Systems Neuroscience

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.

Abstract This study aims to understand how the ensemble activity and network architecture of a neuronal population guides natural and learned behavior.

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.

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”).

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.