Understanding Circuits

Abstract The transformation of visual cues into appropriate behavior requires the collaboration of diverse neurons across distant brain areas. A fundamental gap in our knowledge about these visuomotor transformations is understanding how these neurons are functionally connected, shaping neural response dynamics that give rise to behavioral output. This gap is due to the inaccessibility of mammalian model systems, in which simultaneous in vivo observation and manipulations across the brain is impossible as well as a lack of real-time computational frameworks that can capture these dynamics.

Feedback and feedforward gating of sensory signaling through timing in the thalamocortical loop Nearly all sensory experience begins in the periphery, generating sensory signals travelling through the thalamus before reaching neocortex. Despite numerous anatomical and functional investigations into the feedforward projections from thalamus to primary sensory cortex (TC), significantly less is known about the extensive reciprocal corticothalamic (CT) feedback pathway that provides ~40% of input to the thalamus.

Project Summary Neuroscience is entering a new era, where large-scale neural network models can be tested with unprecedent- edly rich measurements of neural activity. This proposal develops a general methodology for linking theory to experiment in this new era and applies the methodology to the problem of primate face recognition.

Project Summary The cerebellum is essential for coordinating motor behavior through rapid adjustments of ongoing movements. To refine movement, the cerebellum processes motor and sensory information, and transmits output that ultimately modulates motor neuron activity to ensure successful execution. The path through which the cerebellum can influence limb movement is through output circuits in the cerebellar nuclei (CN). Yet little is known about how CN circuits are organized and whether discrete pathways are dedicated to specific motor functions for limb control.

Project Summary Animals interact with the world through dynamic, iterative sensory-motor processes that guide their ongoing movement. Odor-guided navigation is the basis for fundamental natural behaviors such as finding food sources, but little is known about the nature of the sensory signals that inform adaptive changes in locomotion. Here we propose to test how spatial information is encoded by distributed activity in the olfactory bulb, and how this information is decoded by higher-order brain areas.

PROJECT SUMMARY/ABSTRACT Higher brain functions include the ability to learn expectations about the world, update those expectations appropriately when given new sensory information, and use those continually updating expectations to guide behavior. How neural circuits implement these flexible information-processing dynamics is not known.

Project Summary (Overall: Cracking the Olfactory Code) Sensation drives perception, which informs decisions and actions. Olfaction is the main sense used by most animals to interact with the environment. However, olfaction remains shrouded in mystery — we do not know which molecular odorant features matter to the olfactory system and which do not, how information about these features is recombined to create holistic odor representations within the brain, or how those representations relate to perception.

Project Summary: Overall Local networks within the spinal cord represent an essential computational layer for the control of limb-driven motor behaviors, integrating descending and sensory inputs to coordinate dexterous motor output. Significant advances have been made in characterizing the developmental programs that specify the core cardinal interneuron types that make up these motor networks. This knowledge has been used to develop a battery of mouse genetic reagents for spinal circuit anatomical and functional dissection.

Project abstract Animals, including humans, interact with their environment via self-generated and continuous actions that enable them to explore and subsequently experience the positive and negative consequences of their actions. As a result of their interactions with the environment, animals alter their future behavior, typically in a manner that maximizes positive and minimizes negative outcomes.

Project Summary: The decision to commence a new behavior often requires termination of the ongoing behavior. This implies that the many drive states produced by an animal impact not only the neural circuits underlying their directly associated behaviors, but also those of many other behaviors. My lab has shown that the mating behaviors of male Drosophila are under motivational control and may be abandoned in the presence of stimuli evoking competing drives—depending on the relative intensities of the contending drives.