Understanding Circuits

Summary Enormous progress has been made about the neural substrates of Pavlovian fear conditioning. In this paradigm, the association between an initially neutral sensory stimulus with an aversive event (footshock) leads to the transformation of the neutral stimulus into a conditioned stimulus (CS) that elicits fear responses in the form of immobility, potentiated startle, changes in heart rate, etc, which were not evoked by the neutral sensory stimulus.

ABSTRACT We will use our expertise in somatosensory organization and plasticity to develop novel and automated solutions for cell identification based upon neural activity, in order to decode the algorithms neural circuits use for information processing. Extracellular recordings in sensory cortex have been thought to primarily represent excitatory neuron activity, since these cells comprise ~80% of the total cell population.

Project Summary/Abstract The goal of this exploratory research project is to improve understanding about the mechanisms by which mammalian neural circuits decode environmental chemosensory information and use that information to support survival and reproduction. Specifically, the proposed research will investigate cell type-specific neural codes in the parallel brain pathways of the mouse accessory olfactory system (AOS).

Summary Multimodal sensory information is converged through poly-synaptic pathways to the hippocampus to form integrated representations and encode memories of the world, which in turn guide our future behavior through multiple poly-synaptic downstream pathways. It is well known that each of the brain regions in this circuit consists of various neuronal cell types or groups which are distinct in connectivity and functions.

Abstract The prefrontal cortex is thought to play a crucial role in cognitive flexibility, in part by updating a person's expectations about the external world and the likely consequences of candidate actions based on the feedback gained from past actions. Deficits in this form of cognition occur in multiple psychiatric conditions in which prefrontal cortex is implicated. Despite much research, the mechanisms by which prefrontal neural circuits contribute to flexible decision-making and switches in cognitive strategy remain unclear.

SUMMARY Norepinephrine is a neurotransmitter thought to be involved in driving behavioral flexibility. It is released by a small number of neurons throughout the neocortex. Little is known, however, about what signals these neurons provide, and how targets in neocortex use those signals, in the context of well-controlled behaviors in mammals. This proposal aims to determine functions of norepinephrine-releasing neurons in the locus coeruleus, the primary source of forebrain norepinephrine.

Abstract    A major challenge in the treatment of neurological diseases is the elaborate and diffuse nature of neural  circuits, where physically proximal neurons are engaged in functionally different pathways. The ability to target  neurons based on function, rather than location, is critical to improving treatments for disease. In Parkinson’s 

PROJECT SUMMARY Moment-to-moment fluctuations in behavioral and brain states have been shown to have profound effects on perception and behavior in both humans and experimental animals. The variability in behavioral responses caused by these fluctuations have real world effects because they can cause an individual to respond inappropriately in high stakes and demanding situations, such as driving a car or operating on a patient.

Many animal behaviors are organized into long-lasting states, perhaps most strikingly in the sleep/wake and emotional states that mammals display. However, the fundamental mechanisms that allow animals to initiate, maintain and terminate these states are unknown. Biogenic amine and neuropeptide neuromodulators are critical for the generation of behavioral states, but a mechanistic understanding of how neuromodulators act on circuits to generate stable circuit-wide patterns of neural activity has been lacking, largely due to the complexity of neuromodulation in mammalian circuits.

Project Summary / Abstract Encoding of environmental location and navigational behavior in mammals involves large ensembles of specific neuron types across multiple interacting brain regions. “Place cell” and “grid cell” mapping of spatial location in the CA1 region of hippocampus and medial entorhinal cortex (EC), respectively, is thought to be fed forward to associative cortical brain regions including the posterior parietal cortex (PPC) and retrosplenial cortex (RSP) to map conjunctions of egocentric and external spatial relationships.