publicATIONS

 

RECENT OR IN PRESS


Scharfman HE (2016) The enigmatic mossy cells of the dentate gyrus. Nat Rev Neurosci 17:562-575. PMID 27466143. 


Sex differences in area CA3 pyramidal cells. Special Issue, Journal of Neuroscience Res. 95: 563-575. PMID 27870399.


Mendell AI, Atwi S, Bailey CD, McCloskey DP, Scharfman HE, MacLusky NJ (2017)Expansion of mossy fibers and CA3 apical dendritic length accompanies the fall in dendritic spine density after gonadectomy in male, but not female, rats. Brain Struct Funct,  222:587-601. PMID 27283589.

This paper follows a physiological study of gonadectomized rats that showed surprising expansion of mossy fibers and increased mossy fiber synaptic responses after gonadectomy in males (Skucas et al, 2013 see “BDNF” page). The Golgi staining described in the present study showed that the expansion of mossy fibers is also robust by Golgi staining and consistent with the physiology. In addition, gonadectomized females did not show these changes.


Drew LJ, Kheirbek MA, Luna VM, Denny CA, Cloidt MA, Wu MV, Jain S, Scharfman HE, Hen R. (2016) Activation of local inhibitory circuits in the dentate gyrus by adult-born neurons. Hippocampus. 26:763-778.

This paper showed that normal adult born granule cells have remarkably inhibitory effects on mature granule cells when they are young, meaning 6-7 weeks or less. The results were collected using a validated transgenic mouse line that expressed channelrhodopsin in nestin-expressing precursors to granule cells upon injection of tamoxifen. Mature granule cells were patched in slices made 6-7 weeks after tamoxifen and blue light pulses were used to activate young granule cells. In addition, in vivo data showed that blue light led to less c-fos immunoreactivity in granule cells than control conditions. The results are consistent with the idea that young granule cells help keep dentate granule cells from being too active.  In addition they suggest that young granule cells, if abnormal, could cause disinhibition in the dentate gyrus which is consistent with the studies of Iyengar et al (2015) and Cho et al (2015). [See Neurogenesis page, Epilepsy page).

http://www.ncbi.nlm.nih.gov/pubmed/26662922


Kam K, Duffy AM, LaFrancois JJ, Scharfman HE (2016) Interictal spikes during sleep are an early defect in the Tg2576 mouse model of β-amyloid neuropathology. Sci. Rep. 6:20119. doi: 10.1038/srep20119.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4730189/

This paper showed that the earliest sign of hyperexcitability in mouse models of Alzheimer’s disease are interictal spikes in sleep. Two models used animals that have overexpression and mutation in amyloid precursor protein (APP) and additional studies were done in a mouse model of Down’s syndrome where individuals usually develop Alzheimer’s disease. The results suggest a new biomarker for the early stages of sleep and new possibilities for therapeutics.


Blackstad JS, Osen KK, Scharfman HE, Storm-Mathisen J, Blackstad TW, Leergaard TB (2015) Observations on hippocampal mossy cells in mink (Neovision vision) with special reference to dendrites ascending to the granular and the molecular layers. Hippocampus.

In press

This paper brings together some of data acquired by Theodor Blackstad that was never published.  It addresses the characteristics of mossy cells in the mink, a species that was possible to study in Oslo, where Blackstad worked in the last part of his career.


Scharfman HE, Myers CE (2015) Corruption of the dentate gyrus by “dominant” granule cells: Implications for dentate gyrus function in health and disease. Neurobiol. Learn Mem Special Issue.

In press

This paper discusses the empirical and computational evidence that neurons may become excessively activated and synaptic inputs and outputs sufficiently potentiated that they dominate pathways, leading to impairments in behavior and possibly seizures.


Scharfman HE, Bernstein HL (2015) Potential implications of a monosynaptic pathway from mossy cells to adult-born granule cells of the dentate gyrus. Frontiers Syst Neuroscience Special Issue. 9:112

http://www.ncbi.nlm.nih.gov/pubmed/26347618


Scharfman HE.(2015) Neuroscience. Metabolic control of epilepsy. Science. 347:1312-3.

http://www.ncbi.nlm.nih.gov/pubmed/25792315


Cho KO, Lybrand ZR, Ito N, Brulet R, Tafacory F, Zhang L, Good L, Ure K, Kernie SG, Birnbaum SG, Scharfman HE, Eisch AJ, Hsieh J. (2015) Aberrant hippocampal neurogenesis contributes to epilepsy and associated cognitive decline. Nat Commun. 6:6606.

http://www.ncbi.nlm.nih.gov/pubmed/25808087

This paper provides the first evidence that abnormal neurogenesis in epilepsy is a therapeutic target. By preferentially ablating these cells, seizures were reduced in an animal model of epilepsy.


D'Amour J, Magagna-Poveda A, Moretto J, Friedman D, LaFrancois JJ, Pearce P, Fenton AA, MacLusky NJ, Scharfman HE (2015) Interictal spike frequency varies with ovarian cycle stage in a rat model of epilepsy. Exp Neurol. 269:102-119.

http://www.ncbi.nlm.nih.gov/pubmed/?term=Scharfman%2Cd'amour

This study shows that female rats have cyclic increases in excitability after a modified procedure to induce epilepsy.  Furthermore, use of an estrogen receptor antagonist could stop the cyclic increases in excitability. The implications are discussed with respect to disorders in women where cyclic increases in excitability occur, such as catamenial epilepsy.