Research Projects

Thalamocortical state control of tactile sensing: Mechanisms, Models, and Behavior Despite the fact that the sensory thalamus plays a major role in shaping sensory representations in cortex, and thus shaping our percepts, most of what we know has been determined through electrophysiological investigation of the thalamus in-vitro or in the anesthetized brain. Properties of thalamic activity such as mean firing rates, timing and synchrony, and tonic/burst firing directly determine how sensory inputs are represented in the spatiotemporal activation of cortex.

Project Summary / Abstract Our brain provides us with a sense of where we are in space.

ABSTRACT Top-down feedback connections between “higher” and “lower” brain areas are quite common, but their functional role remains a mystery. This general principle applies to the olfactory system, in which the olfactory bulb receives dense feedback innervation from its cortical targets. Here, we propose techniques with which feedback neurons can be targeted by a viral/transgenic intersectional strategy in mice. Using this strategy, we will identify feedback neurons during electrophysiological recordings by optogenetic tagging.

PROJECT SUMMARY The amygdala plays a central role in diverse learned behaviors. By integrating the sensory information with stress, punishment, and reward signals, the circuitry within the amygdala is thought to be modified during learning to mediate specific behavioral outcomes. However, the circuit principles governing what is changed and how different types of learning give rise to qualitatively distinct behaviors remains largely unknown.

Project Summary / Abstract A fundamental but unsolved question in neuroscience is how specific connections between brain cells (neurons) underlie information processing. Circuits in the cerebral cortex—the part of the mammalian brain that underlies high-level sensory, motor, and cognitive function—consists of tens of thousands of neurons, each of which sends and receives thousands of connections. Perhaps the biggest reason we don't understand the cerebral cortex is that we don't have an actual wiring diagram of any single cortical circuit.

ABSTRACT Resting state networks are a fascinating yet poorly understood phenomenon. Sets of spatially separated regions show correlated slow fluctuations in fMRI BOLD signals, most obvious when subjects are at rest. These networks appear to have clinical imporantance: brain injuries perturb resting state networks, and multiple clinical disorders, including depression, dyslexia and prosopagnosia, are associated with specific resting state network abnormalities.

Attention deficit symptoms are frequently observed in psychiatric disorders, yet finite understanding of the neural circuits mediating attentional behavior has limited pathophysiologic insight. Previous studies in humans and rodent demonstrate that the frontal cortex—especially the anterior cingulate cortex (ACC)— plays a key role in implementing a top-down control of attention. However, the precise neural circuit mechanisms mediating attention remain largely unknown.

Project Summary Understanding the circuit mechanisms that give rise to perception and behavior requires linking neuronal activity to connectivity. This can be accomplished at multiple scales and ideally can be related to further studies using activity manipulations to demonstrate causality. Recent work in the mouse visual system has revealed the contributions of specific cell types to the generation of visual receptive field properties as well as state-dependent changes in the representation of visual information.

Histone modification carries rich epigenetic information that constitutes a mechanism of cellular memory. Single cell analysis of histone modification in conjunction with transcriptome could help uncover this critical layer of cellular memory and lead to better definition of cell types and states in the brain. Here, we propose to develop an ultra-high throughput method, known as Paired-Tag, for joint profiling of histone modifications and transcriptome in single cells.

Project Summary The BICCN has recently completed a broad survey of the cellular components of motor cortex, including transcriptomic profiling, patch-seq, multiplexed FISH, inter-areal connectivity, and single neuron morphology. Missing from this view is a detailed picture of how individual neurons and neuronal types interconnect, in large part because acquiring a comprehensive picture of individual neuronal connections is best achieved with the difficult methods of large-scale electron microscopic reconstructions.