Preprints

Acute in vivo proximity labeling for membrane targeted proteomics in neuronal circuits

Anguiano M, Zhang R, Robles M, Salemi MR, Phinney BS, Fenton EM, Leung CS, Lewis E, Lin S, Whistler JL, Nord AS, Kim CK. bioRxiv (2025). [full-text]

This study introduces membrane-targeted TurboID-based proximity labeling to capture short-timescale, subcellular proteomic changes in specific neuronal circuits of behaving mice, revealing projection-specific and cocaine-induced protein enrichment in the mPFC.

D3 dopamine receptors implicate a subtype of medium spiny neuron in the aversive effects of antipsychotic medications
Lewis E, Muir J, Li YC, Glienke J, Gooding SW, Bender KJ, Kim CK#, Whistler JL#. bioRxiv (2025). [full-text]

Second-generation antipsychotics can trigger aversive effects through D3 receptor–expressing NAc neurons, with quetiapine uniquely inducing tolerance by inhibiting these cells, revealing a cellular mechanism underlying SGA-related aversion and its selective adaptation..

Deconstruction of a memory engram reveals distinct ensembles recruited at learning
Pouget C, Morier F, Treiber N, García PF, Mazza N, Zhang R, Reeves I, Winston S, Brimble MA, Kim CK, Vetere G. bioRxiv (2024). [full-text]

Associative fear learning recruits distinct, non‑overlapping ensembles of dorsal CA1 neurons, each activated during specific moments of the acquisition experience. Using f-FLiCRE, with sub 5s temporal resolution, our collaborators shows that only certain stimulus‑linked ensembles form the core engram necessary for fear memory formation and recall.

2025

High-speed neural imaging with multiplexed miniature two-photon microscopy
Zhang Z*, Liu S-J*, Mattison*, Muir J, Spurr N, Kim CK, Yang W. Cell Reports Methods (2025). [full-text][pdf]

Our collaborators employed beam multiplexing with a miniaturized two‑photon microscope to dramatically increase imaging speed without losing spatial resolution. It further shows that this advance enables rapid 3D imaging and makes it possible to record fast voltage signals from large neuron populations in freely moving animals.

The psychoplastogen tabernanthalog induces neuroplasticity without proximate immediate early gene activation
Aarrestad IK*, Cameron LP*, Fenton EM, Casey AB, Rijsketic DR, Patel SD, Sambyal R, Johnson SB, Ly C, Viswanathan J, Barragan EV, Lozano SA, Seban N, Hu H, Powell NA, Chytil M, Meyer R, Rose D, Hempel C, Olson E, Hansen HD, Madsen CA, Knudsen GM, Redd C, Wheeler DG, Guanzon N, Muir J, Hennessey JJ, Quon G, McCorvy JD, Gandhi SP, Rasmussen K, Liston C, Gray JA, Heifets BD, Nord AS, Kim CK, Olson DE. Nature Neuroscience (2025). [full-text][PDF]

The nonhallucinogenic compound TBG increases cortical neuroplasticity through the same 5‑HT2A–TrkB–mTOR–AMPA receptor pathway used by classic psychedelics. This study shows that while TBG requires cortical spine growth to produce lasting antidepressant‑like effects, it does so without triggering the glutamate surge or immediate early gene activation typically associated with psychedelic‑induced plasticity.

2024

Isolation of psychedelic-responsive neurons underlying anxiolytic behavioral states
Muir J*, Lin S*, Aarrestad IK, Daniels HR, Ma J, Tian L, Olson DE, and Kim CK. Science (2024). [full-text][PDF][Nature News and Views][Nature Highlight][PNAS news][The Scientist][UCD news]

We found that a serotonergic psychedelic activates a distributed set of neurons in the mouse medial prefrontal cortex, spanning multiple cell types beyond those expressing 5‑HT2A receptors. Reactivating these tagged psychedelic‑responsive neurons reproduces the drug’s anxiolytic effects without triggering hallucinogenic‑like behaviors.

Neuromodulator and neuropeptide sensors and probes for precise circuit interrogation in vivo [review]
Muir J*, Anguiano M*, and Kim CK. Science (2024). [full-text][PDF]

Our review highlights new chemical biology tools that enable precise, real‑time control and measurement of specific neuromodulators and neuropeptides in awake animals. It shows how these tools uncover the distinct timescales and mechanisms by which these molecules shape learning, behavior, and neural circuit dynamics.

Rapid, biochemical tagging of cellular activity history in vivo
Zhang R*, Anguiano M*, Arrestad IK, Lin S, Chandra J, Vadde SS, Olson DE, and Kim CK. Nature Methods (2024). [full-text][PDF][bioRxiv][UCD news]

We engineered a fast, biochemical calcium‑dependent labeling system (CaST) that tags activated cells in vivo within minutes, without the need for implanted light sources. We further show that CaST reliably integrates calcium activity over time and can be used to identify psilocybin‑responsive neurons in freely behaving mice.

Machine learning ensemble directed engineering of genetically encoded fluorescent calcium indicators
Wait S, Expòsit M*, Lin S*, Rappleye M, Lee JD, Torp L, Ascensio A, Smith N, Regnier M, Moussavi-Harami F, Baker D, Kim CK, and Berndt A. Nature Computational Science (2024). [full-text][PDF]

This study shows that machine learning models trained on large GCaMP mutational datasets can accurately predict the functional effects of new sensor variants. This approach enabled the discovery of several improved GCaMP indicators—including eGCaMP, eGCaMP+, and eGCaMP2+—that outperform previous generations in speed, signal size, and dynamic range.

2023

Tagging neurons with light: Molecular circuits for activity-guided optogenetics [Science & PINS Prize runner-up essay]
Kim, CK. Science (2023). [full-text][PDF]

FLiCRE is a light‑ and calcium‑dependent tagging system that labels neurons activated during brief behavioral events in mice. Once these neurons are tagged with an opsin, they can be selectively reactivated later with light to reproduce the desired behavioral response.

Engineered allostery in light-regulated LOV-Turbo enables precise spatiotemporal control of proximity labeling in living cells
Li S-Y*, Cheah JS*, Zhao B, Xu C, Roh H, Kim CK, Cho KF, Udeshi ND, Carr SA, Ting AY. Nature Methods (2023). [full-text]

“The incorporation of light-responsive domains into engineered proteins has enabled control of protein localization, interactions and function with light. Through structure-guided screening and directed evolution, we installed the light-sensitive LOV domain into the proximity labeling enzyme TurboID to rapidly and reversibly control its labeling activity with low-power blue light. Overall, LOV-Turbo increases the spatial and temporal precision of proximity labeling, expanding the scope of experimental questions that can be addressed with proximity labeling.”

2022

Building synapses: using a synthetic approach to bridge synaptic membranes [commentary]
Kim CK, Kolodkin AL, Kang S, & Stuber GD. Building synapses: using a synthetic approach to bridge synaptic membranes. Faculty Reviews (2022). [full-text]

Correcting for the hemoglobin absorption artifact in fiber photometry data [preview]
Zhang R and Kim CK. Cell Reports Methods (2022). [full-text]

Before 2021

A molecular calcium integrator reveals a striatal cell type driving aversion
Kim CK*, Sanchez MI*, Hoerbelt P, Fenno LE, Deisseroth K, Ting AY. Cell (2020).

FLiCRE is a molecular tool that permanently tags cells experiencing brief calcium elevations, enabling minute‑scale recording of transient cellular activity into their transcriptome. It further shows that this stable tagging allows detailed characterization, manipulation, and reprogramming of specifically activated cell populations.

Luciferase-LOV BRET enables versatile and specific transcriptional readout of cellular protein-protein interactions
Kim CK, Cho KF, Kim MW, Ting AY. Elife (2019).

SPARK2 is a transcriptional reporter that activates only when a specific protein‑protein interaction coincides with luciferase‑driven activation of a light‑sensitive LOV domain. SPARK2 enables high‑throughput GPCR agonist screening and detection of cell–cell contacts with flexible genetic readouts.

Molecular tools for imaging and recording neuronal activity [review]
Wang W*, Kim CK*, Ting AY. Nature chemical biology (2019).

This review highlights how genetically encoded sensors are used to monitor different steps of neuronal activity, from action potentials to gene expression. It also describes current limitations of these tools and discusses future opportunities for developing more powerful molecular approaches to link brain activity with behavior.

Interacting neural ensembles in orbitofrontal cortex for social and feeding behavior
Jennings JH*, Kim CK*, Marshel JH*, Raffiee M, Ye L, Quirin S, Pak S, Ramakrishnan C, Deisseroth K. Nature (2019).

We showed that distinct neuronal subnetworks in the orbitofrontal cortex can be optically identified and precisely manipulated during reward‑related experiences. Activating these specific cell groups can bidirectionally control feeding behavior, including in contexts influenced by social factors.

A neural circuit mechanism for encoding aversive stimuli in the mesolimbic dopamine system
de Jong JW*, Afjei SA*, Pollock Dorocic I, Peck JR, Liu C, Kim CK, Tian L, Deisseroth K, Lammel S. Neuron (2019). 

Dopamine terminals in the ventral medial shell of the nucleus accumbens are uniquely excited by unexpected aversive events and their predictive cues, while dopamine terminals in other accumbens subregions show sustained inhibition. de Jong et al. reveal a subregion‑specific organization of VTA dopamine signaling for positive versus negative motivational stimuli.

Molecular and circuit-dynamical identification of top-down neural mechanisms for restraint of reward seeking
Kim CK*, Ye L*, Jennings JH, Pichamoorthy N, Tang DD, Yoo A-CW, Ramakrishnan C, Deisseroth K. Cell (2017).

A distinct subset of superficial mPFC neurons projecting to a specific nucleus accumbens subfield encodes whether to initiate or suppress reward‑seeking when punishment is possible. We show that this projection has unique molecular and circuit features, identifying a specialized pathway for regulating reward‑related decisions.

Rabies screen reveals GPe control of cocaine-triggered plasticity
Beier KT, Kim CK, Hoerbelt P, Hung LW, Heifets BD, DeLoach KE, Mosca TJ, Neuner S, Deisseroth K, Luo L, & Malenka RC. Nature (2017). 

These findings show that an unbiased rabies‑based mapping approach can identify experience‑driven changes in neural inputs without preselecting circuits. They reveal that cocaine increases activity in external globus pallidus neurons, leading to enhanced rabies labeling and uncovering previously unrecognized circuit elements that contribute to behavioral adaptation.

Modulation of prefrontal cortex excitation/inhibition balance rescues social behavior in CNTNAP2-deficient mice
Selimbeyoglu A, Kim CK, Inoue M, Lee SY, Hong ASO, Ramakrishnan C, Fenno LE, Davidson TJ, Wright M, & Deisseroth K. Science translational medicine (2017).

Acutely lowering the excitation–inhibition balance in the mPFC can rescue social behavior deficits in CNTNAP2‑knockout mice, a model of autism‑related phenotypes. PV‑neuron activity in the mPFC differs between knockout and wild‑type mice, suggesting that real‑time modulation of E:I balance can correct circuit‑level dysfunction underlying social impairments.

Integration of optogenetics with complementary methodologies in systems neuroscience [review]
Kim CK*, Adhikari A*, Deisseroth K. Nature Reviews Neuroscience (2017).

Modern optogenetics can now reproduce natural neural activity patterns thanks to its integration with electrophysiology, imaging, and structural and molecular mapping tools. This combined approach allows researchers to pinpoint the precise cells and circuits that causally drive physiology and behavior across a wide range of timescales and brain regions.

Simultaneous fast measurement of circuit dynamics at multiple sites across the mammalian brain
Kim CK*, Yang SJ*, Pichamoorthy N, Young NP, Kauvar I, Jennings JH, Lerner TN, Berndt A, Lee SY, Ramakrishnan C, Davidson TJ, Inoue M, Bito H, Deisseroth K. Nature Methods (2016).

Frame‑projected independent‑fiber photometry (FIP) enables simultaneous recording of activity from many defined brain regions and pathways in freely moving mice. FIP supports multi‑color recording and precise optical perturbations that reproduce natural activity patterns during behavior.

Projections from neocortex mediate top-down control of memory retrieval
Rajasethupathy P*, Sankaran S*, Marshel JH*, Kim CK, Berndt A, Lee SY, Jaffe A, Liston C, & Deisseroth K. Nature (2015).

These findings show that a previously unknown direct projection from the anterior cingulate cortex to the hippocampus exists in mice. They also show that optogenetically activating this AC→CA pathway can trigger contextual memory retrieval in virtual‑reality environments.

Extended field-of-view and increased-signal 3D holographic illumination with time-division multiplexing
Yang SJ, Allen WE, Kauvar I, Andalman AS, Young NP, Kim CK, Marshel JH, Wetzstein G, & Deisseroth K. Optics Express (2015). 

Combining galvanometer mirrors with sequential 3D holograms overcomes the field‑of‑view and power‑scaling limits of traditional SLM‑based two‑photon excitation. This approach expands the usable imaging volume and increases total signal, enabling improved 3D two‑photon calcium imaging in vivo.

Prolonged, brain-wide expression of nuclear-localized GCaMP3 for functional circuit mapping
Kim CK, Miri A, Leung L, Berndt A, Mourrain P, Tank DW, & Burdine RD. Frontiers in Neural Circuits (2014).

We generated transgenic zebrafish with strong, nucleus‑localized GCaMP3 expression throughout the brain up to at least 14 days post‑fertilization. This advance improves calcium‑signal resolution and enables brain‑wide expression of next‑generation indicators or other probes later into development, enhancing the utility of zebrafish for large‑scale neural circuit imaging.

Gating of neural error signals during motor learning
Kimpo RR*, Rinaldi JM*, Kim CK*, Payne HL*, & Raymond JL. eLife (2014).

The same climbing fibers can signal performance errors in both increasing and decreasing VOR gain, yet their ability to drive learning is not constant. Climbing fiber–induced plasticity is dynamically gated in vivo, even when error signals are strong, helping explain why such signals do not always result in motor learning.

Diverging neural pathways assemble a behavioural state from separable features in anxiety
Kim SY*, Adhikari A*, Lee SY, Marshel JH, Kim CK, Mallory CS, Lo M, Pak S, Mattis J, Lim BK, Malenka RC, Warden MR, Neve R, Tye KM, & Deisseroth K. Nature (2013).

Different subregions of the BNST have opposing effects on anxiety‑related behaviors. Specific projections from this single brain area can selectively control distinct features of the anxious state, revealing circuit mechanisms for how anxiety is assembled.