Research

 

In our laboratory, we address two main questions:

  1. How does the brain influence our motivation to respond to physiological needs?
  2. How does the brain sense, process, and prioritize sensory information to guide behavior?

We are interested in deconstructing the neural circuits that underlie the behavioral response to physiological needs in order to better understand how the brain guides behavior in a complex environment. We focus our efforts on essential behaviors – such as food seeking and ingestion – as these robust responses are evolutionarily conserved and amenable for examination in murine models. Maladaptive responses to such basic survival signals lead to improper decisions and have consequences for human health, including metabolic and affective disorders. By understanding the neural coding of adaptive survival behaviors, we aim to establish the framework to understand the dysfunction underlying these disorders.

Understanding how information coding nutrient deficit is integrated in the brain:

Starvation sensitive Agouti Related Peptide (AGRP) neurons are activated by hunger and provide an entry point to the neural circuitry that influences food seeking and consumption. Similar to the way sensory neurons responding to odorant or light have served as an entry point to understanding the processes of olfactory or visual information, we are exploring how nutrient-sensing neurons signal the rest of the brain to influence consumption of food.

Figure1

Figure 1. Structure-function relationship of the AGRP neuron system.

 The diagram reveals the anatomical configurations of AGRP neurons. Independent subpopulations of AGRP neurons project to only one target region. Projections to target regions in blue are sufficient to elicit feeding.

How do individual projections motivate food seeking and consumption? We are interested in understanding how these distinct projections influence the behavioral response to hunger.

 

Figure2

Figure 2. Neural diversity in AGRP target regions.

AGRP neurons innervate regions of the brain with molecularly distinct neural subtypes. Example above reveals non-overlapping populations of neurons expressing different neuropeptides. 

To better understand how AGRP neurons form circuits, we are exploring the neural cell types modulated by activity in hunger-sensing neurons.

Exploring how hunger influences our perception of and response to other environmental stimuli:

We know that food seeking and consumption do not occur in isolation. Ethological experiments performed across the spectrum of chordates reveal that internal sensory cues such as hunger induce cognitive changes that are known to influence the perception of and response to other survival stimuli.

figure3

Figure 3. Ethological behavioral influence of hunger

 

 

 

 

For example, how does an animal know when to seek food or when to hide from a potential predator? We approach this problem by mapping and manipulating the circuit intersection between neurons responsive to distinct and often conflicting needs. The balance between these activities is finely tuned and shifting this equilibrium underlies pathological conditions.

Our hope is that by better understanding how different survival needs interact, we will establish a framework for revealing how the brain processes conflicting stimuli to guide behavior.