IPE NINAN, PH.D.
Associate Professor
Office: 105 Block Health Science Building
Tel: 419-383-4126
Email: Ipe.Ninan@utoledo.edu
Education:
2000: Ph.D., Panjab University
2002: Postdoctoral Fellow, Stony Brook University
2007: Associate Research Scientist, Center for Dementia Research/Columbia University
Research Interest:
My Lab is interested in understanding the synaptic and circuit mechanisms underlying
behaviors pertinent to anxiety-and trauma-related symptoms. We study how genetic,
environmental and developmental factors affect the synaptic and intrinsic properties
of neurons in the brain circuits which regulate threat behavior. Our developmental
studies are inspired by the observation that anxiety-and trauma-related symptoms are
elevated during adolescence. Our ongoing studies are focused on understanding how
development-dependent changes in neuromodulation alter synapses in the threat circuitry.
Research Techniques:
Cellular electrophysiology, behavior, imaging, optogenetics and pharmacogenetics.
Research Summary:
1. The BDNF Val66Met polymorphism has been shown to affect both anxiety-like behaviors
and fear extinction, an inhibitory learning involved in regulating anxiety-like symptoms.
Our studies have revealed that the BDNF Val66Met affects NMDA receptor-dependent synaptic
plasticity in the hippocampus, the medial prefrontal cortext and the amygdala, the
three major components of the fear circuit. Our studies have also revealed that the
BDNF Val66Met enhances AMPA receptor-mediated synaptic transmission in the central
amygdala while enhancing glutamate release and NMDA receptor transmission in the dorsal
striatum, suggesting an overactivation of glutamatergic synapses in the subcortical
structures of BDNF Val66Met carriers.
a. Ninan I*, Bath KG, Dagar K, Perez-Castro R, Plummer MR, Lee FS, Chao MV. The BDNF Val66Met polymorphism impairs NMDA receptor-dependent synaptic plasticity in the hippocampus. J. Neurosci. 30: 8866-8870, 2010. *Corresponding author
b. Pattwell SS, Bath KG, Perez-Castro R, Lee FS, Chao MV, Ninan I. The BDNF Val66Met Polymorphism impairs synaptic transmission and plasticity in the infralimbic medial prefrontal cortext. J. Neurosci. 32:2410-21, 2012.
c. Bath KG, Jing DQ, Dincheva I, Neeb CC, Patwell SS, Chao MV, Lee FS, Ninan I. BDNF Val66Met impairs fluoxetine-induced enhancement of adult hippocampus plasticity. Neuropsychopharmacology. 37:1297-304, 2012.
d. Galvin C, Lee FS, Ninan I. Alteration of the centromedial amygdala glutamatergic synapses by the BDNF Val66Met polymorphism. Neuropsychopharmacology 40: 2269-77, 2015.
e. Jing D, Lee FS, Ninan I. The BDNF Val66Met polymorphism enhances glutamatergic transmission but diminishes activity-dependent synaptic plasticity in the dorsolateral striatum. Neuropharmacology 112: 84-93, 2017.
f. Mariga A, Glaser J, Mathias L, Xu D, Xiao M, Worley P, Ninan I, Chao MV. Definition of a bidirectional activity-dependent pathway involving BDNF and Narp. Cell Reports 13:1747-56, 2015.
g. Parkhurst CN, Yang G, Ninan I, Savas JN, Yates JR 3rd, Lafaille JJ, Hempstead BL, Littman DR, Gan WB. Microglia promote learning-dependent synapse formation through brain-derived neurotrophic factor. Cell 155:1596-1609, 2013.
h. Sleiman SF, Henry J, Al-Haddad R, El Hayek L, Abou Haidar E, Stringer T, Ulja D, Karuppagounder SS, Holson EB, Ratan RR, Ninan I, Chao MV. Exercise promotes the expression of brain derived neurotrophic factor (BDNF) through the action of the ketone body β-hydroxybutyrate. Elife 5. pii: el5092, 2016.
2. Our Studies also revealed a development-dependent synaptic plasticity in the basolateral amygdala that contributes to the suppression of fear memory during adolescence. In addition, we demonstrated a development-dependent medial prefrontal cortical synaptic plasticity and its role in the attenuation of fear extinction during adolescence. Specifically, a lack of synaptic plasticity in the adolescent medial prefrontal cortext diminishes fear extinction, which suggests the need for an optimization of treatment strategies for anxiety-like disorders during development.
a. Pattwell SS, Bath KG, Casey BJ, Ninan I*, Lee FS*. Selective early-acquired fear memories undergo temporary suppression during adolescence. Proc. Natl. Acad Sci., 108:1182-1187, 2011. *Co-Corresponding author
b. Pattwell SS, Duhoux S, Hartley CA, Johnson DC, Jing D, Elliott MD, Ruberry EJ, Powers A, Mehta N, Yang RR, Soliman F, Glatt CE, Casey BJ, Ninan I*, Lee FS*. Altered fear learning across development in both mouse and human. Proc. Natl. Acad Sci. 109:16318-23, 2012. *Co-corresponding author
c. Pattwell SS, Liston C, Jing D, Ninan I, Yang RR, Witztum J, Murdock MH, Dincheva I, Bath KG, Casey BJ, Deisseroth K, Lee FS. Dynamic changes in neural circuitry during adolescence are associated with persistent attenuation of fear memories. Nature Communications, 7:11475, 2016.
d. Galvin C, Ninan I. Regulation of the mouse medial prefrontal cortical synapses by endogenous estradiol. Neuropsychopharmacology, 39:2086-2094, 2014.
e. Huang L, Cichon J, Ninan I, Yang G. Post-anesthesia AMPA receptor potentiation prevents anethesia-induced learning and synaptic deficits. Sci Transl Med. 2016 8:344ra85, 2016.
f. Koppensteiner P, Galvin C, Ninan I. Lack of experience-dependent intrinsic plasticity in the adolescent infralimbic medial prefrontal cortex. Synapse. e22090, 2019.
g. Koppensteiner P, Von Itter R, Melani R, Galvin C, Lee FS, Ninan I. Diminished fear extinction in adolescents in associated with an altered somatostatin interneuron-mediated inhibition in the infralimbic cortex. Biological Psychiatry, May 13. pii: S0006-3223(19)31336-8, 2019.
3. In order to better understand the mechanism underlying impaired fear inhibition following aversive events, we have recently initiated studies in the medial habenula-interpeduncular nucleus pathway, which might modulate the classical fear circuitry. These new studies have revealed novel plasticity mechanisms in the medial habenula-interpeduncular nucleus pathway and their involvement in the development-dependent regulation of fear behavior.
a. Koppensteiner P, Galvin C, Ninan I. Development- and experience-dependent plasticity in the dorsomedial habenula. Mol Cell Neurosci. 77:105-112, 2016.
b. Koppensteiner P, Melani R, Ninan I. A cooperative mechanism involving Ca2+-permeable AMPA receptors and retrograde activation of GABAB receptors in interpeduncular nucleus plasticity. Cell Reports, 20:1111-1122, 2017.
c. Melani R, Von Itter R, Jing D, Koppensteiner P, Ninan I. Opposing effects of an atypical glycinergic and substance P transmission on interpeduncular nucleus plasticity. Neuropsychopharmacology, 44:1828-1836, 2019.