Circuit Diagrams

ABSTRACT: The lateral habenula (LHb) impacts motivated behavior through dense direct and indirect projections to midbrain dopaminergic and serotonergic neurons. Some LHb neurons project directly to midbrain dopaminergic or serotonergic neurons; others project indirectly through one of multiple types of midbrain GABAergic neurons. Similar to dopaminergic neurons, the LHb encodes reward prediction error (RPE) - the discrepancy between expected and actual value – a powerful computation that guides learning from environmental feedback.

PROJECT SUMMARY When Confucius said, “Tell me who are your friends, and I’ll tell you who you are,” he was noticing that how we behave and communicate is shaped by who we choose to hang out with every day. We constantly mimic the mannerisms and behaviors of friends and loved ones. Yet the neural basis of how we imitate, and more importantly who we choose to emulate and why, is largely unknown. Parrots provide a powerful yet untapped model system for social learning.

Project summary Although single neurons occasionally project to a single downstream target, it is more often the case that their axons collateralize and project to multiple distinct anatomical areas. This feature of neuroanatomy has been appreciated for over 100 years and is theorized to be critical to coordinating brain-wide states. Despite this, collateral projections have largely been overlooked in contemporary neuroscience.

Summary Genetic technologies have revolutionized the way scientists can dissect out brain circuitry by inserting G protein-coupled receptors that enable selective modulation of neurons in target structures. Amongst them, a promising tool,DREADDS (designer receptors exclusively activated by designer drugs) is used to modulate neural activity pharmacologically in targeted brain regions. Unfortunately, DREADDS also require invasive methods to deliver the genes that express the receptor.

Summary Strategic behaviors often take account of uncertainty. For example, if we are presented with two conflicting pieces of information, we give less weight to the more uncertain source of information – i.e., the source of information that leads to lower accuracy overall. Notably, even insects behave as if they make strategic use of their own uncertainty. Importantly, the neural correlates of uncertainty are essentially unknown. In this collaborative project, we will use modeling and neural imaging to identify the neural correlates of uncertainty.

Project Summary / Abstract Systems neuroscience has viewed the brainstem noradrenergic nucleus, Locus Coeruleus (LC), as the source of a global arousal signal, which modulates cognitive functions by altering operations throughout the entire central nervous system. This is achieved, presumably, by this small collection of only ~1,600 neurons in rodents spiking synchronously.

ABSTRACT A critical step towards understanding how neural circuits drive behavior is the ability to record the activity of all neurons in an organism while it interacts with its environment in an unconstrained manner. A promising vertebrate model system in this regard is the zebrafish larva, which performs complex visually-driven behaviors such as hunting from an early age, and due to its transparency allows large-scale neural imaging at single- neuron resolution.

Project Summary Blindness in the United States is a large and increasing problem. Any significant vision loss is debilitating, but profound blindness is devastating to an individual’s ability to be independent and to perform everyday tasks and activities. Hundreds of thousands of people in the United States suffer from profound blindness, and most of these currently have no hope of vision recovery. Recently, a retinal prosthesis has become available in Europe, U.S., and Canada for people with profound vision loss from Retinitis Pigmentosa, a degenerative retinal disease.

PROJECT SUMMARY / ABSTRACT Recent advances in design and actuation have led to important improvements in prosthetic limbs. However, these devices lack a means for providing direct sensory feedback, requiring users to infer information about limb state from pressure on the residual limb. Lack of sensation limits their ability to control the prosthesis and leads to slow gait and increased risk of falling. There is also evidence that lack of sensory feedback contributes to phantom limb pain (PLP), and that electrical stimulation at the dorsal root ganglia (DRG) can reduce PLP.

Abstract DBS therapy for Parkinson's disease is now the primary surgical approach for Parkinson's disease, recently FDA approved at 4 years after onset of disease. However, this therapy is still limited to treatment of a subset of motor symptoms (ie, tremor, rigidity, bradykinesia and dyskinesias) and requires considerable postoperative clinical adjustment to program and maintain function. A number of improvements to DBS for PD are being tested, including changes in patterns of stimulation and specific targets.