Laboratory of Neuroscience at VA Boston Healthcare System

Department of Psychiatry, Harvard Medical School
Directors: Radhika Basheer, Ph.D., Robert Strecker, Ph.D., Ritchie E. Brown, Dr. Rer. Nat.

The Laboratory of Neuroscience, at the West Roxbury Division of the VA Boston Healthcare System (VABHS), was founded by pioneering sleep researcher, Robert W. McCarley, who passed away in 2017. Its current directors are Radhika Basheer, Robert Strecker and Ritchie E. Brown, Full Preceptors on the T32 Training Program in Sleep, Circadian and Respiratory Neurobiology. These investigators work closely with other funded scientists at the Assistant Professor/Instructor level, James McKenna (Assistant Professor), James McNally (Assistant Professor, Associate Preceptor on T32), Dmitry Gerashchenko (Assistant Professor), Mark Zielinski (Assistant Professor), David Uygun (Instructor), Fumi Katsuki (Instructor) and Felipe Schiffino (Instructor). Funding is provided by grants from the US Veterans Administration, National Institutes of Health, and industry.

The Laboratory of Neuroscience at VABHS is a multidisciplinary, highly collaborative laboratory devoted to the understanding of brain mechanisms controlling sleep and their dysfunction. Techniques include neuroanatomy, whole-cell patch-clamp recordings, molecular biology, in vivo electrophysiology, spectral analysis, optogenetics, chemogenetics, fiber photometry, CRISPR gene editing and behavioral analysis in genetically modified mice. These techniques are used to conduct preclinical basic research focusing on key questions related to sleep and wakefulness:

1) Which brain mechanisms make us sleepy when we stay awake for prolonged periods?

2) What is the role of different brain neurons in waking us up, putting us to sleep and switching between different states of sleep and how can we identify and target them?

3) What cellular and neurobehavioral changes are associated with sleep loss/disruption and how can we overcome them?

4) How do brain arousal and sleep mechanisms go awry in schizophrenia?

5) How do hypnotic drugs act, how can we improve them and how can we use them to treat sleep disorders such as insomnia?

6) Can we manipulate brain oscillations typical of arousal or sleep to improve cognition, counteract sleep deprivation and promote optimal brain health?

7) How does the immune system control sleep?

8) How can we use knowledge of arousal and sleep mechanisms to improve brain function in mouse models of human diseases and in aging?

ACTIVE GRANTS
NIH:
R01 NS119227 Neural correlates of sleep homeostasis (PI: Radhika Basheer)
RF1 AG061774 Slow-wave activity as a modifier of the progression of neurodegeneration in Alzheimer's disease
(PI: Dmitry Gerashchenko)
R21 MH125242 Subcortical influence on the respiratory coordination of cortical neurodynamics related to cognition. (PI: James T. McKenna; Co-PI: James M. McNally)
K01 AG068366 Alteration of sleep and cortical parvalbumin interneurons in mouse model of Alzheimer’s disease
(PI: Fumi Katsuki)
K99 AG066819 Controlling oscillations to treat Alzheimer’s disease targeting the basal forebrain parvalbumin system (PI: Felipe Schiffino)

VA:
VA Merit Review I01 BX001404 Purinergic Mechanisms in Homeostatic Sleep Control (PI: Radhika Basheer)
VA Merit Review I01 BX004673 & Mentored Research Supplements to Promote Diversity. Specification of sleep-wake control neurons in the basal forebrain (PI: Ritchie E. Brown)
VA Merit Review I01 BX002774 Role of the basal forebrain in sleep loss induced attention impairments (PI: Robert Strecker)
VA Merit Review I01 BX004500 Tuning cortical E/I balance for translational modeling of psychiatric disorders (PI: James McNally)
VA Career development Award (CDA2) IK2 BX004905 Using CRISPR-Cas9 genetic abscission in vivo to study the role of GABA-A receptors of the thalamic reticular nucleus in regulating non-rapid-eye-movement sleep and drug induced sleep (PI: David Uygun)
VA summer research program grant for undergraduates to enhance the diversity of the VA workforce in biomedical research. “Diversity in Research Training at VABHS” (PD: Robert Strecker, co-PD: John McCoy)

Industry:
Merck Investigator Studies Program (PI: McKenna, Co-PI: Strecker)