Circuit Diagrams

Project Abstract Current common methods for measuring somatosensory function in preclinical rodent models generally rely on withdrawal responses to uncomfortable or painful stimuli. These tests can be stressful to the animal, while also yielding a high variability in measured responses, and repetitive testing in longitudinal models may even result in chronic pain states. To better understand the connection between physiology and perception of touch and proprioception, researchers need a modern, off-the-shelf assessment system to administer and quantify trained, volitional behaviors.

Project Summary Intracortical microstimulation (ICMS) of the sensory cortices is an emerging approach to restore sensation to people who have lost it due to neurological injury or disease. ICMS of somatosensory cortex has been used in clinical trials to restore sensation to the hands of people with spinal cord injury and, more recently, was used to restore vision to a person with blindness. The sensations evoked by ICMS are dependent on the stimulated electrode and selected parameters.

Over the past 15 years, new microscope technologies and methods for high throughput imaging have revolutionized structural biology by extending the resolution and scale of datasets in 3 dimensions. The resulting image volumes are more typically hundreds of GB to even tens of TB and for large volume electron microscope images of brain, can approach PB sizes. These file sizes pose challenges for image analysis, and communication of a representative set of raw data and quantification.

Abstract Microelectrode arrays (MEAs) have great potential for therapeutic use in direct brain-computer interface (BCI) control of robotic prostheses to improve the lives of patients suffering from debilitating conditions related to loss of limbs or limb function. MEAs also have the potential to restore loss of sensory perception in vision, hearing, and tactile sensation by applying patterned current stimulation to sensory neurons.

Project Summary Learning and performing complex skills such as speech or music requires precise control of motor variability. While elevated motor variability can spur the learning of new behaviors, excessive variability can impair performance of learned skills. How the brain controls motor variability during learning and in expert performance remains unclear. Intriguingly, the basal ganglia (BG) is an important source of motor variability in both health and disease, and is a key site where dopamine (DA) reinforces more successful behaviors.

Decision making is a fundamental cognitive process, and many decisions are based on gradually accumulated evidence. Thus, it is critical to understand the mechanistic basis underlying this accumulation process. Traditional models of evidence accumulation are based on low-dimensional attractors where individual neurons show ramping activity throughout a trial. However, an increasing number of studies have observed choice-selective sequences in their neural recordings, in which neurons fire transiently and sequentially with the subset of neurons that fires indicative of the animal’s choice.

PROJECT SUMMARY Animals can exhibit goal-directed behaviors in novel environments, despite limited experience with them. How does the brain make and use inferences about the underlying statistics and generative structure of environments to guide behavior? The field of reinforcement learning refers to this capacity as “model-based” reasoning, meaning that it relies on an internal model of the structure of the world. Critically, this internal model can be used to flexibly estimate the best actions by mental simulation or planning, without direct experience.

TITLE: IDENTIFYING THE NEURAL MECHANISMS OF GOAL-DIRECTED DECISION-MAKING IN PARKINSON’S DISEASE USING CLOSED-LOOP DEEP BRAIN STIMULATION PROJECT SUMMARY People with Parkinson’s disease commonly suffer from non-motor symptoms, including motivation deficits, that impact quality of life more than classical

Electrophysiology is a critical technology in neuroscience as a direct measure of neuronal functions. It has become routine for scientists to record and stimulate neuron populations in different brain regions in awake behaving animals, correlating activity with behavior. However, it has been insurmountable for the same electrophysiology to perform well in the spinal cord of behaving animals.

PROJECT SUMMARY / ABSTRACT Neuropeptide modulation of neuronal circuits is strongly linked to many crucial behaviors such as exploration, stress, memory formation, learning, and many pathophysiological conditions. Unfortunately, neuropeptides are notoriously difficult to understand because many methods are not well-positioned to isolate neuropeptide function accurately in space and time within the brain. Genetically-encoded fluorescent protein sensors could provide precise monitoring with high-spatial and temporal resolution and cell-type specificity.