Scholars@Duke
Michael Raphael Tadross

Michael Raphael Tadross

Assistant Professor of Biomedical Engineering
Biomedical Engineering
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Selected Publications

DART.2: bidirectional synaptic pharmacology with thousandfold cellular specificity.

Journal Article Nat Methods · July 2024 Precision pharmacology aims to manipulate specific cellular interactions within complex tissues. In this pursuit, we introduce DART.2 (drug acutely restricted by tethering), a second-generation cell-specific pharmacology technology. The core advance is opt ... Full text Link to item Cite

Reward perseveration is shaped by GABA A -mediated dopamine pauses.

Journal Article bioRxiv · May 9, 2024 Extinction learning is an essential form of cognitive flexibility, which enables obsolete reward associations to be discarded. Its downregulation can lead to perseveration, a symptom seen in several neuropsychiatric disorders. This balance is regulated by ... Full text Link to item Cite

Local synaptic inhibition mediates cerebellar granule cell pattern separation and enables learned sensorimotor associations.

Journal Article Nat Neurosci · April 2024 The cerebellar cortex has a key role in generating predictive sensorimotor associations. To do so, the granule cell layer is thought to establish unique sensorimotor representations for learning. However, how this is achieved and how granule cell populatio ... Full text Link to item Cite

An open-source head-fixation and implant-protection system for mice.

Journal Article HardwareX · March 2023 Mice are widely used in neuroscience experiments, which often require head-fixation and attachment of skull-mounted hardware. For many experiments, these components must remain intact over weeks to months, ideally with animals group housed. Many labs have ... Full text Cite

An open-source transparent microelectrode array.

Journal Article Journal of neural engineering · April 2022 Objective.The micro-electrode array (MEA) is a cell-culture surface with integrated electrodes used for assays of electrically excitable cells and tissues. MEAs have been a workhorse in the study of neurons and myocytes, owing to the scalability and ... Full text Cite

Acute restraint stress redirects prefrontal cortex circuit function through mGlu5 receptor plasticity on somatostatin-expressing interneurons.

Journal Article Neuron · March 2022 Inhibitory interneurons orchestrate prefrontal cortex (PFC) activity, but we have a limited understanding of the molecular and experience-dependent mechanisms that regulate synaptic plasticity across PFC microcircuits. We discovered that mGlu5 r ... Full text Cite

Noradrenergic Signaling Disengages Feedforward Transmission in the Nucleus Accumbens Shell.

Journal Article The Journal of neuroscience : the official journal of the Society for Neuroscience · April 2021 The nucleus accumbens shell (NAcSh) receives extensive monoaminergic input from multiple midbrain structures. However, little is known how norepinephrine (NE) modulates NAc circuit dynamics. Using a dynamic electrophysiological approach with optogenetics, ... Full text Cite

Cell-Specific Chemical Delivery Using a Selective Nitroreductase-Nitroaryl Pair.

Journal Article ACS chemical biology · October 2018 The utility of small molecules to probe or perturb biological systems is limited by the lack of cell-specificity. "Masking" the activity of small molecules using a general chemical modification and "unmasking" it only within target cells overcomes this lim ... Full text Cite

Deconstructing behavioral neuropharmacology with cellular specificity.

Journal Article Science (New York, N.Y.) · April 2017 Featured Publication Behavior has molecular, cellular, and circuit determinants. However, because many proteins are broadly expressed, their acute manipulation within defined cells has been difficult. Here, we combined the speed and molecular specificity of pharmacology with t ... Full text Cite

Sequential ionic and conformational signaling by calcium channels drives neuronal gene expression.

Journal Article Science (New York, N.Y.) · February 2016 Voltage-gated CaV1.2 channels (L-type calcium channel α1C subunits) are critical mediators of transcription-dependent neural plasticity. Whether these channels signal via the influx of calcium ion (Ca(2+)), voltage-dependent conformational change (VΔC), or ... Full text Open Access Cite

Neural circuits. Labeling of active neural circuits in vivo with designed calcium integrators.

Journal Article Science (New York, N.Y.) · February 2015 The identification of active neurons and circuits in vivo is a fundamental challenge in understanding the neural basis of behavior. Genetically encoded calcium (Ca(2+)) indicators (GECIs) enable quantitative monitoring of cellular-resolution activity durin ... Full text Cite

Ca2+ channel nanodomains boost local Ca2+ amplitude.

Journal Article Proceedings of the National Academy of Sciences of the United States of America · September 2013 Local Ca(2+) signals through voltage-gated Ca(2+) channels (CaVs) drive synaptic transmission, neural plasticity, and cardiac contraction. Despite the importance of these events, the fundamental relationship between flux through a single CaV channel and th ... Full text Open Access Cite

Mouse model of Timothy syndrome recapitulates triad of autistic traits.

Journal Article Proceedings of the National Academy of Sciences of the United States of America · September 2011 Autism and autism spectrum disorder (ASD) typically arise from a mixture of environmental influences and multiple genetic alterations. In some rare cases, such as Timothy syndrome (TS), a specific mutation in a single gene can be sufficient to generate aut ... Full text Cite

Systematic mapping of the state dependence of voltage- and Ca2+-dependent inactivation using simple open-channel measurements.

Journal Article The Journal of general physiology · March 2010 The state from which channel inactivation occurs is both biologically and mechanistically critical. For example, preferential closed-state inactivation is potentiated in certain Ca(2+) channel splice variants, yielding an enhancement of inactivation during ... Full text Open Access Cite

Molecular endpoints of Ca2+/calmodulin- and voltage-dependent inactivation of Ca(v)1.3 channels.

Journal Article The Journal of general physiology · March 2010 Ca(2+)/calmodulin- and voltage-dependent inactivation (CDI and VDI) comprise vital prototypes of Ca(2+) channel modulation, rich with biological consequences. Although the events initiating CDI and VDI are known, their downstream mechanisms have eluded con ... Full text Open Access Cite

Robust approaches to quantitative ratiometric FRET imaging of CFP/YFP fluorophores under confocal microscopy.

Journal Article Journal of microscopy · January 2009 Ratiometric quantification of CFP/YFP FRET enables live-cell time-series detection of molecular interactions, without the need for acceptor photobleaching or specialized equipment for determining fluorescence lifetime. Although popular in widefield applica ... Full text Open Access Cite

Mechanism of local and global Ca2+ sensing by calmodulin in complex with a Ca2+ channel.

Journal Article Cell · June 2008 Calmodulin (CaM) in complex with Ca(2+) channels constitutes a prototype for Ca(2+) sensors that are intimately colocalized with Ca(2+) sources. The C-lobe of CaM senses local, large Ca(2+) oscillations due to Ca(2+) influx from the host channel, and the N ... Full text Open Access Cite

A modular switch for spatial Ca2+ selectivity in the calmodulin regulation of CaV channels.

Journal Article Nature · February 2008 Ca2+/calmodulin-dependent regulation of voltage-gated CaV1-2 Ca2+ channels shows extraordinary modes of spatial Ca2+ decoding and channel modulation, vital for many biological functions. A single calmodulin (CaM) molecule associates constitutively with the ... Full text Open Access Cite