Neuromodulatory mechanisms and molecular tool development
Research in the Banghart lab involves two intertwined themes: neuromodulatory mechanisms and molecular tool development.
Several questions of interest include:
- How do neuromodulators transform neural circuit function?
- What principles determine the spatial and temporal domains of neuromodulatory signaling?
- When and where are neuromodulators released in the brain?
- How are neuromodulatory pathways compromised in disease and how can they be restored?
We address these questions in the mammalian basal ganglia, a collection of neural circuits that rely heavily on neuromodulators to mediate decision-making, goal-oriented movements and behavioral reinforcement. Our experimental approach utilizes contemporary genetically-targeted neuroanatomical methods, whole-cell electrophysiology, two-photon imaging and rodent behavioral analysis, often in conjunction with optogenetic and chemical-genetic perturbations. To facilitate these efforts, we develop novel molecular tools for observing and manipulating neuromodulatory activity with an emphasis on photoactivatable (or caged) neurotransmitters, optical sensors and genetically-targeted pharmacological probes.
Banghart MR, Neufeld SQ, Mulder N, Sabatini BL. Enkephalin disinhibits mu-receptor rich striatal patches via delta opioid receptors. Neuron (2015), 88(6), 1227-39. PMID 22671460
Olson J, Banghart MR, Sabatini BL, Ellis-Davies GCR. Spectral evolution of a photochemical protecting group for orthogonal two-color uncaging with visible light. Journal of the American Chemical Society (2013), 135(42), 15948-54. PMID 24117060
Banghart MR, Williams JT, Shah RC, Lavis LD, Sabatini BL. Caged naloxone reveals opioid signaling deactivation kinetics. Molecular Pharmacology (2013), 84(5), 687-95. PMID 23960100
Banghart MR, Sabatini BL. Photoactivatable neuropeptides for spatiotemporally precise delivery of opioids in neural tissue. Neuron (2012), 73, 249-59. PMID 22284180
Tochitsky I, Banghart MR, Mourot A, Yao JZ, Gaub B, Kramer RH, Trauner D. Optical control of genetically engineered neuronal nicotinic acetylcholine receptors. Nature Chemistry (2012), 4(2), 105-11. PMID 22270644
Dvir T, Banghart MR, Timko BP, Langer R, Kohane DS. Photo-targeted nanoparticles. Nano Letters (2010), 10 (1), 250-254. PMID 19904979
Banghart MR, Mourot A, Fortin DL, Yao JZ, Kramer RH, Trauner D. Photochromic blockers of voltage-gated potassium channels. Angewandte Chemie International Edition (2009), 48 (48), 9097-9101. PMID 19882609 Fortin DL, Banghart MR, Dunn TW, Borges K, Wagenaar DA, Gaudry Q, Karakossian MH, Otis TS, Kristan WB, Trauner D, Kramer RH. Photochemical control of endogenous ion channels and cellular excitability. Nature Methods (2008), 5(4), 331-338. PMID 18311146
Banghart MR, Volgraf M, Trauner D. Engineering light gated ion channels. Biochemistry (2006), 45(51), 15129-15141. PMID 17176035
Banghart M, Borges K, Isacoff E, Trauner D, Kramer RH. Light-activated ion channels for remote control of neuronal firing. Nature Neuroscience (2004), 7(12), 1381-1386. PMID 15558062
Miller AK, Banghart MR, Beaudry CM, Suh JM, Trauner D. Development of novel Lewis acid catalyzed cycloisomerizations: synthesis of bicyclo[3.1.0]hexenes and cyclopentenones. Tetrahedron (2003), 59(45), 8919-8930.