Research Interests

Why Non-Cholinergic Basal Forebrain Neurons? 

The basal forebrain (BF) has long been recognized as a critical center for arousal and attention. However, traditional research has focused almost exclusively on cholinergic neurons, even though they account for only a small fraction of the BF population. Instead, our lab focuses on noncholinergic neurons, which are anatomically prominent yet functionally underexplored and often neglected in the literature.

Specifically, we have identified a unique population of “BF bursting neurons” that exhibit precise, phasic responses to rewards and reward-predicting stimuli. We believe these neurons represent the missing link in understanding how the brain rapidly amplifies cortical processing in the presence of reward-predicting and therefore attention-deserving stimuli. Our central hypothesis is that BF bursting neurons are a special subset of GABAergic neurons that rapidly enhance corticothalamic activity through a disinhibition mechanism and serve as a global gain modulation mechanism. By broadcasting rapid signals to the cortex and thalamus, these neurons facilitate the detection of behaviorally relevant targets, thereby driving faster and more accurate decision-making.

Our current research is organized around four core questions:

1) How do basal forebrain (BF) bursting neurons shape selective attention and behavioral performance?

We ask whether BF bursting neurons act as a gain-control mechanism that selectively amplifies processing of behaviorally relevant stimuli. Using neural recordings and causal manipulations during attention tasks, we test how changes in BF bursting influence hit rate, reaction time, and the ability to sustain engagement. We also examine when this influence is strongest—especially during target identification—and whether the same circuit contributes to learning by promoting reward-seeking actions that accelerate the formation of new associations.

2) What inputs drive BF bursting—and does dopamine provide a key upstream signal?

We investigate how BF bursting neurons are recruited in real time and whether midbrain dopamine (DA) neurons provide a major excitatory input that triggers bursting. Using dual-site recordings and optogenetic perturbations, we test the timing and causal direction of DA–BF coupling, and determine whether DA input is necessary and/or sufficient for BF bursting during behavior. More broadly, we aim to understand how reward-prediction signals might be transformed into an attentional gain-control signal.

3) What is the molecular identity of BF bursting neurons—and how can we target them genetically?

A critical challenge is to define BF bursting neurons as a molecularly identifiable cell population. We use single-cell transcriptomic resources to identify candidate markers and validate them experimentally, enabling genetic access strategies to selectively record from and manipulate this population. These tools will support mechanistic tests of circuit function and provide a foundation for studying how the integrity of this cell type may be altered in disease-relevant contexts.

4) Where do BF bursting neurons act downstream to modulate brain-wide processing?

We ask how BF bursting neurons influence downstream circuits to enhance the signal-to-noise of attended information. Our working hypothesis is that BF outputs implement a disinhibitory “gating” mechanism within corticothalamic networks. We test this by mapping projections, recording downstream activity, and perturbing BF outputs while measuring changes in sensory representations and behavior.