Circuit Diagrams

ABSTRACT The public health burden of Treatment Resistant Depression (TRD) has prompted clinical trials of deep brain stimulation (DBS) that have, unfortunately, produced inconsistent outcomes. Potential gaps and opportunities include a need: (1) to better understand the neurocircuitry of the disease; (2) for precision DBS devices that can target brain networks in a clinically and physiologically validated manner; and (3) for greater insight into stimulation dose-response relationships.

PROJECT SUMMARY Deep brain stimulation (DBS) of the subcallosal cingulate (SCC) white matter is an emerging new treatment strategy for treatment resistant depression (TRD) with published studies demonstrating sustained long-term antidepressant effects in 40-60% of implanted patients.

Although neuroscience has provided a great deal of information about how neurons work, the fundamental question of how neurons function together in a network to produce cognition has been difficult to address. Our group has been at the forefront of developing methods that allow large scale monitoring of identified neurons, monitoring of voltage signals by optical means and elucidation of subcellular events in dendrites, all of which can now be done in awake behaving animals.

Project Summary Working memory, the ability to temporarily hold multiple pieces of information in mind for manipulation, is central to virtually all cognitive abilities. Recent technical advances have opened an unprecedented opportunity to comprehensively dissect the neural circuit mechanisms of this ability across multiple brain areas. The task to be studied is a common form of decision-making that is based on the gradual accumulation of sensory evidence and thus relies on working memory.

Understanding the mechanisms that the nervous system uses to control movement is critical for understanding brain and behavior, and one of the fundamental questions in neuroscience. The control of movement emerges from the activity of different motor control centers, that converge onto output systems, mostly located in the spinal cord. While the spinal circuits that underlie different aspects of motor control have been relatively well characterized, the way by which these circuits are coordinated by supraspinal motor control centers remains elusive.

Project Summary - A realistic multiscale circuit model of the larval zebrafish brain The working group of the BRAIN initiative (BRAIN 2025, a Scientific Vision) identified “the analysis of circuits of interacting neurons as being particularly rich in opportunity, with potential for revolutionary advances

PROJECT SUMMARY The monoamines, which include dopamine, norepinephrine, and serotonin, are evolutionarily conserved neurotransmitters that modulate the activity of excitatory and inhibitory neurons throughout the entire brain, and are thus essential for diverse aspects of physiology and behavior. Abnormalities of monoamine systems contribute to numerous brain disorders including schizophrenia, depression, and Parkinson's disease.

Project summary: Consolidating transient sensory experiences into long-lasting memories is a fundamental function of the brain, linked to synaptic plasticity. The importance of sleep for promoting this process, and the disruptive effect of sleep deprivation on it, have been appreciated for nearly a century.

Abstract Sleep is essential for the maintenance of our cognition and neurological functions, and both quality and quantity of sleep are critical. We likely have known this for the entire human history. Yet, we remain astonishingly ignorant on how the quality and quantity of sleep are regulated. Excitingly, nature has provided us a very small number of human subjects who are genetically wired to sleep shorter hours per day (thus more efficiently). These people usually live a long and healthy (both physically and mentally) life.

Summary Enormous progress has been made about the neural substrates of Pavlovian fear conditioning. In this paradigm, the association between an initially neutral sensory stimulus with an aversive event (footshock) leads to the transformation of the neutral stimulus into a conditioned stimulus (CS) that elicits fear responses in the form of immobility, potentiated startle, changes in heart rate, etc, which were not evoked by the neutral sensory stimulus.