Cellular and Molecular Neuroscience
Our research in this area covers a broad spectrum of approaches to understand the functions and dysfunctions of specific molecules and cell types in the brain and spinal cord. Ongoing studies by department faculty are revealing molecular/cellular mechanisms in a variety brain regions including basal ganglia, spinal cord, neocortex, and hippocampus, and in both normal and pathological states, particularly Parkinson’s disease, chronic pain, and neurodevelopmental disorders. A major theme is ion channels and electrophysiology.
Defining the principles underlying the normal and abnormal operation of the basal ganglia
Research Description
Our research focuses on the basal ganglia, a group of subcortical brain nuclei that are critical for voluntary movement, learning and motivation, and the primary site of dysfunction in psychomotor disorders such as Parkinson's disease, Huntington's disease, obsessive-compulsive disorder and addiction. Our objectives are to define the principles underlying the normal and abnormal operation of the basal ganglia. Our hope is that this information will provide the foundation for the rational development of therapies that more effectively treat the symptoms or underlying causes of these disorders.
We utilize multiple experimental approaches including electrophysiology, 2-photon imaging, anatomical and molecular profiling, and viral vector-based techniques including optogenetics, pharmacogenetics and knockdown of synaptic receptors and ion channels. Our research is supported by the National Institute for Neurological Disorders and Stroke and the Cure Huntington's Disease Initiative.
For lab information and more, see Dr. Bevan's faculty profile and lab website.
Publications
See Dr. Bevan's publications on PubMed.
Contact
Contact Dr. Bevan at 312-503-4828.
Lab Staff
Research Faculty
Postdoctoral Fellows
Graduate Students
Visiting Scholar
Understanding the cellular and molecular building blocks of basal ganglia macrocircuit
Research Description
Neurodegenerative diseases
To date, millions of people in the US suffer from neurodegenerative diseases. Current therapeutic strategies are limited, short-lived, and ineffective. Our research seeks to provide the mechanisms that underlie the pathogenesis of Alzheimer's Disease, Parkinson’s disease, and Huntington’s Disease. We hope to translate our insights into developing novel treatments for these neurological disorders.
Alzheimer's disease is the most common neurodegenerative disease and it is the most common underlying cause of dementia. It affects primarily the cortex and hippocampus. Severe synapse loss and inclusions can be observed. Our research seek to delineate the cellular processes that lead to the network dysfunction and the endogenous clearing mechanism of oligomers.
Parkinson’s disease and Huntington’s disease are the two major neurodegenerative diseases that affect the motor function. Our research interests center on better understanding the cellular and molecular building blocks that make up the basal ganglia macrocircuit as well as their implications in both health and disease.
Inter-cell communications
An effective communication in the brain involves proper controls of how signals are generated, how they are terminated, and how they are spatiotemporally distributed. This process involves a complex architecture of ion channels, receptors, synapse, release and clearance machinery, etc. Our lab studies how this is achieved and how it is altered in disease conditions. The main focus is on intrinsic excitability, neurotransmission, and their regulation by astrocytes.
Multidisciplinary approach
Using cell-population transcriptomic analysis as a guide, a more effective and targeted electrophysiological analyses can be devised. The combination cell-specific Cre-driver lines, Cre-responsive transgenic mice and viral constructs forms a very powerful research tool that will allow us to tackle difficult research question that would not be otherwise possible.
Our research is currently funded by the NINDS, NIA/CNADC, DoD, PDF, NMF, APDA, and CHDI.
For lab information and more, see Dr. Chan's faculty profile and lab website.
Publications
See Dr. Chan's publications on PubMed.
Contact
Contact Dr. Chan at 312-503-1146 or the lab at 312-503-1146.
Lab Staff
Lab Manager
Postdoctoral Fellows
Suraj Cherian, Qiaoling Cui, Daniela Garcia, Harry Xenias
Graduate Students
Technical Staff
Brianna Berceau, Nicole Curtis, Morgan Marshall
Visiting Scholar
Undergraduate Students
Seeking to understand the link between synaptic dysfunction and neuropsychiatric disorders and neurodevelopmental disorders
Research Description
Research in our laboratory is directed at understanding the mechanisms of synaptic transmission and plasticity and the role that glutamate receptors have in brain function and pathology. We use a multidisciplinary approach including in vitro electrophysiological recording, optogenetics, cellular imaging, mouse behavior and biochemical techniques. We ultimately seek to understand the link between synaptic dysfunction and neuropsychiatric disorders and neurodevelopmental disorders. Current projects are investigating altered synaptic signaling in mouse models of obsessive compulsive disorder, schizophrenia and fragile X syndrome.
For lab information and more, see Dr. Contractor's faculty profile or lab website.
Publications
See Dr. Contractor's publications on PubMed.
Contact
ContactDr. Contractor 312-503-1843 or the lab at 312-503-0276.
Lab Staff
Research Faculty
Postdoctoral Fellows
Qionger He, Toshihiro Nomura, Shintaro Otsuka
Graduate Students
John Marshall, Olga Melendez-Fernandez, Chad Morton, Christine Remmers, Yiwen Zhu
Technical Staff
We study the neurobiology of associative learning in the mammalian brain at the molecular, cellular and systems levels using both in vivo and in vitro techniques. Our laboratory focuses on characterizing how neurons store new information during associative learning. An important component of our research program is identifying mechanisms for altered learning in aging. We use a combination of behavioral, biophysical and molecular biological approaches to address these questions.
Research Description
Eyeblink conditioning is our primary model paradigm to assess associative learning. This Pavlovian task offers excellent stimulus control, ease of precise behavioral measurement, robust associative learning, and can be used to test both human and non-human animal subjects. We study rabbits, rats, mice, or humans depending upon the question being asked. We also use a broad set of additional techniques, including fear conditioning, spatial navigation in the Morris water maze and others, to assess other types of behavior to evaluate the specificity of experimental manipulations on mechanisms of associative learning.
Our program focuses on characterizing the ways in which neurons store new information during associative learning at the cellular and subcellular levels. Experiments focus on the hippocampus, a paleocortical region involved in transferring information during learning from the short- to long-term memory store. We make biophysical measurements from hippocampal brain slices taken from eyeblink-trained animals to define what ionic mechanisms underlie the changes in neuronal excitability recorded in the intact animal. An important focus of our research is on cellular mechanisms for altered learning in aging. Recently, we have incorporated calcium-imaging techniques using both a charge-coupled device (CCD) camera system and a two-photon laser scanning microscopy (2P-LSM) system to investigate learning- and aging-related changes in calcium properties in CA1 pyramidal neurons.
Our laboratory conducts multiple-single neuron recording experiments using chronically implantable microdrives in rabbits as they perform eye blink conditioning, an associative memory task. We take advantage of an integrated approach combining several techniques such as paired recordings from anatomically identified neurons, optogenetic, immunohistochemistry, light and electron microscopy applied to wild-type and transgenic animals. We use these techniques to test hypotheses about the neurophysiological properties and the functional role of neurons from brain regions that are involved in associative memory such as the prefrontal cortex, hippocampus, thalamus, and the basal ganglia.
Magnetic resonance imaging permits examination of the entire brain simultaneously and observation of changes in brain activity in the same individual over time. Functional magnetic resonance imaging is being done in rabbits with our collaborators Daniel Procissi and Lei Wang.
For lab information and more, see Dr. Disterhoft's faculty profile and lab website.
Publications
See Dr. Disterhoft's publications on PubMed.
Contact
Contact Dr. Disterhoft at 312-503-7982 or the lab at 312-503-3112.
Lab Staff
Research Faculty
Postdoctoral Felow
Graduate Students
Carmen Lin, Amy Rapp, Matthew Schroeder, Xiao-Wen Yu
Technical Staff
Anna Marisa Di Staulo, Mellissa Grana, Mary Kando, Michael McCarthy, Quinn Smith
Temporary Staff
Identifying and investigating novel molecular bases of cellular recognition that govern neuronal circuit assembly during human development and disease.
Research Description
Developing neurons integrate into functional circuits through a series of cell recognition events, which include neuronal sorting, axon and dendrite patterning, synaptic selection, among others. Our research focuses on cell-surface recognition molecules that mediate interactions between neurons to discriminate and select appropriate targets in the developing brain. Additionally, we seek to uncover novel mechanisms of neural recognition that lead to brain connectivity defects in humans. To explore the broader roles for cell recognition molecules and their pivotal function in neural circuit development, our lab takes advantage of a battery of modern laboratory techniques. These approaches include animal and stem cell disease modeling, as well as next-generation sequencing and CRISPR/Cas9 gene editing. Identifying fundamental principles of cellular recognition in wiring circuits contributes to our understanding of neurological disorders and how neuronal dysfunction arises from aberrations during development of the human brain.
For lab information and more, see Dr. Guemez-Gamboa's faculty profile and lab website.
Publications
See Dr. Guemez-Gamboa's publications on PubMed.
Contact
Contact Dr. Guemez-Gamboa at 312-503-0752.
Lab Staff
Postdoctoral Fellow
Nadya Gabriela Languren, Jennifer Rakotomamonjy
Technical Staff
Investigating the mechanisms of motor output the spinal cord in both normal and disease states
Research Description
Neurons in the spinal cord provide the neural interface for sensation and movement. Our lab focuses on the mechanisms of motor output in both normal and disease states (spinal injury, amyotrophic lateral sclerosis). We use a broad range of techniques including intracellular recordings, array recordings of firing patterns, 2-photon imaging, pharmacological manipulations, and behavioral testing. These techniques are applied in in vitro and in vivo animal preparations. In addition we have extensive collaborations with colleagues who study motor output in human subjects.
For lab information and more, see Dr. Heckman's faculty profile.
Publications
See Dr. Heckhman's publications on PubMed.
Contact
Contact Dr. Heckman at 312-503-2164.
Lab Staff
Research Faculty
Mingchen Jiang, Michael Johnson, Katharina Quinlan, Thomas Sandercock
Postdoctoral Fellows
Graduate Students
Seoan Huh, Edward Kim, Christopher Mullens, Emily Reedich, Theeradej Thaweerattanasinp, Jessica Wilson
Technical Staff
Exploring the synaptic- and circuit-level mechanisms underlying the generation and dissemination of neurmodulatory information in the brain
Research Description
Early studies into the neuromodulatory information encoded by midbrain dopamine neurons suggested that a key function of dopamine is to transmit reward prediction error signals - a measure of whether events were better or worse than expected based on previous experience. However, not all midbrain dopamine neurons appear to encode similar information in their activity patterns. For example, our research has shown that substantia nigra dopamine neurons differ in their responses to aversive stimuli depending on their projection target, a finding that comports with previous literature on heterogeneous dopamine firing patterns and further suggests that diversity in the dopamine system can be best understood in the context of specific circuits and behaviors. Building on this investigative framework, we are now working to correlate individual variability in dopamine-related behaviors with detailed structural and functional connectivity observations within the midbrain dopamine system. By using natural sources of variability in mouse behavior, we gain access to study the potentially large yet unexplored natural range of individual variation in the circuit organization of the midbrain dopamine system. By simultaneously obtaining whole-brain anatomical and functional neural circuitry datasets, we hope to build a comprehensive theory of how specific individual differences in the circuitry of the heterogeneous midbrain dopamine system support a diverse set of behaviors, including reinforcement learning, motivation, risk preference and addiction.
For lab information and more, see Dr. Lerner's faculty profile and lab website.
Publications
See Dr. Lerner's publications on PubMed.
Contact
Contact Dr. Lerner.
Lab Staff
Technical Staff
Investigating the neuronal circuits that underlie the functions of the hippocampus
Research Description
Our laboratory investigates the neuronal circuits that underlie the functions of the hippocampus, which is a region of the brain involved in learning and memory.
In particular, we are interested in the roles played by specific cell types such as GABAergic interneurons and Cajal-Retzius cells in regulating network synchronization, synaptic plasticity, and in guiding the correct development of the hippocampal structural and functional architecture.
Our goal is to discover novel synaptic mechanisms that are of physiological relevance, but may also provide original insights for the pathogenesis of neurological diseases such as epilepsy and neurodevelopmental disorders, which often target the hippocampus.
We take advantage of an integrated approach combining several techniques such as paired recordings from anatomically identified neurons, optogenetic, immunohistochemistry, light and electron microscopy applied to wild-type and transgenic animals.
For lab information and more, see Dr. Maccaferri's faculty profile.
Publications
See Dr. Maccaferri's publications on PubMed.
Contact
Contact Dr. Maccaferri at 312-503-4358.
Lab Staff
Graduate Student
Technical Staff
Researching mechanisms of neuronal excitability and organization of brain microcircuits
Research Description
The lab has two main research lines: mechanisms of neuronal excitability and organization of brain microcircuits.
We pursue these two wide basic science interests by investigating scientific questions with immediate potential for bench to bed translation. In particular, altered neuronal excitability is involved in important pathologies such as epilepsy, neurodegenerative diseases and neuropathic pain. Similarly, understanding the local brainstem networks that underlie the generation and regulation of breathing is a necessary step to understanding the mechanisms of SIDS (Sudden Infant Death Syndrome). Finally, we are interested in the identification of the role of unipolar brush cells, a recently discovered cell type of the cerebellar cortex, in cerebellar microcircuits.
To investigate these questions we use multiple techniques such as electrophysiological recordings from neurons and dendrites in brain slices and cultures, PCR analysis of gene expression, histochemical analysis of protein expression and optogenetic manipulations.
For lab information and more, see Dr. Martina's faculty profile.
Publications
See Dr. Martina's publications on PubMed.
Contact
Contact Dr. Martina at 312-503-4654.
Lab Staff
Research Faculty
Postdoctoral Fellows
Graduate Students
Visiting Scholars
Studying the molecular and cellular mechanisms that control the formation and modification of dendritic spines in the mammalian brain
Research Description
Research in my laboratory centers on the molecular and cellular mechanisms that control the formation and modification of dendritic spines in the mammalian brain. These mechanisms underlie the normal development and plasticity of the brain, and contribute to higher brain functions, including cognitive, social, and communication behavior. However, when these mechanisms go awry, they lead to mental and neurological disorders. Our analysis integrates multiple organizational levels, from molecular, cellular, circuit, and rodent models, to human subjects. We employ both a “translational” strategy, utilizing basic mechanistic data we generate to understand disease pathogenesis, and a “reverse-translational” strategy, in which genetic, neuropathological, and imaging studies in human subjects help guide the discovery of novel mechanistic insight. The ultimate goal of these studies is to develop therapeutic approaches to prevent or reverse neuropsychiatric disorders, by targeting mechanisms that control dendritic spines and synapses.
Projects within Our Lab
1. Mechanistic studies on the molecular mechanisms of dendritic spine plasticity. This line of research aims to identify and elucidate functions of novel molecular regulators of synaptic circuit modification during the lifespan. We investigate the formation, remodeling, and elimination of spiny synapses in neurons using both in vitro and in vivo models. We are particularly interested in signaling, adhesion, and scaffolding molecules that control cell-to-cell communication and mediate intracellular signaling by neurotransmitter receptors. My laboratory continues to investigate small GTPase pathways and the roles of guanine-nucleotide exchange factors, such as kalirin and Epac2, and their downstream targets Rac, PAK, Rap and Ras. In addition, we have made important contributions to understanding how synaptic activity controls synapse size and strength through a pathway involving NMDA receptors, CaMKII, kalirin, Rac1 and actin, how rapid synaptic plasticity in the brain is regulated by locally synthesized estrogen, how adhesion molecules including N-cadherin control synapse size and strength, and how dopamine and neuroligin control synapse stability though Epac2 and Rap1.
2. Translational and reverse-translational studies on the molecular substrates of dendritic spine pathology. Investigations of genetic, neuropathological, and neuromorphological alterations in human subjects with psychiatric disorders have started to reveal the pathogenic mechanisms behind these illnesses, and are also guiding the discovery of unexpected basic mechanisms of brain development and function. Through studies performed in the lab and through collaborations, we investigate molecular and cellular alterations occurring in patients with schizophrenia, bipolar disorder, autism, and Alzheimer’s disease. We then use model systems, such as neuronal cultures or mice, to elucidate the functions and pathogenic mechanisms of key molecules. We are currently investigating the basic synaptic functions of several leading mental disorder risk genes, to understand how they contribute to normal brain function and to synapse pathology. Conversely, many molecules we have been studying in the lab have more recently been implicated in the pathogenesis of mental disorders through independent neuropathological or genetic studies. We have shown that molecules that control basic synapse structural plasticity, such as kalirin and Epac2, functionally interact with leading mental disorder risk molecules, such as neuregulin1, ErbB4, DISC1, 5HT2A receptors, dopamine receptors, neuroligin, and Shank3. We have generated mutant mice in which kalirin or Epac2 are ablated, and have shown that these molecules control behaviors relevant for mental disorders, such as sociability, working memory, sensory motor gating, and vocalizations. These animal models can thus help to understand the synaptic substrates of specific aspects of mental disorders. To investigate the abnormal regulation of these molecular pathways in schizophrenia, autism, Alzheimer’s disease, and the impact of these molecular abnormalities on disease phenotypes in human subjects, we are collaborating with neuropathologists, brain imaging experts, and geneticists who investigate human subjects.
Potential Clinical Implications of Our Work
Therapeutic reversal of neuropsychiatric disease by targeting synaptic connectivity. By harnessing the knowledge from our basic and reverse-translational studies, my goal is to develop novel therapeutic approaches to prevent, delay, or reverse the course of mental and neurodegenerative disorders. Because abnormal synaptic connections play central roles in the pathogenesis of schizophrenia, autism, and Alzheimer’s disease, pharmacological targeting of key molecules implicated in synaptic plasticity and pathology can rescue disease associated abnormalities, and thereby influence the outcome of the disease. We are currently developing transgenic animal models to validate synaptic signaling molecules as therapeutic targets in mental disorders. We are also developing cellular assays which we will use in high-throughput screens for small-molecule regulators of synapse remodeling. Our goal is to identify small-molecule regulators of synapse remodeling which can be taken into clinical trials as therapeutics aimed at reversing synaptic deficits, and thus cognitive dysfunction, in mental disorders.
Our Facilities
In our studies, we employ a multidisciplinary approach, using an array of methods that include advanced cellular and in vivo microscopy, biochemistry, electrophysiology, manipulations of gene expression in vivo, mouse behavioral analysis, circuit mapping, and human genetics and neuropathology.
For lab information and more, see Dr. Penzes's faculty profile and lab website.
Publications
See Dr. Penzes's publications on PubMed.
Contact
Contact Dr. Penzes at 312-503-5379.
Lab Staff
Postdoctoral Fellows
Daniel Bermingham, Lorenza Culotta, Marc Forrest, Maria Dolores Martin de Saavedra, Kristoffer Myczek, Euan Parnell, Nicolas Piguel, Christopher Pratt, Marc Dos Santos, Sehyoun Yoon, Colleen Zaccard
Graduate Students
Technical Staff
Leonardo Dionisio, Katherine Horan, Daniel Loizzo
Visiting Scholar
Temporary Staff
Applying multiple tools of quantitative synaptic circuit analysis to elucidate the functional ‘wiring diagrams’ of neocortical neurons in the mouse motor cortex
Research Description
Synaptic circuits in motor areas of neocortex engage in neural operations underlying many aspects of cognition and behavior – motor control, executive functions, working memory, and more – yet circuit organization at the synaptic, cellular, and molecular levels remains poorly understood in agranular cortex. What is the functional organization of these synaptic pathways? What cellular and circuit-level operations do neurons in these perform? How do these local circuits communicate with each other and how do they interact with subcortical systems in the basal ganglia and thalamus? The focus of our laboratory is to apply multiple tools of quantitative synaptic circuit analysis to elucidate the functional ‘wiring diagrams’ of neocortical neurons in motor cortex. We use laser scanning photostimulation (LSPS) microscopy, based on glutamate uncaging and channelrhodopsin-2 excitation, for rapid functional mapping of synaptic pathways onto single neurons in brain slices of motor cortex. We are also applying a variety of circuit analysis tools in efforts to identify circuit-level mechanisms in mouse models of disease, including autism, Rett syndrome, epilepsy, and motor neuron diseases.
For lab information and more, see Dr. Shepherd’s faculty profile and lab website.
Publications
See Dr. Shepherd's publications on PubMed.
Contact
Contact Dr. Shepherd at 312-503-1342 or the lab at 312-503-0753.
Lab Staff
Postdoctoral fellows
John Barrett, Xiaojian Li, Naoki Yamawaki
Graduate student
Visiting Scholar
Understanding the principles of neuronal dysfunction in disease states
Research Description
Our group has five research topics. The first topic area is what drives Parkinson’s disease (PD). Using a combination of optical, electrophysiological and molecular approaches, we are examining the factors governing neurodegeneration in PD and its network consequences, primarily in the striatum. This work has led to a Phase III neuroprotection clinical trial for early stage PD and a drug development program targeting a sub-class of calcium channels. The second topic area is network dysfunction in Huntington’s disease (HD). Using the same set of approaches, we are exploring striatal and pallidal dysfunction in genetic models of HD, again with the aim of identifying novel drug targets. The third topic area is striatal dysfunction in schizophrenia, with a particular interest in striatal adaptations to neuroleptic treatment. The fourth topic area is post-traumatic stress disorder and the role played by neurons in the locus ceruleus in its manifestations. The last topic area is chronic pain states and the impact these have on the circuitry of the ventral striatum.
For lab information and more, see Dr. Surmeier's faculty profile.
Publications
See Dr. Surmeier's publications on PubMed.
Contact
Contact Dr. Surmeier at 312-503-4904.
Lab Staff
Research Faculty
Michelle Day, Jaime Guzman-Lucero, Jyothisri Kondapalli, David Wokosin, Weixing Shen, Zhong Xie
Postdoctoral Fellows
Yijuan Du, Patricia Gonzalez Rodriguez, Steven Graves, Ema Ilijic, Harini Lakshminarasimhan, Austin Lim, Stephen Logan, Tristano Pancani, Tamara Perez-Rosello, Kristen Stout, Asami Tanimura, Cecilia Tubert, Sasha Ulrich, Enrico Zampese, Shenyu Zhai
Graduate Students
Daniel Galtieri, Alexandria Melendez, Ben Yang
Technical Staff
Marisha Alicea, Kang Chen, Yu Chen, Kyle Dombeck, Bonnie Erjavec,Christine Kamide, Danielle Schowalter
Visiting Scholar
Examining the neural control of movement, focusing on the role of spinal circuitry
Research Description
We use an interdisciplinary approach in this research, using a combination of behavioral, biomechanical, and neurophysiological techniques. Our current research examines the neural control of internal joint variables, evaluating the hypothesis that the nervous system actively regulates the stresses and strains within joints in order to minimize injury. We examine this issue using biomechanics, characterizing how muscles affect the stresses and strains within joints; using behavioral studies, characterizing how the CNS adapts kinematics and muscle activations to compensate for alterations in joint structures; and using electrophysiological studies, examining the neural systems involved in regulating joint stresses and strains.
We are also developing neuroprostheses for restoring functional movements following spinal cord injury. This is collaborative work with Dr. Lee Miller. Previous work from his lab has shown the potential of cortically controlled FES: using cortical predictions of muscle activation to drive stimulation of paralyzed muscles, thereby restoring natural control of a paralyzed animals’ own limb. We are developing these procedures in a rodent model, examining whether this approach can be used to restore the hindlimb movements underlying locomotion in animals paralyzed by spinal cord injury.
For lab information and more, see Dr. Tresch's faculty profile.
Publications
See Dr. Tresch's publications on PubMed.
Contact
Contact Dr. Tresch at 312-503-1373.