Circuit Diagrams

Project Summary: High frequency oscillations (HFOs) of intracranial EEG (iEEG) have the potential to identify the surgical resection area/seizure onset zone (SOZ) in patients with drug resistant epilepsy. However, multiple reports indicate that HFOs can be generated not only by epileptic cerebral tissue but also by non-epileptic sites often including eloquent regions such as motor, visual and language cortices.

Limited recovery of function after stroke remains a major problem for millions. Disability persists in many, especially when hand function is limited. Existing therapies are limited and many have difficulties with activities of daily living, even after rehabilitation. Electrical stimulation of the brain has been proposed and used in early studies to try and aid recovery. In animals, stimulation delivered to the brain at precise times may improve the effect of 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.

PROJECT SUMMARY Corticospinal axonal projections are critical for mammalian motor control. Their length and complexity makes them vulnerable to an exceptionally wide range of neurological disease processes including cerebrovascular disorders, demyelinating diseases, ALS, spinal cord injury, and more. Corticospinal research has naturally focused on cortical and spinal mechanisms. However, corticospinal axons, like those of other types of pyramidal tract neurons, can send branches to the midbrain, pons, and medulla along the way to the spinal cord.

PROJECT SUMMARY Rodent models are highly valuable for elucidating the molecular and cellular mechanisms of chronic pain. Because rodents cannot articulate their sensation, “pain-like” behaviors have been used as the proxy. However, sensitivity and specificity of many existing methods for measuring rodent “pain” sensation, especially “chronic pain”, are uncertain. Here we propose to explore the feasibility of a largely automated and data-driven behavioral assay for identifying spontaneous pain in freely behaving mice.