Understanding Circuits

In natural vision, recognizing objects based on the retinal image is challenging and is often an ill-posed problem because a single image is compatible with multiple interpretations. Nevertheless, the primate brain has a remarkable ability to understand ambiguous scenes and solve difficult object recognition problems. Converging evidence suggests that this process, especially in challenging contexts—e.g., occlusion or low-visibility environments—is based on the integration of sensory information with prior knowledge built from experience.

PROJECT SUMMARY/ABSTRACT An important longstanding goal in neuroscience research is to understand how large-scale spatiotemporal patterns of neural activity emerge in the brain and whether they have a direct role in shaping the brain’s computational processes and thereby mammalian behavior.

SUMMARY Norepinephrine (NE) is a neurotransmitter released by a small number of neurons in the locus coeruleus (LC), with extensive innervation of the neocortex. Prior work in humans and other mammals led to the hypothesis that LC-NE neurons modulate multiple forms of decision making. This proposal aims to test this overall hypothesis by studying LC-NE neurons in mice performing multiple decision-making tasks.

PROJECT SUMMARY Serotonin is an evolutionarily conserved neurotransmitter that modulates the activity of excitatory and inhibitory neurons throughout the entire mammalian brain and is thus essential for diverse aspects of physiology and behavior. Drugs that impact the serotonin system have been used to treat numerous brain disorders including depression, anxiety, and post-traumatic stress disorder. In the mammalian brain, serotonin neurons are clustered in the raphe nuclei of the brainstem, but project axons across the entire brain.

PROJECT SUMMARY/ABSTRACT Effective interpretation of sensory stimuli relies on the ability to discriminate stimulus features and link them to appropriate behavioral responses depending on past experience. Much remains unknown, however, about the roles that different neural pathways play in representing and learning these associations, and in particular, how information is distributed and combined among different pathways during learning and execution of behavior.

Abstract In many cognitive processes, information is processed in a parallel manner across many brain regions. This is thought to make our cognitive abilities highly tolerant to perturbations or neuron-loss because disrupted processes are compensated by other redundant neurons coding the same information. Yet, it remains poorly understood how interconnected networks of neurons are organized into redundant representations to produce robustness. We recently discovered that persistent activity in mouse frontal cortex during short-term memory is remarkably robust to perturbations.

PROJECT SUMMARY The courtship song of male zebra finches is a classical model for learning complex motor behaviors and shows important parallels to human speech and communication. Male zebra finches learn a song from an adult tutor and then reproduce this song throughout adulthood. The zebra finch model offers outstanding behavioral control that permits the investigation of general principles of the circuit basis of vocal learning and motor control.

Project Summary/Abstract This project will provide a more nuanced and mechanistic model of the role of sleep in memory consolidation, particularly as it pertains to procedural motor skill acquisition in a non-human primate model. Motor skill learning delineated by enhanced speed, automaticity, and accuracy of a correlate strongly with the duration of non-REM (NREM) sleep. Neural reactivations of daytime neural activity preferentially occur during NREM, and disruptions in NREM sleep negatively impacts memory consolidation.

Project Summary/Abstract In sensory decision-making, choices are influenced by non-sensory factors such as motivation, attention, and recent trial history. We seek to incorporate these influences into a drift diffusion model (DDM), by modeling non-sensory variables as deterministic modulators of the starting point or drift rate of sensory evidence accumulation. However, decision-making models are subject to confounds due to the non-stationarity and correlations in long-term behavioral data.

Years of study and theory about the unique role of the hippocampus in storing new memories has led to a general idea that the hippocampus generates a unique output code for every unique experience, that is projected back to the neocortex, where it becomes coupled to attributes of the experience that are widely dispersed over the cortex, thus enabling their coherent retrieval.