Scholars@Duke
Michael Raphael Tadross

Michael Raphael Tadross

Assistant Professor in Neurosurgery
Neurosurgery

Selected Publications

Behavioral state and stimulus strength regulate the role of somatostatin interneurons in stabilizing network activity.

Journal Article Cell Rep · July 22, 2025 Inhibition stabilization enables cortical circuits to encode sensory signals across diverse contexts. Somatostatin-expressing (SST) interneurons are well suited for this role through their strong recurrent connectivity with excitatory pyramidal cells. We t ... Full text Link to item Cite

Ketamine rescues anhedonia by cell-type- and input-specific adaptations in the nucleus accumbens.

Journal Article Neuron · May 7, 2025 Ketamine is recognized as a rapid and sustained antidepressant, particularly for major depression unresponsive to conventional treatments. Anhedonia is a common symptom of depression for which ketamine is highly efficacious, but the underlying circuits and ... Full text Link to item Cite

DISENTANGLING 3D ANIMAL POSE DYNAMICS WITH SCRUBBED CONDITIONAL LATENT VARIABLES

Conference 13th International Conference on Learning Representations Iclr 2025 · January 1, 2025 Methods for tracking lab animal movements in unconstrained environments have become increasingly common and powerful tools for neuroscience. The prevailing hypothesis is that animal behavior in these environments comprises sequences of discrete stereotyped ... Cite

A one-step protocol to generate impermeable fluorescent HaloTag substrates for in situ live cell application and super-resolution imaging.

Journal Article bioRxiv · September 23, 2024 Communication between cells is largely orchestrated by proteins on the cell surface, which allow information transfer across the cell membrane. Super-resolution and single-molecule visualization of these proteins can be achieved by genetically grafting HTP ... Full text Link to item Cite

Natural phasic inhibition of dopamine neurons signals cognitive rigidity.

Journal Article bioRxiv · July 13, 2024 When animals unexpectedly fail, their dopamine neurons undergo phasic inhibition that canonically drives extinction learning-a cognitive-flexibility mechanism for discarding outdated strategies. However, the existing evidence equates natural and artificial ... Full text Link to item Cite

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

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 J Neural Eng · April 13, 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 millis ... Full text Link to item Cite

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

Journal Article Neuron · March 16, 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 receptor act ... Full text Link to item Cite

Noradrenergic Signaling Disengages Feedforward Transmission in the Nucleus Accumbens Shell.

Journal Article J Neurosci · April 28, 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 Link to item Cite

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

Journal Article ACS Chem Biol · October 19, 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 Link to item Cite

Deconstructing behavioral neuropharmacology with cellular specificity.

Journal Article Science · April 7, 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 Link to item Cite

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

Journal Article Science · February 19, 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 Link to item Cite

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

Journal Article Science · February 13, 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 Link to item Cite

Ca2+ channel nanodomains boost local Ca2+ amplitude.

Journal Article Proc Natl Acad Sci U S A · September 24, 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 Link to item Cite

Mouse model of Timothy syndrome recapitulates triad of autistic traits.

Journal Article Proc Natl Acad Sci U S A · September 13, 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 Link to item Cite

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

Journal Article J Gen Physiol · 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 Link to item Cite

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

Journal Article J Gen Physiol · 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 Link to item Cite

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

Journal Article J Microsc · 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 Link to item Cite

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

Journal Article Cell · June 27, 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 Link to item Cite

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

Journal Article Nature · February 14, 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 Link to item Cite