Understanding Circuits

PROJECT SUMMARY The precise assembly of neural circuits ensures accurate neurological function and behavior. For example, to communicate specific aspects of the visual world to the brain, retinal ganglion cells (RGCs) find and form synaptic contacts with specific postsynaptic partners out of the heterogeneous neuronal population of retino-recipient areas in the brain. One such area is the superior colliculus (SC), which receives direct retinal inputs and sends commands for direct innate behaviors such as escape or prey capture.

Project Summary/Abstract This proposal responds to an FOA (RFA-NS-18-030) calling for 1) “novel approaches to understand neural circuitry associated with well-defined social behaviors;” 2) Distributed circuits that contribute to the coordination of motivational states and reward behavior;” 3) “Empirical and analytical approaches to understand how behavioral states are emergent properties of the interaction of neurons, circuits and networks.” The study of subcortical circuits that control conserved, naturalistic behaviors is crucial to understanding brain function.

Project Summary Internal sodium balance is critical for many physiological functions, including osmoregulation and action potentials. Deciphering the mechanisms that control sodium intake is essential for understanding the principles of appetite regulation and sodium homeostasis in the body. Our understanding of central sodium appetite regulation is still lacking compared to other appetite circuits such as thirst and hunger. I propose to study this fundamental brain circuit that controls our internal ion balance using transcriptomic and molecular genetic tools.

Genetic and neural mechanisms underlying emerging social behavior in zebrafish Our goal is to understand emerging collective behaviors of groups, such as schooling and shoaling in fish. Our approach is to dissect basic sensorimotor transformations in the zebrafish, which we believe play a fundamental role in explaining emerging social interactions.

Project Summary A major limitation to understanding the brain is a shortage of technologies for tracking the activity of large populations of individual neurons across multiple layers of synaptic processing. Ideally, these measurements of population activity would be compatible with both optogenetic and chemogenetic manipulations of neural activity to test how targeted perturbations in signal processing alter the input-output relationship of the circuit.

PROJECT SUMMARY The SCid, a sensorimotor hub in the midbrain, plays a fundamental role in stimulus-guided behavior as well as spatial attention control. It encodes a topographic map of stimulus priority, i.e., of physical salience + behavioral relevance of stimuli, as well as a map of relative stimulus priority, which, together, form the basis of SCid's role in behavior. However, the contributions of intrinsic inhibitory cell types to the construction of the SCid's priority map and to behavior are not known.

Project Summary Spinal dorsal horn interneurons (IN) integrate somatosensory inputs and control their access to spinal projection neurons (PrN) that transmit nociceptive information to supraspinal components of pain pathways. The heterogeneity of dorsal horn neurons, limited knowledge on their connectivity, and lack of in vivo neurophysiological analysis of identified IN currently preclude comprehensive mapping of circuits involved in pain processing.

PROJECT SUMMARY It is widely thought that identifying how neurons are connected to each other in a brain circuit, its wiring diagram, is a necessary step towards understanding how brain activity gives rise to behavior, and how it is perturbed by disease. Unfortunately, currently available methods have limitations that make it challenging to visualize these brain wiring diagrams.

Abstract Vision is an active sense that we use to explore the world around us. However, studies of visual coding are generally performed in animals that are head-fixed, which constrains the range of visual functions and behaviors that are amenable to study, thereby excluding many ethologically relevant natural behaviors as well as the interaction of visual processing and movement.

The ability of our auditory systems to recognize target sounds in a mixture of other sounds is fundamental to normal healthy function and communication. For example, during the course of a normal day we must communicate with a conversation partner in the presence of other sounds, e.g., other people talking, music, sound of cars etc. Like humans, many animals are capable of listening to a single sound source in a mixture of sources. Thus, neural circuits for solving the CPP also likely exist in animals.