Our Research

• Excitation-inhibition dynamics and prefrontal interneuron function. A central focus of our lab is understanding how excitation and inhibition are dynamically coordinated within the medial prefrontal cortex (mPFC), a key region regulating mood, cognition, and stress adaptation. We study how distinct populations of GABAergic interneurons, particularly somatostatin (SST) and parvalbumin (PV) interneurons, interact with glutamatergic pyramidal neurons to shape network activity and behavior. A major question is how these interactions evolve over time following antidepressant treatment and how distinct phases of excitatory and inhibitory activity contribute to rapid versus sustained therapeutic responses.
• Fast-acting antidepressants and novel therapeutic strategies. How can we reproduce the remarkable therapeutic potential of rapid-acting antidepressants (e.g., ketamine) while developing safer and more targeted treatments? We study the mechanisms of action of ketamine and ketamine-related compounds, as well as drugs targeting GABA receptors, with particular emphasis on α5-containing GABA-A receptors. By defining how these treatments reorganize prefrontal network activity and synaptic function, we aim to identify mechanisms that can be leveraged to develop the next generation of fast-acting therapeutics.
• Opioid mechanisms: therapeutic actions versus behavioral liability. The contribution of the opioid system to ketamine's actions remains an important and unresolved question. Our research examines how opioid receptors and endogenous opioid signaling influence ketamine's effects within defined cortical neuronal populations and circuits. A major goal is to identify opioid-dependent mechanisms that support therapeutic responses while distinguishing them from pathways associated with reward and abuse liability, knowledge that could help preserve therapeutic efficacy while minimizing unwanted effects.
• Dopamine and neuromodulatory control of stress-related circuits. Dopamine provides a critical link between prefrontal function, motivation, cognition, behavioral adaptation, and reward. We study how dopaminergic signaling interacts with corticomesolimbic circuits, focusing on population-defined excitatory and inhibitory networks. By tracking these interactions during behavioral and pharmacological treatment, we aim to understand how dopamine contributes to the adaptive responses promoted by novel fast-acting antidepressants.
• Neural mechanisms of fear and anxiety. Fear learning and extinction provide powerful models for understanding how the brain forms, expresses, and updates responses to threat. We study how ion channels, neuronal activity, and rapid-acting antidepressants regulate specific neuronal populations and circuits controlling fear learning and extinction, with the goal of uncovering mechanisms relevant to anxiety and trauma-related disorders.

Approaches & Technologies

Our lab combines molecular neuropharmacology, genetics, systems neuroscience, and behavioral neuroscience to connect molecular mechanisms with neuronal activity, circuit function, and behavior. Our main approaches include:

• In vivo fiber photometry and neurotransmitter sensing – monitoring neuronal population activity and neurotransmitter dynamics in real time during defined behavioral epochs, including dual-color recordings and genetically encoded calcium and neurotransmitter sensors.
• Behavioral neuroscience – models and assays spanning stress, antidepressant- and anxiolytic responses, cognition, social behavior, motivation and reward, and fear learning and extinction.
• Chemogenetics and optogenetics – temporally precise, cell type- and circuit-specific manipulations to establish causal relationships between neuronal activity and behavior.
• Cell type- and circuit-specific genetic approaches – Cre-driver transgenic mouse lines, Cre/Flp-dependent viral strategies, shRNA-mediated gene knockdown, neuronal tagging, and intersectional approaches to manipulate molecular targets and functionally defined neuronal populations.
• Circuit mapping and neuronal tracing – viral and intersectional tracing strategies to define the inputs, outputs, and connectivity of specific neuronal populations and projection-defined circuits.
• Slice electrophysiology – measurements of neuronal excitability, synaptic transmission, and plasticity to determine how stress, pharmacological treatments, and genetic manipulations alter cellular and circuit function (in collaboration with the MacLean Lab).
• Molecular, synaptic, and structural analyses – activity mapping and neuronal tagging combined with molecular analyses and approaches to examine synaptic proteins, dendritic architecture, and dendritic spines.