Research Projects

ABSTRACT The taste of food is a critical factor that determines whether an organism will accept or reject a food source. In addition, the sensory perception of food taste changes significantly depending on the metabolic state of animals. Despite the significant progress in understanding the homeostatic biology of food intake in the mammalian brain, how metabolic states (e.g., how hungry an animal is) alter the perception of food taste at the level of specific neuronal circuits remains poorly understood.

Project Summary The brain uses sensory representations to assess risk and predict reward in order to adjust behavior. Per­ ception is a multisensory process. To make reliable predictions, it is advantageous for the brain to combine more than one sensory modality to represent the world. In humans, as in many species, there is evidence for sophisticated forms of learning, such as crossmodal enhancement, where the integration of multiple stimuli from different modalities facilitates memory formation and/or improves discrimination.

Assessing social signals, such as vocalizations, figures prominently in the outcome of aggressive encounters, including the potential to win a fight or prevent escalation resulting in physical injury. Among vertebrates, the neural circuitry integrating sensation, for example what an individual hears, with modulation of aggressive output, is distributed throughout the forebrain and conserved across vertebrate lineages. Social behavior is thought to be an emergent property of activity across this network, and audition plays a prominent role in modulating aggression in primates and birds.

Despite the fact that visual perception represents such a fundamental aspect of our everyday life, our knowledge of the underlying neural coding of natural stimuli is woefully lacking. One major limitation preventing our understanding of the neural underpinnings of natural vision is the lack of viable methodologies for recording and synchronizing eye movements and incoming visual stimuli from freely-moving monkeys during unrestrained exploratory behavior.

The neuromodulators acetylcholine (ACh) and norepinephrine (NE) are associated with an activated cortical brain state characterized by an increase in the reliability of cortical responses to external stimuli and enhanced performance on behavioral tasks. A key unresolved question is the spatial and temporal scale at which these neuromodulators exert their effects. New methods to directly record the local availability of ACh and NE simultaneously with the activity of neural populations in mice opens up the possibility to answer this question.

Project Summary Electrical microstimulation has become a mainstay of fundamental neuroscience exploration and an increasingly prevalent clinical therapy. Despite the growing prevalence of neuromodulation therapies, the fundamental physiological and mechanistic properties driving the beneficial effect for the patient are poorly understood. This R01 application aims to greatly improve our understanding of how different non-neuronal cells (myeloid lineage, oligodendrocyte progenitor lineage, and vascular smooth muscle cells) respond and contribute to the electrical stimulation response.

Project Abstract The application of electric stimulation (ES) to the brain has been widely used to perturb the physiological and pathological dynamics of neuronal circuits, with established applications including therapeutic interventions for neurological disorders such as epilepsy, dementia, and Parkinson’s disease. However, the biophysical mechanisms underlying ES in the brain remain unclear. There is still a lack of understanding about where, when, and how to apply ES to brain circuits in vivo.

Project Summary Intracranial electrical brain stimulation (EBS) remains a central method in the clinic as well as for research in several animal model systems. However, little is actually known about the ensembles of neurons activated by typical and clinical intracranial EBS protocols. These stimulation protocols often require a trial-and-error learning period (during and after invasive neurosurgery) to determine what stimulation parameters are effective, if any at all are effective.

Abstract: Our goal is to develop a cellular level understanding of how transcranial magnetic stimulation (TMS) may activate neurons in the human cerebellum (Cb) using (i) electrophysiological measurements in an in vitro turtle Cb, (ii) computational modeling of the induced electric (E) fields in the tissue and (iii) an MEG-EEG-TMS human saccade study. Since the local microanatomy and electrophysiology of the Cb are evolutionarily conserved from reptiles to man, it is likely that the fundamental neural dynamics will generalize.

Project Summary Transcranial current stimulation (TCS) creates small electrical fields in the brain through electrodes placed on the scalp. As a method for neuromodulation, TCS carries with it many practical benefits: it is portable (battery- operated), inexpensive, and easily deployable in the clinic and at home.