Training

Project Summary/Abstract The brain undergoes extensive synaptic plasticity and circuit refinement during development. Similar changes recur throughout life during learning in a more narrowly constrained manner. Understanding how neuronal connections and activity are adaptively remodeled to accommodate a changing world remains an outstanding question in neuroscience research. Recent technological innovations provide unprecedented access to address this.

Project Summary/Abstract Circuits in the brain control motor output to generate the precise behaviors required for survival. Dysfunction of these circuits results in devastating movement disorders such as Parkinson’s disease and amyotrophic lateral sclerosis. It is important to understand how the brain normally controls behavior by understanding what features of motor output are encoded in individual neurons and how these representations are organized across a neuronal population. This K99/R00 proposal will support Dr.

Project summary Nausea is an unpleasant sensation of visceral malaise often accompanied by an involuntary urge to vomit. Nausea responses to toxin ingestion and infection are evolutionarily beneficial survival behaviors that avoid or expel toxins which may cause peripheral tissue damage. However, the sensation of nausea can also be maladaptive, as many treatments for cancer, diabetes, and other illnesses induce nausea as a major side effect, while current anti-emetic drugs have only limited efficacy.

Project summary Our lives unfold over time, weaving rich, dynamic, and multisensory information into a continuous experience. However, we remember this as a series of discrete events. For example, the memory of a two-hour movie consists of a few memorable moments tied to the main story. During encoding, we segment deviant events and associate relevant events. During retrieval, we utilize the temporal association among encoded events to search for specific memory information.

Project Summary This proposal seeks to investigate sex hormone effects on reward and aversion-related behaviors through mapping of Lateral Habenula (LHb) circuits. The LHb is a central hub important for encoding aversive information and coordinating motivated behaviors, actions critical for survival. Dysfunction in LHb-dependent circuits contribute to a diverse set of disordered behaviors, such as aberrant processing of positive and negative valence, anhedonia, depressive symptomology, and maladaptive stress response, to name a few.

PROJECT SUMMARY To flexibly execute behavior, choices are made based on previous outcomes that will maximize reward. Crucially, learning the value of each action to obtain a reward is thought to drive this decision making process. In a value-based decision making framework, these values are first computed and then used to select and execute actions. Dysfunction in this decision making process is evident in many neuropsychiatric disorders including addiction and in patients with frontal cortical damage who show an inability to flexibly adjust or adapt their behavior.

The brain uses the combined physiology of many cells to transform incoming sensory signals into internal representations. This process is critical for the animal’s survival because it underlies the animal’s ability to identify environmental cues and associate them with the condition of their situation. While sensory representation at the somatic level is well-studied, exploration of this phenomenon at the synaptic level is lacking.

Project Summary/Abstract Learning how spontaneous neuronal activity shapes embryonic brain development is critical for understanding neurodevelopmental processes, with implications in neurological or neuropsychiatric disorders. Early sporadic activity is essential for the formation of mature correlated neuronal networks. To date, we have had success in identifying the motor circuit as the first circuit to function in a developing zebrafish embryo. In addition, a few neurons, the “leader cells”, are the first neurons to obtain spontaneous neuronal activity.

PROJECT SUMMARY Serotonin has been long been recognized as an important modulator of mood and behavior, yet it projection- specific dynamics are little understood. While serotonin has been well studied in anxiolytic contexts, activity of certain serotonin projections works to increase stress behaviors. In particular, serotonergic projections from dorsal raphe to the anterodorsal bed nucleus of the stria terminalis have been shown to be anxiogenic.

PROJECT SUMMARY A core feature of a number of psychiatric illnesses is the disordered estimation of the predictive relationship between a given cue and an outcome. This failure to appraise and generate appropriate behavioral responses is true for cues that both are rewarding and aversive. For example, in post-traumatic stress disorders innocuous stimuli can elicit intense aversive motivational responses even though these were encountered in a safe and familiar context.