Understanding Circuits

Project Summary/Abstract The overall goal of this project is to determine how output from the basal ganglia influences cerebral cortical activity in the processes of decision making, motor planning, and movement execution. The studies will employ mice as the best suited species in order to bring modern optogenetic and genetically encoded sensor technologies to bear on this critical gap in our understanding of brain function. In aim 1 we address the impact of basal ganglia output on network activity in cortex across sensory and motor areas.

Neural computation for innate behaviors in the superior colliculus The long-term goal of the proposed research is to understand how the brain makes sense of the onslaught of sensory data to extract just the few bits of relevant knowledge needed to make a decision. Specifically we will focus on innate behaviors of the laboratory mouse, such as the escape from a threat, the pursuit of small prey, and visual navigation.

Project Summary Behavior is movement, and the effective and efficient execution of movement has served as a fundamental evolutionary force shaping the form and function of the nervous system. Control of the forelimbs to interact with the world is one of the most essential achievements of the mammalian motor system, yet unfortunately these behaviors are particularly vulnerable to disease and injury. The execution of skilled limb movements requires the continuous refinement of motor output across dozens of muscles, suggesting the existence of feedback pathways that enable rapid adjustments.

SUMMARY To date, fundamental understanding of which features of odorants are decoded by the brain, and how information about these features is channeled through the olfactory system is still lacking. Odorants are sensed by the olfactory sensory neurons (OSNs) in the olfactory epithelium expressing specialized odorant receptors (ORs).

Abstract The cerebellum is critical for learning and executing coordinated, well-timed movements. The cerebellar cortex seems to have a particular role in learning to time movements. Since the 1960's and 70's, we have known the architecture of the cerebellar microcircuit, but most analyses of cerebellar function during behavior have focused on Purkinje cells.

Abstract To survive, living organisms must collect information about their environment and use it to select appropriate behaviors. However, information from the environment is often noisy, incomplete and ambiguous. Currently, no theory or model comprehensively explains how nervous systems solve the problem of navigation based on noisy information.

Project Summary/Abstract This project aims to investigate the circuit mechanisms enabling an ethologically relevant sensorimotor transformation. Specifically, we characterize the neural basis for rapid vocal exchanges in the singing mouse (Scotinomys teguina), a highly vocal neotropical rodent species capable of producing an audible, stereotyped song. Pairs of S. teguina often precisely coordinate the timing of their vocalizations in a process known as countersinging.

Working memory maintenance is fundamental for the orderly pursuit of goals in the face of irrelevant, distracting stimuli. Both prefrontal and visual areas are thought to contribute to the maintenance of items in working memory, but the exact nature of the interaction between these areas has yet to be causally examined. This proposal combines neurophysiological recordings of single unit activity and local field potentials with pharmacological manipulations of the prefrontal cortex, to determine its contribution to memory-driven changes in neural activity and synchrony within visual areas.

ABSTRACT Visual learning is critical to the lives of human and non-human primates. Visuomotor association, the assignment of an arbitrary symbol to a particular movement (like a red light to a braking movement), is a well- studied form of visual learning. This proposal tests the hypothesis that the brain accomplishes visuomotor associative learning using an anatomically defined closed-loop network, including the prefrontal cortex, the basal ganglia, and the cerebellum.

The mammalian cortex plays a critical role in integrating multiple streams of information to guide adaptive behavior. For example, head direction (HD) information is combined with visual and spatial input in the mouse retrosplenial cortex (RSC). Accurate integration of these signals is a necessary component of navigation: recognizing a distant landmark while facing north vs. facing south has very different interpretations for one's position and future actions.