Scharfman Lab

Head of Lab

Neuronal plasticity and excitability and their relevance to Neurological
and Psychiatric Disorders

Research led by Helen E. Scharfman, PhD, in the Scharfman Lab, focuses on mechanisms of neuronal plasticity and excitability and their relevance to neurological and psychiatric disorders. Neuronal plasticity in this context is the ability of the nervous system to adapt and change either to improve our memory or other important functions. Neuronal excitability helps maintain our normal functions and support plasticity. However, in disease plasticity and excitability help us adapt and recover. On the other hand, some diseases “hijack” these processes and can actually contribute to the disease, often called maladaptive plasticity. In some diseases excitability is too low or too high, causing impairments in both situations. When high, the term hyperexcitability is often invoked, and is manifested as highly active neurons and even seizures.

Our laboratories mainly use rodents that simulate what occurs in humans, so called animal models of disease. Some of these models involve a mutation that is found in humans, such as some types of Alzheimer’s disease. Other models involve an initial treatment to a normal animal that leads to some of the characteristics of the disease, such as seizures in epilepsy. Our goals are to devise treatments to utilize mechanisms inherent in the brain to reverse maladaptive plasticity and normalize excitability in rodents. Our intent is to develop new therapeutic approaches for humans.

To understand normal mechanisms of plasticity and excitability, we study may aspects of the brain such as the fundamental circuitry. Our focus is on brain areas important to memory and adapting to our environment such as the hippocampus. In the hippocampus there are neurons that are vulnerable to disease in the hilus of the dentate gyrus, so this is one focus. Some of these hilar neurons, such as mossy cells, have been selectively inhibited or excited and we have shown dramatic effects on normal behavior, as well as effects in a mouse model of epilepsy. In the dentate gyrus there are also neurons that are born during adulthood, a phenomenon that is not present in many brain areas. Our work shows that normally adult-born neurons are important to plasticity and help maintain normal excitability, but in disease they have abnormal characteristics that can contribute to the pathology. Our research uses selective suppression or enhancement of these different types of neurons to treat Alzheimer’s disease models or epilepsy models. Our lab also has developed biomarkers in the EEG in these animal models. They occur very early in life, prior to the observation of plaques and tangles, suggesting they will be potentially very helpful as a non-invasive biomarker in humans.

Selected Publications

Botterill JJ, Vinod KY, Gerencer KJ, Teixeira CM, LaFrancois JJ, Scharfman HE. Bidirectional Regulation of Cognitive and Anxiety-like Behaviors by Dentate Gyrus Mossy Cells in Male and Female Mice. J Neurosci. 2021 Mar 17;41(11):2475-2495. doi: 10.1523/JNEUROSCI.1724-20.2021. Epub 2021 Jan 20. PMID: 33472828; PMCID: PMC7984598.
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Botterill JJ, Lu YL, LaFrancois JJ, Bernstein HL, Alcantara-Gonzalez D, Jain S, Leary P, Scharfman HE. An Excitatory and Epileptogenic Effect of Dentate Gyrus Mossy Cells in a Mouse Model of Epilepsy. Cell Rep. 2019 Nov 26;29(9):2875-2889.e6. doi: 10.1016/j.celrep.2019.10.100. PMID: 31775052; PMCID: PMC6905501
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Scharfman HE. The enigmatic mossy cell of the dentate gyrus. Nat Rev Neurosci. 2016 Sep;17(9):562-75. doi: 10.1038/nrn.2016.87. Epub 2016 Jul 28. PMID: 27466143; PMCID: PMC5369357.
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Publications

All publications

Scharfman Lab Members

Chiara Criscuolo, PhD Postdoctoral Researcher 845-398-5437 Chiara.Criscuolo@NKI.rfmh.org	Christos Lisgaras, PhD Postdoctoral Researcher 845-398-5437 Christos.Lisgaras@NKI.rfmh.org	David Alcantara Gonzalez, PhD Postdoctoral Researcher 845-398-5437 David.AlcantaraG@nki.rfmh.org	John LaFrancois Research Scientist 845-398-5437 John.LaFrancois@nki.rfmh.org
Meghan Kennedy Research Support Assistant 845-398-5437 Meghan.Kennedy@nki.rfmh.org