Research Projects

Norepinephrine modulation of neocortex during flexible behavior

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.

DELINEATING CELL-SPECIFIC OUTPUT PATHWAYS OF THE GPe THAT SUPPORT LONG-LASTING BEHAVIORAL RECOVERY IN DOPAMINE DEPLETED MICE

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 

Behavioral state modulation of sensorimotor processing in cerebellar microcircuits

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.

Neuromodulatory control of collective circuit dynamics in C. elegans

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.

Subiculm circuits for cortical feedback regulation of spatial mapping and learning

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.

Development of predictive coding networks for spatial navigation

Development of predictive coding networks for spatial navigation Summary: Mammalian navigation uses internal models to predict the spatial-temporal statistical regularity of the sequence of environmental locations. Predictive coding theories view the brain as Bayesian interpreter that computes the difference between the external stimuli and an internal model of the world. It is increasingly understood that sequential spatial information is represented by temporal sequences of ensemble neuronal firing in the hippocampus.

Predictive models of brain dynamics during decision making and their validation using distributed optogenetic stimulation

Project Summary During behavior, the oculomotor system is tasked with selecting objects from an ever-changing visual field and guiding eye movements to these locations. The attentional priority given to sensory targets during selection can be strongly influenced by external stimulus properties (“bottom-up”) or internal goals based on previous experience (“top-down”).

the self-tuning brain: cellular and circuit mechanisms of behavioral resilience

ABSTRACT A major goal in clinical neuroscience is to develop efficient treatments to prevent or minimize the loss of brain function caused by pathological decreases or increases of neuronal activity, which are hallmarks of a wide variety of neurological disorders. Interestingly, in some instances, the brain has evolved mechanisms to partially correct abnormal neuronal function.

Circuit mechanisms underlying learned changes in persistent neural activity

ABSTRACT Persistent neural activity, a sustained response following brief stimuli that is observed in many brain networks, needs to be appropriately tuned to meet the exacting demands of various motor and cognitive tasks. One task that has been particularly amenable to understanding persistent neural activity is the oculomotor control of gaze position.

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