Circuit Diagrams

Cortical Signature and Modulation of Pain Abstract/Project Summary Pain perception contains two main dimensions: the sensory-discriminative and the affective-cognitive aspects. In this proposal, we will focus on the cortical signature and modulations of the sensory aspects of pain using mouse models. Pain can be largely divided into inflammatory or neuropathic pain. A common condition in both types of pain is mechanical allodynia: externally applied innocuous gentle touch becomes painful.

Project Summary Two of the most fundamental questions of sensory neuroscience are: 1) how is stimulus information represented by the activity of populations of neurons at different levels of information processing? and 2) what features of this activity are read at the next levels of neural processing to guide behavior? The first question has been the subject of a large body of work across different sensory stimuli. To answer the second question, one needs to establish a causal link between neuronal activity and behavior.

PROJECT SUMMARY Sensory perception involves processing incoming sensory input and interpreting that information through rules generated from prior experience. Stimulus features need to be bound together to form more complex sensory representations and then associated with a valence or action outcome to give meaning to those representations. In the mammalian neocortex, the formation of sensory representations is believed to occur through processing that is distributed across several cortical areas.

Sensory processing is a way to understand neural circuits and their functions during behavior. Behavioral context strongly affects sensory processing. For example, a brief visual stimulus is easier to detect if it appears in a predictable spatial location. Attention to visual space strongly enhances neural and behavioral responses to stimuli in those locations, but the detailed neural mechanisms producing these effects remain unknown.

PROJECT SUMMARY We seek to better understand how the brain processes olfactory information by focusing on how circuits of the olfactory bulb control two fundamental aspects of sensory processing: the relationship between sensory input and olfactory bulb output as a function of stimulus intensity, and tuning of response specificity by lateral inhibition.

Abstract Motion detection, a fundamental computation of the visual system, begins in the retina. In the mammalian retina, the direction of moving objects is computed by the direction-selective circuit. The retinal output of this circuit is provided by direction-selective ganglion cells (DSGCs). These cells are strongly activated by motion in their preferred direction, but are suppressed by motion in the opposite, or “null”, direction.

Functional interactions between the entorhinal cortex and hippocampus are critical for spatial navigation and episodic memories related to people, places, objects and events. Canonically, medial entorhinal cortex (MEC) processes spatial information while lateral entorhinal cortex (LEC) processes non-spatial contextual information.

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”.