Cooperative Agreements

ABSTRACT A major challenge in neuroscience is to uncover how defined neural circuits in the brain encode, store, modify, and retrieve information. Adding to this challenge is the fact that neural function does not operate in isolation but rather within living, behaving animals. Great technological advances over the past decades have allowed researchers to begin to optically measure and modulate neural activity but these approaches are often limited to head-fix animals when studying neural function at spatial and temporal scales relevant to internal neural circuit dynamics.

PROJECT SUMMARY/ABSTRACT Our proposed efforts align directly with a goal of RFA-NS-18-019: optimization of transformative technologies for modulation in the nervous system. Specifically, we seek to optimize microelectrode arrays (MEAs) and ultra-microelectrode arrays (UMEAs) for large-scale circuit manipulation that will control neural activity at cellular resolution with high temporal resolution.

PROJECT SUMMARY A central goal of neuroscience is to understand animal behavior in the context of the information processing properties of neuron ensembles. Neurons are circuit nodes in the brain information processing network, but they are also cells that express hundreds of genes that may make important contributions to determining their activity patterns. The relationship between gene expression, neuron projections, neuron activity, and behavior have been, individually, major avenues for investigation in both molecular and systems neuroscience.

Abstract Among the BRAIN Initiative’s most important achievements are the genetic identification of many new neurons- types and the creation of genetic tools to access these cell types.

Project Summary / Abstract A number of recent observations suggest that complex brain functions in the mammalian brain emerge from highly parallel computation in which information about sensory inputs, internal states, and behavioral parameters are mapped onto highly distributed brain-wide neuronal populations. This calls for neurotechnologies that allow for large-scale recording of neuro-activity across tissue depths and brain regions at physiological timescales and cellular resolution in awake and behaving animals.

Understanding human brain function requires knowledge of its connectivity: how one structure causally influences other components of the network. A wide range of neurological and psychiatric disorders prominently involve dysfunction of connectivity, including neurodegenerative diseases, autism, and mood disorders. Yet current methods provide only indirect measures of connectivity, and none can directly test how one brain structure causally influences another at the level of the whole brain.

Project Summary The rapid formation of new memories and the recall of old memories to inform decisions is essential for human cognition, but the underlying neural mechanisms remain poorly understood. The long-term goal of this research is a circuit-level understanding of human memory to enable the development of new treatments for the devastating effects of memory disorders. Our experiments utilize the rare opportunity to record in-vivo from human single neurons simultaneously in multiple brain areas in patients undergoing treatment for drug resistant epilepsy.

Project Summary/Abstract Deep Brain Stimulation (DBS) is a surgical procedure that is used to treat the debilitating symptoms of Parkinson's Disease (PD). In the process of surgically implanting the stimulating electrodes, surgeons and researchers have a unique opportunity to measure and manipulate the activity of individual neurons while the awake PD patient performs a perceptual, cognitive, or other kind of relatively simple task.

Project Summary/Abstract Decades of research and clinical observations have established that episodic memory, the ability to remember recently experienced events, depends on the hippocampus and associated structures in the medial temporal lobe (MTL), including entorhinal, perirhinal and parahippocampal cortices [1, 2]. It is thought that the neuronal mechanisms supporting episodic memory for spatial context involves place and grid cells found in the MTL that increase in firing rate when an animal is in a specific location during navigation [3-7].

A Brain Circuit Program for Understanding the Sensorimotor Basis of Behavior Abstract The Project team's long-term goal is to develop a comprehensive theory of animal behavior that explicitly incorporates neural processes operating across hierarchical levels — from circuits that regulate the action of individual muscles to those that regulate behavioral sequences and decisions. Our innovative approach is guided by the notion that different brain regions are not linked within a single neuroanatomical tier, but rather constitute a series of hierarchically nested feedback loops.