Neuroscience

Melville Joseph Wohlgemuth

Assistant Professor, Neuroscience
Member of the General Faculty
Member of the Graduate Faculty
Primary Department
Department Affiliations
Contact
520-621-6640

Work Summary

The Wohlgemuth Lab is focused on how circuits in the brain contribute to sensory-guided adaptive behaviors. The goal is to study how an integrated bottom-up and top-down cortico-fugal network controls behavior on multiple time-scales: from the rapid reactions to arriving sensing information indicative of bottom-up processing, to the longer time-scale governance of categorical behavioral control that is directed by top-down signaling. To study these phenomena, the lab uses the model system of the echolocating bat. The bat provides a way to study how the brain evolved to perform under controlled, laboratory experimentation. To research these questions, the lab employs computer modeling of behavior, multi-channel electrophysiology to relate changes in behavior to changes in brain activity, and optogenetics to test causal hypotheses about the role of different circuit components in sensorimotor integration across time-scales. By combining computational ethology and modeling, electrophysiology, calcium imaging, and optogenetics, the Wohlgemuth Lab offers new insights into circuit-level processing for both rapid control of sensory-guided adaptive behaviors and long-term goal-planning.

Research Interest

The Wohlgemuth Lab was started at University of Arizona in January, 2020. The lab combines computational ethology of natural behaviors, computational modeling of neural data, and multi-channel wireless physiology and optogenetics in freely behaving animals to understand how the brain interacts with the natural environment. Specifically, the lab is focused on the control of the echolocating bat’s natural hunting and navigation behaviors across time-scales as a general model for how the brain receives and reacts to sensory cues under real-world conditions.

Dr. Wohlgemuth’s primary goal as a scientist is to understand how circuits in the brain contribute to natural behaviors for interacting with the world on multiple timescales and dimensions (i.e. azimuth, elevation, and distance). Dr. Wohlgemuth completed his Ph.D. studying the motor control of vocal behaviors, examining how the brain of the bird controls its vocal musculature for the production of song in the laboratory of Dr. Michael Brainard at the University of California, San Francisco. This research involved chronically recording single neuron activity from the vocal motor cortex of the singing bird, relating neuronal activity with the moment-by-moment coding of individual syllables of the bird’s song, as well as overall control of global syllable sequencing. The focus was on how differences in brain activity lead to differences in motor control, and through this research, Dr. Wohlgemuth became very interested in how arriving sensory information is processed to adapt these vocal motor programs. Therefore, as a postdoctoral research Dr. Wohlgemuth chose to work on the echolocating bat because the influence of auditory information on vocal planning is a robust behavior for laboratory studies in this animal.

In his time in Dr. Cynthia Moss’s laboratory as a postdoctoral fellow, Dr. Wohlgemuth completed a variety of related projects investigating dynamic neural activity in relationship to the natural behaviors of the echolocating bat. He studied the superior colliculus (SC) because it sits at the hub of a circuit responsible for processing incoming sensory information about an object’s location into species-specific orienting behaviors. For the bat, this process involves the integration of sonar echo acoustic information into sonar vocalizations as well as adaptive ear and head movements. To research natural, adaptive behavioral control in the echolocating bat, as well as the role of the SC in these sensorimotor processes, Dr. Wohlgemuth completed several projects examining both the behavior of the bat, as well as underlying neural activity in the SC and hippocampus. The first project examined the encoding of the bat’s own sonar vocalizations in the SC. This research determined that the selectivity of auditory neurons in the more superficial sensory layers of the SC was greater than in the deeper, more motor-related layers. Interestingly, auditory selectivity was only found in response to biologically-relevant sounds, with artificial sounds failing to elicit selective responses in the SC. This result points to the importance of neuronal selectivity for sounds related to orientation by sonar, identified signals related to target selection for adaptive motor planning in the SC, and further motivated an ethological approach to understanding brain function.

In addition, Dr. Wohlgemuth also performed several studies evaluating the vocal and body orientation adaptations performed by a bat while it tracks moving prey and navigates through space. These experiments characterized the adaptive planning of signal design (i.e., sonar vocalizations) and signal reception (i.e., head and pinna positioning) for the bat’s active sensing systems. This work found that the bat coordinates adaptive vocal behaviors with movements of the head and ears at millisecond precision with respect, as well as over longer time-frames related to gross target motion. Additionally, this research identified how the bat must simultaneously adapt two motor behaviors (i.e., vocal and postural) in the context of its natural, active-sensing behaviors. The results of these experiments were important for additional projects examining the activity of single neurons in the SC while the bat was engaged in several naturally inspired, acoustic orienting tasks including hunting and spatial navigation behaviors. This work identified sensory, sensorimotor, and motor neurons related to each facet of adaptive sonar behaviors, and interestingly, how the activity of SC neurons is dynamically modified with respect to adaptive changes in the bat’s echolocation behaviors. This research was the first to identify 3D tuning of SC neurons (i.e., azimuth, elevation, and distance) to physical objects in the world, as well as how the spatial tuning of SC neurons sharpen as the bat increases vocal rate, thus increasing the sensory sample rate of its environment. In order to compare results discovered on egocentric tuning of SC neurons, Dr. Wohlgemuth also performed studies on the hippocampus in the echolocating bat to examine allocentric space tuning. This work demonstrated an inverse relationship between the size of hippocampal place fields and the ongoing vocal rate of the bat used to sense the environment. These results demonstrate the importance of studying the brain in a biologically-relevant context: without the bat performing its natural behaviors, it would not have been possible to uncover these novel features of the SC or hippocampus in the context of behaviors for interacting with the natural world.

Current research efforts are focused on how circuits in the brain of the bat contribute to sensory-guided adaptive behaviors. The goal is to study how an integrated bottom-up and top-down cortico-fugal network controls behavior on multiple time-scales: from the rapid reactions to arriving sensing information indicative of bottom-up processing, to the longer time-scale governance of categorical behavioral control that is directed by top-down signaling. The lab employs computational modeling behaviors and multi-channel electrophysiology to relate changes in behavior to changes in brain activity. Additionally, the lab recently developed new technologies of virus injections to both monitor (e.g., calcium imaging) and manipulate (e.g., optogenetics) circuits in the brain of the bat. These efforts will involve existing collaborations with colleagues at Johns Hopkins University (2-photon imaging in Dr. Kishore Kuchibhotla’s Lab), and with members of the Department of Biomedical Engineering at the University of Arizona (Dr. Philipp Gutruf) to develop wireless optogenetic technologies. By combining computational ethology and modeling, electrophysiology, calcium imaging, and optogenetics, the Wohlgemuth Lab will offer new insights into circuit-level processing for both rapid control of sensory-guided adaptive behaviors and long-term goal-planning.

Paulo Pires

Assistant Professor, Physiology
Assistant Professor, Surgery
Member of the General Faculty
Member of the Graduate Faculty
Primary Department
Department Affiliations
Contact
520-626-8632

Work Summary

Dr. Pires is an Assistant Professor and Principal Investigator in the Department of Physiology, University of Arizona College of Medicine Tucson. Dr. Pires received his Ph.D. in Pharmacology and Toxicology at Michigan State University and completed his training as a Postdoctoral Fellow at the University of Nevada, Reno School of Medicine. Throughout his career Dr. Pires has published numerous research articles on the impact of chronic cardiovascular diseases in development of cerebral vascular disorders, such as ischemic strokes, as well as mechanisms regulating cerebral vascular function. In his laboratory, Dr. Pires' research focuses on the vascular component underlying neurodegenerative diseases, such as cerebral amyloid angiopathy and Alzheimer's diseases, as well as the brain waste clearance system, the glymphatic / cervical lymphatic system.

Research Interest

Research in Dr. Pires's laboratory follows his training and expertise in the cerebral microcirculation, and focuses on investigating the role of ion permeable molecular sensors expressed in endothelial cells, both arteriolar and capillary, in the control of localized blood perfusion in the brain, physiologically induced by neuronal stimulation. This interest is coupled with his long-standing scientific passion in elucidating the molecular mechanisms underlying cerebrovascular disorders related to the development of dementia, such as aging, cerebral amyloid angiopathy, Alzheimer's disease and traumatic brain injury. To progress in these projects the Pires lab have developed and is systematically characterizing a mouse strain with endothelial cell-specific knockout of the N-Methyl-D-Aspartate receptor (cdh5:Grin1-/-). Further, the lab has established aging colonies of different mouse models of hypercholesterolemia, cerebral amyloid angiopathy and Alzheimer’s disease, together with respective wild-type littermates, including ApoE3 / ApoE4 knock-in, Tg-SwDI (a model of cerebral amyloid angiopathy), and the 5x-FAD (a model of early-onset Alzheimer’s Disease with prevalence of parenchymal amyloidosis). Further, the Pires lab has a colony of mice expressing the genetically encoded calcium indicator GCaMP8 in endothelial cells (cdh5:GCaMP8), acquired from Dr. Michael Kotlikoff at Cornell University. Lastly, we have successfully implemented AAV-BR1 viral transfection of cerebral endothelial cells using a GFP reporter, we are currently expanding the use of this tool to perform cerebral artery endothelial cells-specific knock-in / knock-out of targets of interest. In recent years the Pires laboratory has started studying the function of the waste clearance system of the brain (the glymphatic system), and its impact and potential therapeutic potential in neurodegenerative diseases. This is an exciting novel area of research involving highly integrative studies, starting at the molecular / cellular signaling level and expanding to whole animal physiology and behavior. Taken together, the long-term goal of the Pires laboratory is to perform translational, clinically relevant scientific investigation of how chronic neurodegenerative diseases, as well as acute traumatic events, affect the cerebral circulation and increase the risk of developing severe dementia, with the hopes of identifying novel therapeutic targets to improve the lives of the affected population.

Julie Elizabeth Miller

Associate Professor, Neuroscience
Associate Professor, Speech, Language, and Hearing Sciences
Primary Department

Work Summary

I am a neuroscientist who studies the impact of aging and neurodegenerative disease on voice and speech. My laboratory seeks a better understanding of the molecules, cells and circuits in the brain that support vocal production.

Research Interest

My laboratory studies neurogenetic mechanisms which underlie normal and abnormal motor speech using the zebra finch songbird. My particular focus is to investigate molecular and cellular pathways altered by speech disorders associated with natural aging and neurological diseases such as Parkinson’s Disease. To carry out these investigations, we use a combination of behavioral, genetic, biochemical and electrophysiological approaches that enable us to link changes at the molecular/cellular levels to alterations in neural circuits for birdsong/human speech. We also have collaborations with researchers working in mouse models to understand shared molecular pathway for vocal function. The end goal is to leverage the advantages offered by each species and an array of biological tools to further advance our understanding of how the brain controls vocalizations. Our laboratory website, including an updated publication list, can be found at: https://julieemiller.lab.arizona.edu/content/publications-abstracts

Charles M Higgins

Associate Professor, Neuroscience
Associate Professor, Neuroscience - GIDP
Associate Professor, Applied Mathematics - GIDP
Associate Professor, Electrical and Computer Engineering
Associate Professor, Entomology / Insect Science - GIDP
Associate Professor, BIO5 Institute
Primary Department
Department Affiliations
Contact
(520) 621-6604

Research Interest

Charles Higgins, PhD, is an Associate Professor in the Department of Neuroscience with a dual appointment in Electrical Engineering at the University of Arizona where he is also leader of the Higgins Lab. Though he started his career as an electrical engineer, his fascination with the natural world has led him to study insect vision and visual processing, while also trying to meld together the worlds of robotics and biology. His research ranges from software simulations of brain circuits to interfacing live insect brains with robots, but his driving interest continues to be building truly intelligent machines.Dr. Higgins’ lab conducts research in areas that vary from computational neuroscience to biologically-inspired engineering. The unifying goal of all these projects is to understand the representations and computational architectures used by biological systems. These projects are conducted in close collaboration with neurobiology laboratories that perform anatomical, electrophysiological, and histological studies, mostly in insects.More than three years ago he captured news headlines when he and his lab team demonstrated a robot they built which was guided by the brain and eyes of a moth. The moth, immobilized inside a plastic tube, was mounted on a 6-inch-tall wheeled robot. When the moth moved its eyes to the right, the robot turned in that direction, proving brain-machine interaction. While the demonstration was effective, Charles soon went to work to overcome the difficulty the methodology presented in keeping the electrodes attached to the brain of the moth while the robot was in motion. This has led him to focus his work on another insect species.

Haijiang Cai

Associate Professor, Neuroscience
Associate Professor, Translational Neuroscience
Associate Professor, Neuroscience - GIDP (
Associate Professor, BIO5 Institute
Member of the General Faculty
Member of the Graduate Faculty
Primary Department
Department Affiliations

Work Summary

Dr. Haijiang Cai's lab studies neural circuitry mechanism of behaviors in health and disease, and develop research tools as well as disease therapies. Recently, the lab has identified specific neural circuits in a brain region called amygdala that play important roles in both emotion and feeding behavior, which could be targeted to treat eating disorders or depression.

Research Interest

Feeding and anxiety are two conserved behaviors critical to survival and health in all mammals. These two behaviors are interacting with each other in health and disease. Patients with abnormal feeding behaviors during eating disorders or obesity are usually associated with anxiety and depression. These two behaviors are controlled by distinct neural circuits distributed across multiple brain regions. However, whether the neural circuits underlying these two behaviors have overlap or interactions is still unknown. The lab of Dr. Haijiang Cai studies the neural circuits of animal behaviors, with a focus on understanding how the neural circuits regulate feeding and emotional behaviors. The recent work from his lab identified a specific population of neurons in the amygdala, a brain region well known for emotion control, also plays important roles in appetite control. His lab is using state-of-the-art optogenetics, chemogenetics, electrophysiology and in vivo microendoscope calcium imaging to dissect the neural circuits. This research will help understand how feeding and anxiety interact with each other, and provide new insight in developing drugs to treat eating and emotional disorders with fewer side effect. Keywords: Neural circuits, Behavior, Feeding, Anxiety

Martha Bhattacharya

Associate Professor, Neuroscience
Faculty Director, Vertically Integrated Projects
Assistant Professor, Neuroscience - GIDP
Assistant Professor, BIO5 Institute
Member of the General Faculty
Member of the Graduate Faculty
Primary Department
Department Affiliations
Contact
(520) 626-3321

Work Summary

We study how neuronal axons and their terminals respond to stress and damage, and how the molecules activated by stress and damage execute decisions about whether to repair themselves or self-destruct. We hope to identify target molecules that could be used to prevent axon and nerve terminal loss in diseases ranging from diabetic neuropathy to Alzheimer's disease.

Research Interest

My work investigates the molecular mechanisms of axon degeneration, a molecular program triggered by toxic, metabolic, or traumatic stress to the axonal compartment of neurons. I use both fruit fly and mouse tools to ask questions about genes involved in axon degeneration and to place these genes in the context of pathways required for axon and synapse maintenance in the face of insults. I have discovered a number of axon degeneration mediators, including MORN4 and TMEM184b as well as others, and am currently following up on their roles within neurons during normal neuronal functioning and in the context of neurodegenerative disorders such as ALS and Alzheimer’s Disease. Keywords: Neurodegeneration, Neurogenetics, Behavior