Circuit Diagrams

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.

Project Summary The function of the nervous system is dependent on complex interactions between networks of neurons composed of multiple neuron types. Understanding how these networks function both in health and disease is dependent on understanding the precise connectivity between specific neuron types and their functional interactions in the intact brain.

PROJECT ABSTRACT Recent advances in microscopy permit volume imaging - the near-simultaneous imaging of many neurons in a circuit - with 2-photon (2P) excitation, yielding new insights into the circuits underlying relatively simple behaviors. Volume imaging techniques and 2P excitation have been limited mainly to small animals such as rodents, including studies of mouse cortex.

Project Summary Opioids as a pain medication has been the most preferred pain treatments in order to provide quick relief from severe pain. Decades of opioid abuse have triggered negative impact on pain therapies. Understanding of neural circuits that are actually driving pain is essential in order to develop more effective and safer pain therapies. Neuroanatomical studies have allowed us to define the regions and subsets of neurons that are important for pain.