Research
What big question does the Schroeder lab aim to address?
The way that we feel has a profound influence over our behavior.
What big question does the Schroeder lab aim to address?
The way that we feel has a profound influence over our behavior. Emotions like fear or motivations like curiosity can prompt us to flee from danger or to explore, while physiological needs such as hunger or fatigue might cause us to conserve energy by reducing movement.
Yet, our responses are highly adaptable; in different environments, we might hide or fight when afraid, forage, or rest when hungry, showing that our behaviors are flexible and shaped by both internal states and the external context.
Despite the critical importance of these computations for survival, we know surprisingly little about where in the brain they occur or how the brain achieves them. The goal of the Schroeder lab is to investigate how the brain generates internal states and then uses this vital information, along with external sensory cues and learned information from past experiences, to adapt behavior in dynamic environments.
In particular, our lab studies how emotions, motivations, and needs are processed in the subthalamic circuits of the mysterious zona incerta, an emerging hub that regulates an impressive range of behaviors. In parallel, we aim to develop new therapeutic directions for psychiatric disease via neuromodulation. To achieve these goals, we use cutting-edge molecular, cellular, and circuit-level technologies in mouse models, along with diverse behavioral paradigms and advanced machine-learning techniques.
In which models and brain areas do we investigate?
Mice exhibit a range of complex behaviors and can adapt to various environmental challenges, making them a powerful and versatile model for studying neural circuits and behavior.
In which models and brain areas do we investigate?
Mice exhibit a range of complex behaviors and can adapt to various environmental challenges, making them a powerful and versatile model for studying neural circuits and behavior.
Their extensive genetic, neuroanatomical, and functional similarities to humans additionally enhance their relevance in translational research, allowing findings to be more effectively applied to human biology and disease, which is one of the ultimate goals of our lab.
In the mouse brain, we focus on the zona incerta, a subthalamic nucleus which, as its name suggests, remains one of the brain’s least studied regions. The zona incerta is highly heterogeneous but is mostly composed of long-range inhibitory neurons that have widespread connections across the neuroaxis. In addition to integrating sensory inputs across modalities, mounting evidence from our lab and others suggests that the zona incerta is a critical node for internal state processing, which encodes experience-dependent information and operates as a central switchboard for adaptive behavior.
What is an internal state, and how does this relate to feelings?
Internal states refer to the physiological and psychological conditions within an organism that reflect their current status, mood or drive.
What is an internal state, and how does this relate to feelings?
Internal states refer to the physiological and psychological conditions within an organism that reflect their current status, mood or drive.
These include emotions (e.g., fear, happiness), physiological needs (e.g., hunger, thirst), motivations (e.g., curiosity, sexual arousal) and regulatory states (e.g., fatigue, pain, stress). Dynamic in nature, these states profoundly influence perception and decision-making, enabling organisms to regulate and optimize their behavior based on the body’s needs and environmental demands.
Nearly all psychiatric and neurological disorders involve disruptions in internal state representations. Symptoms include mood disturbances, altered arousal and stress responses, disrupted sleep, changes in appetite, fluctuations in energy levels, and altered pain perception. These disruptions, as seen in conditions like anxiety disorders, depression, eating disorders, and Parkinson’s disease, significantly impact behavior and quality of life.
Objective measurements of biological indicators, such as changes in neural activity, hormone levels, or behavior, allow us to infer internal states. This contrasts with feelings, which are the subjective, conscious, and inherently personal experiences arising from these internal states. Studying internal states, therefore, allows us to gain objective insights into the physiological and neural mechanisms that may contribute to the subjective experience of feelings.
Tools & techniques
We address these questions using cutting-edge molecular, cellular, and circuit-level approaches in the mouse brain, such as single-cell RNA-sequencing, whole-cell patch-clamp electrophysiology, viral circuit tracing, optogenetics and in vivo calcium imaging via Miniscopes or two-photon microscopy.
This is combined with diverse behavioral paradigms and rich readouts of internal states, which we analyze using advanced machine learning and computer vision techniques.
In vivo calcium imaging
Molecular profiling
Circuit mapping & manipulation
