UCR

Molecular, Cell and Systems Biology



Viji Santhakumar


viji
Office: (951) 827-2010
Fax: (951) 827-3087
1308 Spieth Hall
Office Hours: , 2pm - 3pm
Email: vijayalakshmi.santhakumar@ucr.edu

Viji Santhakumar, Ph.D.

Associate Professor
Ph.D., 2003, University of California, Neuroscience
MBBS, 1994, Kilpauk Medical College, Clinical Medicine

Biography

Research Interest: Our lab seeks to identify the cellular and synaptic mechanisms of epilepsy following brain injury and unprovoked seizures. We adopt a powerful combination of electrophysiological, molecular and immunohistological techniques with computational modeling to analyze the pathophysiological processes underlying long-term morbidity in epilepsy and after mild concussive brain injury. Our major focus is in identifying hippocampal inhibitory circuit plasticity in epilepsy. Using technically challenging recordings from interneuronal pairs, we have identified intrinsic synaptic and non-synaptic plasticity of dentate basket cells after seizures and adopted computational modeling to determine the functional consequences of these changes. Our studies in experimental models of epilepsy have revealed complex cell-type specific changes in inhibitory networks that affect network oscillations. In parallel my lab studies mechanisms of acquired epilepsy after traumatic brain injury.  Our studies span multiple aspects of post-traumatic pathology from the nature of impact to neuro-immune interactions underlying long-term cognitive dysfunction. Our studies have revealed differential effects of slow-rate, concussive versus rapid, blast-like TBI on cellular damage and neurological outcome. We recently identified that certain class of immune receptors (toll-like receptors, TLRs) and enhanced dentate neurogenesis contribute to early post-injury dentate hyperexcitability and development of epilepsy. We are currently examining neuroimmune interactions in post-traumatic pathology and translational potential for therapeutic interventions targeting TLRs and neurogenesis.  

Publications

 

  1. Neuberger EJ, Gupta A, Subramanian  D,  Korgaonkar AA,  Santhakumar, V (2017) Converging early responses to brain injury pave the road to epileptogenesis. J.Neurosci.Res, doi: 10.1002/jnr.24202.
  2. Veerasammy S, Kumari E, Goodus MT,  Neuberger EJ, , Santhakumar V  and Levison SW  (2017) . Consequences of Inflammation Within Neural Stem Cell Niches On Development And Regeneration In The Immature Brain. 2nd edition of the Frontiers in Stem Cell and Regenerative Medicine research e-Book, edited by Drs. Atta-Ur-Rahman and Anjum. Vol.7, 43-91.
  3. Neuberger EJ, Swietek B, Corrubia L, Prasanna A, Santhakumar, V.(2017) Enhanced Dentate Neurogensis after Brain Injury Undermines Long -Term Neurogenic Potential and Promotes Seizure Susceptibility. Stem Cell Reports 2017 Sep 12;9(3):972-984. doi: 10.1016/j.stemcr.2017.07.015.
  4. Subramanian, D, Santhakumar, V (2017). Lighting the Fuse: Deconstucting Complex Network Interactions Using On-Demand Seizures. Epilepsy Currents Invited Commentary, May-Jun;17(3):174-176.
  5. Swietek, B., Gupta, A., Proddutur, A., Santhakumar, V.(2016) Immunostaining of Biocytin-filled and Processed Sections for Neurochemical Markers. J. Vis. Exp. (118), e54880, doi:10.3791/54880.
  6. Gupta, A, Santhakumar, V (2016). Illuminating the Role for Chloride Dysregulation in Network Activity. Epilepsy Currents, Jul-Aug;16(4):258-260.
  7. Abdul-Muneer PM, Long M, Conte AA, Santhakumar V, Pfister BJ, (2016). High Ca2+ influx during traumatic brain injury leads to Caspase-1-Dependent neuroinflammation and cell death. Molecular Neurobiology. DOI:10.1007/s12035-016-9949-4.
  8. Murugan M, Santhakumar V, Kannurpatti S (2016). Activation-induced spatiotemporal cerebral blood flow changes and behavioral deficit after mTBI in immature rats can be favorably altered by facilitating mitochondrial calcium uptake. Frontiers in Systems Neuroscience. DOI: 10.3389/fnsys.2016.00019.
  9. Proddutur A, Santhakumar V (2016). Fingerprints of interictal spikes: Can imprints deliver a verdict on their role in epilepsy? Epilepsy Currents. Jan-Feb;16(1):41-2. DOI: 10.5698/1535-7597-16.1.41.
  10. Yu J, Swietek B, Proddutur A, Santhakumar V (2016). Dentate cannabinoid-sensitive interneurons undergo unique and selective strengthening of mutual synaptic inhibition in experimental epilepsy. Neurobiology of Disease. Jan, 21; 89:23-35. DOI:10.2016/j.nbd.2016.01.013.
  11. Proddutur A, Santhakumar V (2015). Marching towards a Seizure: Spatio-temporal Evolution of Preictal activity., Epilepsy Currents.Sep-Oct; 15(5): 267–268.
  12. Yu J, Proddutur A, Swietek B, Elgammal F, Santhakumar V (2015). Functional reduction in Cannabinoid-Sensitive Heterotypic Inhibition of Dentate Basket Cells in Epilepsy: Impact on Network Rhythms. Cerebral Cortex. DOI: 10.1093/cercor/bhv199.
  13. Wahab RA, Neuberger EJ, Lyeth BG, Santhakumar V, Pfister BJ (2015)., Percussion Injury Device for the Precise Control of Injury Parameters. Journal of Neuroscience Methods. Jun 15; 248:16-26. DOI: 10.1016/j.jneumeth.2015.03.010.
  14. Yu J, Swietek B, Proddutur A, Santhakumar V, (2015)., Dentate total molecular layer interneurons mediate cannabinoid-sensitive inhibition. Hippocampus. Aug;25(8):884-9. DOI: 10.1002/hipo.22419.
  15. Li Y*, Korgaonkar A*, Swietek B, Wang J, Elgammal FS, Elkabes, S,Santhakumar V (2015). Toll-like receptor 4 augments mossy cell AMPA currents and contributes to NMDA receptor-independent increase in dentate excitability after brain injury. Neurobiology of Disease. DOI: 10.1016/j.nbd.2014.11.021* Equal Contribution.
  16. Pang KCH, Sinha S, Avcu P, Roland JJ, Nadpara N, Pfister BJ, Long M, Santhakumar V, Servatius RJ. (2014)., Long-lasting suppression of acoustic startle response following mild traumatic brain injury. Journal of Neurotrauma. DOI:10.1089/neu.2014.3451.
  17. Ordek G, Proddutur A, Santhakumar V, Pfister BJ, Sahin M (2014)., Electrophysiological Monitoring of Injury Progression in the Rat Cerebellar Cortex. Frontiers in Systems Neuroscience Oct 9;8:197. DOI: 10.3389/fnsys.2014.00197. eCollection 2014.
  18. Neuberger EJ*, Abdul Wahab R, Jaykumar A, Pfister BJ, SSanthakumar V (2014)., Distinct effect on impact rise times on immediate and early neuropathology after brain injury in juvenile rats. Journal of Neuroscience Research. 05 May 2014.
  19. Proddutur A*, Yu J, Elgammal FS, Santhakumar V (2013)., Seizure-induced alterations in fast-spiking basket cell GABA currents modulate frequency and coherence of gamma oscillation in network simulations. Chaos. 20 November. 23, 046109.
  20. Santhakumar V, Pratap M*, Karakossian MH*, Otis TS (2013)., A reinforcing circuit action of extrasynaptic GABA(A) receptor modulators on cerebellar granule cell inhibition. PLOS ONE 2013 Aug 19;8(8):e72976.
  21. Yu J*, Proddutur A*, Elgammal FS, Ito T, Santhakumar V (2013)., Status epilepticus enhances tonic GABA currents and depolarizes GABA reversal potential in dentate fast-spiking basket cells. The Journal of Neurophysiology 109: 1746-1763. Also featured in Global Medical Discovery.
  22. Gupta A, Elgammal FS*, Proddutur A*, Shah S, Santhakumar V (2012)., Decrease in Tonic Inhibition Contributes to Increase in Dentate Semilunar Granule Cell Excitability after Brain Injury. The Journal of Neuroscience 32(7): 2523-2537.Also featured in Psychology Progress
  23. Santhakumar V, Jones RT., Mody I (2010)., Developmental Regulation and Neuroprotective Effects of Striatal Tonic GABAa Currents. Neuroscience 167(3):644-55.
  24. Santhakumar V (2008), Modeling mossy cell loss and mossy fiber sprouting in epilepsy In: Computational Neuroscience in Epilepsy edited by Soltesz I and Staley K.J. Academic Press. 89-111.
  25. Morgan R, Santhakumar V, Soltesz I (2007), Modeling the Dentate Gyrus In: The Dentate Gyrus edited by Scharfman H. Elsevier press. Progress in Brain Research 163C:639-658.
  26. Santhakumar V, Wallner M, Otis TS, (2007)., Ethanol acts Directly on Extrasynaptic Subtypes of GABAa Receptors to Increase Tonic Inhibition. Alcohol 41(3):211-221.
  27. Dyhrfjeld-Johnsen J*, Santhakumar V*, Morgan R, Huerta R, Tsimring L, Soltesz I (2007). Topological Determinants of Epileptogenesis in Large-Scale Structural and Functional Models of the Dentate Gyrus Derived from Experimental Data. Journal of Neurophysiology 97(2):1566-1587.
  28. Santhakumar V, Hanchar HJ, Wallner M, Olsen RW & Otis TS (2006)., Contributions of the GABAA Receptor Subunit a6 to Phasic and Tonic Inhibition Revealed by a Naturally Occurring Polymorphism in the a6 Gene. Journal of Neuroscience 26(12):3357 –3364.
  29. Santhakumar V, Aradi I, Soltesz I (2005)., Role of Mossy Fiber Sprouting and Mossy Cell Loss in Hyperexcitability: A Network Model of the Dentate Gyrus Incorporating Cell Types and Axonal Topography. Journal of Neurophysiology 93(1):437-53.
  30. Aradi I*, Santhakumar V*, Soltesz I (2004)., Simple Rules Govern the Impact of Heterogeneous Perisomatic IPSC Populations on Pyramidal Cell Firing Rates. Journal of Neurophysiology 91: 2849–2858.
  31. Santhakumar V and Soltesz I (2004) Heterogeneity on the Move: Plasticity of Interneuronal Species Diversity and Parameter Variance in Neurological Diseases. Trends in Neuroscience 27(8):504-10.
  32. Ratzliff AH, Howard A, Santhakumar V, Osapay I, Soltesz I (2004)., Rapid Deletion of Mossy Cells Does Not Result in a Hyperexcitable Dentate Gyrus: Implications for Epileptogenesis. Journal of Neuroscience 24(9):2259 –2269.
  33. Santhakumar V, Voipio J, Kaila K, Soltesz I (2003). Post-traumatic hyperexcitability is not caused by impaired buffering of extracellular potassium. Journal of Neuroscience 23(13):5865-76.
  34. Aradi I, Santhakumar V, Chen K, Soltesz I (2002)., Postsynaptic effects of GABAergic synaptic diversity: regulation of neuronal excitability by changes in IPSC variance. Neuropharmacology 43: 511-522.
  35. Chen K, Aradi I, Santhakumar V, Soltesz I (2002) H-channels in epilepsy: new targets for seizure control? Trends in Pharmacological Sciences 23: 552-557.
  36. Ratzliff AH, Santhakumar V, Howard A, Soltesz I (2002) Mossy cells in epilepsy: rigor mortis or vigor mortis? Trends in Neuroscience 25: 140-144.
  37. Santhakumar V, Ratzliff AD, Jeng J, Toth K, Soltesz I (2001). Long-term hyperexcitability in the hippocampus after experimental head trauma. Annals of Neurology 50: 708-717.
  38. Santhakumar V, Bender R, Frotscher M, Ross ST, Hollrigel GS, Toth Z, Soltesz I (2000)., Granule cell hyperexcitability in the early post-traumatic rat dentate gyrus: the 'irritable mossy cell' hypothesis. Journal of Physiology (London) 524 Pt 1: 117-134.

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