Toborek Lab Miller School of Medicine

He was an Alfred P. Sloan Fellow, a two-time recipient of the McKnight Technological Innovations in Neuroscience Award, a recipient of the NINDS Javits Award and a recipient of the Siegel Family Award for Outstanding Biomedical Research. Dissociation of anterior cingulate, dorsolateral prefrontal, and fronto-polar cortex during a visual search task reveals specialized roles within a commonly activated fronto-parietal network. Independent and distributed coding of task-set decision rules within prefrontal cortex. In our research we seek connectivity-based explanations of neurocognitive phenomena, especially those related to learning and goal-directed cognition. She started her faculty position at The Miami Project to Cure Paralysis at the University of Miami Miller School of Medicine in 2022, where she currently investigating mechanisms of systemic organ dysfunction after Central Nervous System injury.

In particular, how are these interactions flexibly reconfigured when animals make decisions that use different underlying computations? To do this we combine high-throughput mouse behavior in virtual reality, optical and genetic tools to measure and manipulate the dynamics of single neurons and neuronal populations, and computational approaches to understand both the behavior and its relationship to neural activity. 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. The main research interest in my laboratory is focused on the vascular effects of HIV infection with the focus on the alterations of the blood-brain barrier (BBB). My laboratory is recognized for studies on the integrity and functions of the BBB and was first to describe dysfunction of brain endothelial cells in response to methamphetamine (METH) and potentiation of the BBB disruption when exposure to METH and HIV proteins is combined.

Current studies demonstrate that composition of mRNPs is dynamic across space and time. The generation of new reagents, such as transgenic mice expressing PP7 stem-loops knocked-in to the 3′UTR of the activity-regulated gene Arc, offers a promising tool to address in vivo how neuronal activity regulates local proteomes. The main action in the generation of neuronal proteome diversity remains in the nucleus. Soto and Lipscombe review recently publications on the cellular mechanisms that regulate alternative splicing, highlighting the specific action of select RNA splicing factors in regulating neuronal membrane protein isoforms. They also discuss how the mechanistic dissection of the SMN (Survival of Motor Neuron) protein in alternative splicing leads to the development of therapeutic strategies in treating human patients. 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. Our research in the area of cellular and molecular neuroscience covers a broad spectrum of approaches to understand the functions and dysfunctions of specific molecules and cell types in the brain and spinal cord.

• Simulated comparisons of slow and rapid event-related task-based functional connectivity.
• He carried out postdoctoral work at Stanford University in the department of Molecular and Cellular Physiology.
• We are excited to apply our skill and experience in an academic environment that encourages out-of-the box thinking to find ever more advanced ways to help patients.
• The initial detection of a given neurotransmitter on the postsynaptic dendrite is usually handled by ionotropic receptors, assembled into complexes that determine the precise localization and turnover of these ion channels.
• She received her BS with honors in Cell Biology at Peking University and her PhD in Molecular Biology at University of California, Berkeley.

At that time, there were many laboratories focused on the biochemistry of the nervous system, but that wasn’t really “molecular” neuroscience. Tissue culture of other types of cells was common, but there were extra challenges growing nerve cells in culture. The manuscripts published in volume 1 of Cellular and Molecular Neurobiology were primarily electrophysiologic reports, some studies of tissue culture of hybrid neurons or glia, and biochemical measurements of transmitter substances in various nervous tissues. It is interesting to look at the manuscripts in this issue, most of which are the study of molecular mechanisms in the nervous system. While there are still questions that are best addressed using electrophysiologic and cellular methods, most current research questions require more molecular approaches.

Network Disruptions Underlying Brain Disorders and Aging

Harvard’s diverse neuroscience community — hundreds of basic researchers and physician-scientists, are engaged in the process of discovery across campuses and disciplines in Cambridge and the Greater Boston Area. Three major nodes are the Department of Neurobiology at Harvard Medical School, the Center for Brain Science (CBS) at the Faculty of Arts and Sciences in Cambridge and the F.M. Sex hormonal releases have a significant effect on sexual dimorphisms (phenotypic differentiation of sexual characteristics) of the brain. Recent studies seem to suggest that regulating these dimorphisms has implications for understanding normal and abnormal brain function. Sexual dimorphisms may be significantly influenced by sex-based brain gene expression which varies from species to species.

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.

Neurocognitive Basis of Cognitive Control

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.

Molecular neuroscience is a branch of neuroscience that observes concepts in molecular biology applied molecular neuroscience laboratory to the nervous systems of animals. 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.