way to measure kinetics of glutamate release from individual synaptic terminals. Investigations demonstrate that glutamate release from cortical projections in the motor striatum is directly regulated by dopamine, adenosine, and endocannabinoids. By regulating a subset of terminals, dopamine and these other neuromodulators alter the parallel processing of cortical inputs to the striatum, affecting striatal filtering of cortical information that leads to specific behaviors in mice (Neuron, 2004). Using dopamine-deficient mice and dopamine depleted mice, Bamford demonstrated that dopamine is not required during development for functional dopamine receptors. Dopamine depletion results in hypersensitive dopamine receptors that result in aberrant striatal function resulting in motor dyskinesias (Journal of Neuroscience, 2004).

Dopamine excess, as modeled by repeated use of the psychostimulants amphetamine and methamphetamine, produces a chronic striatal depression that is renormalized by drug reinstatement. This effect is dose dependent, long lasting (>140 days) and is dependent on a new D1 receptor effect seen only in animals with previous psychostimulant experience.During withdrawal, a psychostimulant challenge produces a paradoxical increase in glutamate release. This increase in glutamate from suppressed terminals correlates with locomotor sensitization and the model extends to drug intake escalation, both hallmarks of addiction (Neuron, 2008). These findings received wide press coverage and included reports on BBC National and World Radio, ABC, Washington Post, Science and Nature, New Scientist, and Scientific American.

In other studies, Bamford and co-workers found that the huntingtin mutation produces age-dependent alterations in corticostriatal activity that is paralleled by a decrease in dopamine D2 receptor modulation of the presynaptic terminal. Taken together, these findings point to dynamic alterations in the corticostriatal pathway and emphasize that therapies directed toward alleviating or preventing symptoms need to be specifically designed depending on the progression of the disorder (Journal of Neuroscience, 2008).

More recently, the Bamford lab showed how dopamine, endocannabinoids, and adenosine modulate frontal cortical projections to the nucleus accumbens (Journal of Physiology, 2012). In this study, workers combined optical recordings of presynaptic release with whole-cell electrophysiology in CB1 receptor-null mice and bacterial artificial chromosome (BAC) transgenic mice

Bamford also published a important article describing the behavioral effects of prenatal cocaine exposure (PCE) and the synaptic and biochemical mechanisms that might account for those behaviors (Annals of Neurology, 2013). PCE remains a serious health problem and can produce significant developmental and motor disabilities in affected humans. Observations in the clinic and laboratory strongly suggest that PCE causes corticostriatal dysfunction, but this important pathway has never been investigated. In this manuscript, Bamford and co-workers used a murine model for PCE to characterize abnormal dopamine-dependent behaviors and synaptic plasticity of the corticostriatal pathway. They found that PCE reduces body growth and modifies dopamine-dependent motor behaviors in adolescent mice. Abnormal motor-learning and blunted locomotor responses to repeated amphetamine were paralleled by a reversible GABA-dependent over-inhibition at corticostriatal synapses and a reduction in phasic dopamine release capacity. The release of dopamine promoted normal corticostriatal filtering in controls, but alleviated GABA-mediated inhibition and paradoxically increased corticostriatal activity in those mice with a history of PCE. While GABAA receptors had no effect on presynaptic corticostriatal activity in controls, their inhibition normalized synaptic function following PCE and prevented D2 receptor-dependent paradoxical presynaptic potentiation suggesting new therapeutic approaches for behaviors that follow PCE.

The Bamford laboratory has collaborated extensively with the Palmiter laboratory at the University of Washington on a number of projects. We showed that amphetamine sensitization requires balanced NMDA receptor activity in dopamine D1 and D2 receptor-expressing medium spiny neurons (PNAS, 2011) and that attenuating GABAA receptor signaling in dopamine neurons selectively enhances reward learning and alters risk preference in mice (Journal of Neuroscience, 2011). In another paper published in Nature Neuroscience (2012), we showed that the orphan G-protein-coupled receptor GPR88 is robustly expressed in medium spiny neurons in the striatum and regulated by neuro-pharmacological drugs. In the absence of GPR88, medium spiny neurons have increased glutamatergic excitation and reduced GABAergic inhibition that together promote enhanced firing rates in vivo, resulting in hyperactivity, poor motor-coordination, and impaired cue-based learning in mice. Targeted viral expression of GPR88 in medium spiny neurons rescues the molecular and electrophysiological properties and normalizes behavior, suggesting that aberrant medium spiny neurons activation in the absence of GPR88 underlies behavioral deficits and its dysfunction may contribute to behaviors observed in neuropsychiatric disease.

Dr. Bamford’s study published in the Journal of Neuroscience (2013) shows how acetylcholine encodes long-lasting presynaptic plasticity at glutamatergic synapses in the dorsal striatum after repeated amphetamine. Locomotion and cue-dependent behaviors are modified through corticostriatal signaling, where short-term increases in dopamine availability can provoke persistent changes in glutamate release that contribute to neuropsychiatric disorders including Parkinson’s disease and drug dependence. He showed that withdrawal of mice from repeated amphetamine treatment caused a chronic presynaptic depression (CPD) in glutamate release that was most pronounced in corticostriatal terminals with a low probability of release and lasted more than 50 days in treated mice. An amphetamine challenge reversed CPD, via a dopamine D1-receptor-dependent paradoxical presynaptic potentiation (PPP) that increased corticostriatal activity in direct pathway medium spiny neurons. This PPP correlated with locomotor responses following a drug challenge, suggesting that it may underlie the sensitization process. Experiments in slices and in vivo indicated that dopamine regulation of acetylcholine release from tonically active interneurons (TANs) contributes to CPD, PPP, locomotor sensitization, and cognitive ability. Thus, a chronic decrease in corticostriatal activity during withdrawal is regulated around a new physiological range by TANs and returns to normal upon re-exposure to amphetamine, suggesting that this paradoxical return of striatal activity to a more stable, normalized state may represent an additional source of drug motivation during abstinence.

The Bamford laboratory is currently supported by the NIH: Dopamine-Induced Striatal Synaptic Plasticity (2R01NS060803-07).

Medical Subject Headings (MeSH)

Ataxia; Chorea; Dystonia; Motor Skills; Movement Disorders; Neurology; Parkinsonian Disorders; Pediatrics; Tourette Syndrome; Tremor

Research at a Glance

Yale Co-Authors

Frequent collaborators of Nigel S. Bamford's published research.

Publications

2023

2022

2021

2020

Clinical Trials

Current Trials

Academic Achievements & Community Involvement

  • activity

    Society for Neuroscience

  • activity

    Child Neurology Society

  • activity

    American Academy of Neurology

  • activity

    Catecholamine Club

  • activity

    American Academy of Neurology, Movement Disorders Section

Clinical Care

Overview

Nigel Bamford, MD, is a pediatric neurologist who treats children with movement disorders. As the director of the Pediatric Movement Disorders Clinic at Yale, he aims to integrate pediatric neurology, pediatric neurosurgery, genetics and psychology into the care of children with abnormal motor function. Thanks to progressing research, the knowledge base of movement disorders is quickly advancing, and Dr. Bamford is often able to tell patients “we have seen this before and have good treatments that will help your child.”

An associate professor of pediatrics and neurology and is the chief of pediatric neurology at Yale School of Medicine, Dr. Bamford is also an active neuroscientist who has done groundbreaking research on the mechanisms underlying motor learning, habit formation and movement disorders. Being a physician-scientist is a clear advantage, he says. “The overlap between studies in basic neuroscience and clinical medicine is providing new insights and generating novel, successful treatments that help children live happy lives.”

One of Dr. Bamford’s special interests within pediatric neurology is the diagnosis and treatment of paroxysmal dyskinesias, an uncommon disorder characterized by intermittent excessive and abnormal movements. “I have seen many children with this disorder and careful and directed treatment can reduce or eliminate the abnormal movements and improve their lives,” he says. Dr. Bamford, who identified a particular brain cell that causes these movements, heads a federally funded lab that is investigating brain pathways and novel treatments for dyskinesias.

Clinical Specialties

Pediatrics; Pediatric Neurology; Movement Disorders

Fact Sheets

Board Certifications

  • Neurology with Special Qual in Child Neurology

    Certification Organization
    AB of Psychiatry & Neurology
    Latest Certification Date
    2020
    Original Certification Date
    2000

Yale Medicine News

Get In Touch

Contacts

Academic Office Number
Appointment Number
Office Fax Number

Administrative Support

Locations

  • Patient Care Locations

    Are You a Patient? View this doctor's clinical profile on the Yale Medicine website for information about the services we offer and making an appointment.