Research Projects

Project Summary A forebrain structure, lamina terminalis (LT), plays a key role in both sensing internal water balance and regulating thirst through its downstream neural circuits. Recent studies have identified genetically-defined neural populations and circuit organization that control the initiation of drinking. The activity of these thirst neurons are rapidly suppressed with the onset of water consumption prior to absorption of ingested water. These results suggest that the LT integrates the homeostatic need and real-time satiety signals to optimize drinking.

Project Summary: Natural sensory inputs are typically complex, and often combine multiple modalities. Human speech, for example, combines auditory signals with visual cues, such as facial expressions, that inform the interpretation of the spoken words. As individual sensory pathways only provide a partial representation of the sensory information available, selecting the context-appropriate behavioral response to a multimodal stimulus often requires integrating information across modalities.

ABSTRACT A distinguishing feature of the brain is that its circuitry isn’t computationally static, it adapts to experience. Understanding the circuit mechanisms for adaptive behavior carries two-fold potential benefits - revealing the brain’s learning rules and identifying key behaviorally significant functional “nodes”.

Summary GABAergic interneurons (INs) are a diverse group of neurons with critical roles in signal processing in the cerebral cortex. Moreover, malfunction of these neurons has been implicated in a number of diseases ranging from epilepsy to schizophrenia, anxiety disorders and autism. This project is focused on the GABAergic INs that express the neuropeptide somatostatin (SST). These cells represent the second largest family of INs in the neocortex.

Dendritic spines cover dendrites of most mammalian neurons and receive almost all excitatory connections in the cortex. Although their role in these circuits is therefore likely to be crucial, the function of spines is still poorly understood. Spines are chemical compartments, and this could provide the biochemical isolation necessary to implement input-specific synaptic plasticity. But recent experiments have suggested that, in addition, spines could compartmentalize voltage.

SUMMARY/ABSTRACT Anthropoid primates (monkeys, apes, and humans) are distinguished from their phylogenetically nearest relatives (lemurs, tree shrews, and rodents) by an elaboration of the cerebral cortex including changes in cellular composition of the cortical circuit. However, we know very little about the function of different cell types in the anthropoid primate cortex partly because of slow adoption of the tools that have been so successful in rodents (cell type-specific optogenetics and imaging).

Abstract One of the major barriers to understanding how neural circuits give rise to behavior is that typical experimental preparations make it difficult to study these circuits across different brain areas. Recent advances in microscopy and calcium sensors have made it possible to simultaneously record up to thousands of individual neurons, and optical methods have made it possible to stimulate hundreds at a time, but current approaches, which stimulate only subsets of predetermined neurons, are not adequate for dissecting large-scale neural circuits.

Project Summary Aggression is a fundamental social behavior. Though widespread, the stimuli that modulate aggression differ between species. Primates rely strongly on visual cues, while in rodents and insects olfactory stimuli are essential. Since mice and flies are the leading models of modern aggression studies, the mechanisms by which visual neural circuits modulate aggression remain largely unknown.

Our senses aren’t passive. Rather, we actively seek relevant information via sampling movements. However, experiments in sensory systems often restrict sampling movements to simplify stimulus delivery and allow large scale imaging and electrophysiology. But whether sensory systems function equivalently in restraint vs free sampling remains an open question. The mouse olfactory system presents a perfect opportunity to address these issues. Mice are in constant motion, actively sniffing throughout their environment.

SUMMARY The brain transforms raw sensory input into perception and cognition, and this transformation relies on computations performed across neuronal circuits. Fortunately, the anatomy of cortical microcircuits in non- human primate models is much better understood today than decades ago. Indeed, sensory information travels in the cerebral cortex along feedforward and feedback pathways. While bottom-up feedforward connections have been extensively examined over the past several decades, the functional role of feedback projections continues to remain mysterious.