Laboratory of Cellular and Molecular Regulation National Institute of Mental Health NIMH

Brain network mechanisms of visual perceptual organization in schizophrenia and bipolar disorder. Invasive human neural recording links resting-state connectivity to generation of task activity. As a PhD candidate she received a NIH F31 fellowship for her thesis work which examined the role of the innate immune response and KlAnnLabNyu.org cell death mechanisms in Traumatic Brain Injury induced pulmonary dysfunction.

Poster at the Organization for Human Brain Mapping (OHBM) conference, Glasgow, Scotland, UK. 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.

Elegans as a model to interrogate axon response to traumatic injury. She was an Alfred P. Sloan Fellow and a recipient of the NSF-PECASE award and the NINDA Javits Award. Schultz D., Ito T., Solomyak L., Chen R., Mill R., Kulkarni K., Cole M.W.

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. Alzheimer's disease is the most common neurodegenerative disease and it is the most common underlying cause of dementia. Our research seek to delineate the cellular processes that lead to the network dysfunction and the endogenous clearing mechanism of oligomers. Answering this question will guide the development of even more efficient delivery strategies, bringing the promise of mRNA-based treatments for Alzheimer’s, Parkinson’s and other brain diseases closer to reality. In a new paper in Nano Letters, the researchers demonstrate how peptides — short strings of amino acids — can serve as precise targeting molecules, enabling LNPs to deliver mRNA specifically to the endothelial cells that line the blood vessels of the brain, as well as neurons.

The other major development in cellular and molecular neuroscience has been the ability to study good animal models of human disease, often using mutants and genetic variants, and even with direct study of humans using cellular and molecular methods. My own research has moved to the direct study of humans, albeit using epidemiologic approaches. It is striking that of the manuscripts is this anniversary issue, most are models of hypertension, stroke, Alzheimer’s disease, glaucoma, spinal cord injury, and menopause. There are several manuscripts focused on COVID-19 infection and some using human stem cells. This movement to study human disease as directly as possible is a very positive development.

John Disterhoft LabStudying the neurobiology of associative learning in the mammalian brain

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.

Research Conducted at NIMH (Intramural Research Program)

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.

The laboratory’s mission is to better understand the causes and mechanisms of brain tumors, such as glioblastomas, in order to provide more individualized treatment to patients today and develop innovative therapies for these aggressive cancers in the future. 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. 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.

Sanchez-Romero R, Chen R, Lalta N, Ito T, Mill RD, Cole MW (November 2023). Rapid learning to automaticity reveals learned content stored within patterns of resting-state functional connectivity changes Poster at the Society for Neuroscience Annual Meeting, Washington, DC. The Molecular Neuroscience and Neuro-Oncology Laboratory is an innovative research laboratory that connects the latest in research with clinical practice, and is dedicated to staying at the forefront of brain tumor research.