Research Projects

Summary Neuroscience has an essential requirement for large-scale perturbation tools. Such tools would be transformative in the mapping of brain function, the causal testing of neurotheoretic models, and the diagnosis and treatment of neurological disorders. The proposed five-year project is aimed at uncovering the fundamental mechanisms of US stimulation through the reciprocity of mathematical analysis, computational modeling and experimental validation.

Abstract Magnetogenetics is a recently proposed method for stimulating cells using electromagnetic fields. In one approach, radio-frequency (RF) electromagnetic fields are applied to stimulate membrane channel proteins such as TRPV1 and TRPV4 that are attached to ferritins. The concept is highly attractive as it enables wireless neural stimulation without limitation on penetration depth or the requirement of invasive surgeries.

Microstimulation has been an invaluable tool for neuroscience researchers to infer functional connections between brain structures or causal links between structure and behavior. In recent years, therapeutic microstimulation is gaining interest for the restoration of visual, auditory and somatosensory functions as well as emerging applications in bioelectronic medicine. Current neural stimulation parameters and safety limits need to be revised for microelectrodes using more systematic and advanced methodologies.

Our long-term goals are to better understand the response of neurons to artificial stimulation, and, to use this knowledge to develop new and more effective strategies for stimulating non- or improperly-functioning neurons of the CNS. The development of models that comprehensively and accurately predict the response of neural populations to electric stimulation has proven challenging, in part because of the significant morphological differences that can exist even between nearby cells, and, a lack of understanding as to how such differences shape each cell’s response to stimulation.

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.