24.05.18 (THURSDAY), 14.30-15.00: Cellular resolution circuit mapping in mouse models of autism with soma-targeted opsins (abstract here)
Dr. Bolton’s research is focused on understanding the alterations in neural circuits that underlie neuropsychiatric disorders such as schizophrenia and autism. Her lab combines a number of classic and recently developed techniques to test hypotheses regarding the contribution of specific neuron subtypes or inter-areal connections to circuit pathology. Whole cell patch clamp electrophysiology with quadruple simultaneous recording capability, semi-automated morphological reconstruction, stereotaxic surgery and behavioral analysis are the classic methods. In addition, they have developed a system for neural circuit mapping at single cell resolution using two-photon optogenetic excitation combined with imaging of genetically encoded calcium sensors to allow us to interrogate synaptic connectivity with unprecedented speed and accuracy.
Dr. Bolton was trained as an electrophysiologist by Donald Lo during her Ph.D. at Duke University, then added molecular biological and imaging techniques to her repertoire during her postdoctoral training with Michael Ehlers. Her career took a different path at this point when she was invited to join a biotech endeavor called Cogent Neuroscience started by her thesis advisor, Donald Lo and Laurence Katz, also from Duke. This experience and subsequent ventures in the drug discovery world, convinced her that well-coordinated applied research and drug screening efforts will change the lives of people suffering with mental illness and neurological disorders in her lifetime. But she recognized that the power of the drug discovery process can only be realized if it is based on a better understanding of the fundamental biology, and she returned to academic research with the goal of identifying specific neural circuit abnormalities that can be the basis for the rational development of effective drug targets for neuropsychiatric disorders.
Dr. Bolton is a council member of Brain Health Advisory Council and board member of National Alliance for Mental Illness Palm Beach County (NAMI).
Contribution to Science
- Fear generalization and altered amygdala circuitry in mouse models of Autism
B.Unal, C.T. Unal, C. A. Baker, M. Bolton (2015) Fear generalization in NLGN3R451C model of autism is associated with aberrant feedback inhibition in the lateral Amygdala. (In preparation)
- Development of a system for neural circuit mapping at single cell resolution using two-photon optogenetic excitation
Baker, C, Parra-Martin, A, Elyada, Y, and M. Bolton (2016) Cellular resolution circuit mapping with temporal-focused excitation of soma-targeted channelrhodopsin, eLife-14193.
- Cortico-striatal co-culture assay for Huntington’s Disease
Kaltenbach*, L.S., Bolton*, M.M., Shah, B., Turmel, G. J., Kanju, P.M., Lewis, G.M., Turmel, G. J., Trask, O. J. and D. C. Lo (2010) Composite Primary Neuronal High-Content Screening Assay for Huntington’s Disease Incorporating Non-Cell-Autonomous Interactions,Journal of Biomolecular Screening 15(7) 806-19.(*Equal contribution),
- Assay development for ion channel therapeutic targets
- Regulation of excitatory and inhibitory synaptic transmission by brain derived neurotrophic factor
Bolton, M.M., D.C. Lo, and N.T. Sherwood (2000) Regulation of excitatory and inhibitory synaptic transmission in hippocampal cultures by brain-derived neurotrophic factor. Prog. Brain Res., 128:203-218.
Bolton, M.M., A.J. Pittman, and D.C. Lo (2000) BDNF differentially regulates excitatory and inhibitory synaptic transmission in hippocampal neurons. J. Neurosci., 20: 3221-3232Up to 4 peer reviewed publications
URL to a full list of Dr. Bolton’s published work: