We are combining electrophysiological, imaging and behavioral techniques to investigate the cellular, molecular and systems mechanisms underlying normal and pathological auditory processing.
Our recent studies are focusing on the role of zinc as a novel neurotransmitter in the brain and its role on auditory processing.
Another area of our current research focuses on tinnitus and its underlying cellular and molecular mechanisms. Based on our recent findings on the molecular mechanisms underlying the induction of tinnitus and in collaboration with the medicinal chemist Dr. Peter Wipf of the University of Pittsburgh, we are developing and testing novel specific Kv7.2/3 (KCNQ2/3) activators for preventing the triggering of tinnitus. Moreover, our current tinnitus-related studies are aimed towards understanding the neuronal mechanisms that underlie the maintenance of tinnitus.
Selected Recent Publications
Anderson CT, Kumar M, Xiong S, Tzounopoulos T (2017). Cell-specific gain modulation by synaptically released zinc in cortical circuits of audition. Elife. 2017 Sep 9;6. pii: e29893. doi: 10.7554/eLife.29893. [Epub ahead of print]
Kalappa BI, Tzounopoulos T (2017). Context-Dependent Modulation of Excitatory Synaptic Strength by Synaptically Released Zinc. eNeuro. 2017 Mar 3;4(1). pii: ENEURO.0011-17.2017. doi: 10.1523/ENEURO.0011-17.2017. eCollection 2017 Jan-Feb.
Ankur Joshi, Bopanna I. Kalappa, Charles T. Anderson and Thanos Tzounopoulos (2016). Cell-Specific Cholinergic Modulation of Excitability of Layer 5B Principal Neurons in Mouse Auditory Cortex. Journal of Neuroscience, 2016 Aug 10;36(32):8487-99.
Kumar M, Reed N, Liu R, Aizenman E, Wipf P, Tzounopoulos T (2016). Synthesis and Evaluation of Potent KCNQ2/3-specific Channel Activators. Mol Pharmacol. 2016 Mar 22. pii: mol.115.103200.
Li S., Kalappa B.I, and Tzounopoulos T (2015) Noise-Induced Plasticity of KCNQ2/3 and HCN Channels Underlies Vulnerability and Resilience to Tinnitus. Elife 2015;10.7554/eLife.07242.
Bopanna I. Kalappa, Heun Soh, Kevin Duignan, Takeru Furuya, Scott Edwards, Anastassios V.Tzingounis and Thanos Tzounopoulos (2015). Potent KCNQ2/3-specific channel activator suppresses in vivo epileptic activity and prevents the development of tinnitus. Journal of Neuroscience, 2015 Jun 10;35(23):8829-42.
Anderson C.T, Radford R.J, Zatsrow M.L, Zhang D.Y, Apfel U, Lippard S.J, and Tzounopoulos T (2015). Modulation of Extrasynaptic NMDA Receptors by Synaptic and Tonic Zinc. Proc Natl Acad Sci USA (PNAS), 2015 May 6. pii: 201503348.
Tamara Perez-Rosello, Charles T. Anderson, Cindy Ling, Thanos Tzounopoulos (2015). Tonic Non-Vesicular Zinc Inhibits Spontaneous Neuronal Firing in Dorsal Cochlear Nucleus Principal Neurons by Enhancing Tonic Glycinergic Inhibition. Neurobiology of Disorder, 2015 Mar 18. pii: S0969-9961(15)00084-4. doi: 10.1016/j.nbd.2015.03.012. [Epub ahead of print].
Ankur Joshi, Jason Middleton, Charles T. Anderson, Katharine Borges, Benjamin Suter, Gordon M. G. Shepherd and Thanos Tzounopoulos (2015). Cell-specific, activity-dependent fractionation of layer 2/3→5B excitatory signaling in mouse auditory cortex. Journal of Neuroscience, 2015 Feb 18;35(7):3112-23.
Li S., Choi V., and Tzounopoulos T (2013). Pathogenic Plasticity of Kv7.2/3 Channel Activity is Essential for the Induction of Tinnitus. Proc Natl Acad Sci USA (PNAS), 2013 June 11; 110 (24) 9980-9985.
Perez-Rosello T., Anderson C., Schopfer F., Zhao Y., Gilad D., Salvatore S., Freeman B., Hershfinkel M., Aizenman E., and Thanos Tzounopoulos (2013). Synaptically Released Zn2+ Inhibits Neurotransmitter Release by Promoting Endocannabinoid Synthesis. Journal of Neuroscience, 2013 May 29;33(22):9259-72).
Leao RM, Li S, Doiron B, Tzounopoulos T (2012). Diverse levels of an inwardly rectifying potassium conductance generate heterogeneous neuronal behavior in a population of dorsal cochlear nucleus pyramidal neurons. Journal of Neurophysiology, 2012 Jun;107(11):3008-19.
Doiron B, Zhao Y, Tzounopoulos T (2011). Combined LTP and LTD of Modulatory Inputs Controls Neuronal Processing of Primary Sensory Inputs. Journal of Neuroscience, 2011 Jul 20;31(29):10579-92.
Jason W. Middleton,Taro Kiritani, Courtney Pedersen, Jeremy Turner, Gordon M. G. Shepherd, Thanos Tzounopoulos (2011). Mice with Behavioral Evidence of Tinnitus Exhibit Dorsal Cochlear Nucleus Hyperactivity Due to Decreased GABAergic Inhibition. Proc Natl Acad Sci USA (PNAS), 2011 May 3;108(18):7601-6.
Yanjun Zhao and Thanos Tzounopoulos (2011). Physiological Activation of Cholinergic Inputs Controls Associative Synaptic Plasticity via Modulation of Endocannabinoid Signaling. Journal of Neuroscience, 2011 Mar 2;31(9):3158-68
News and Views Articles on Our Work
Biochemistry (2018): New Tools Uncover New Functions for Mobile Zinc in the Brain.
Elife (2017): A new role for zinc in the brain.
NSF (2017): NSF-BSF-supported Study Turns Up the Volume on the Mysteries of Sound
University of Pittsburgh (2016): Sound Investment: Pitt, Allergan to Collaborate on Tinnitus Research
UPMC/University of Pittsburgh (2016): Pitt Team Redesigns Epilepsy Drug to Increase Potency and Specificity, Reduce Side Effects
Molecular Pharmacology Highlights (2016): MOL Highlight: Synthesis and Evaluation of Potent KCNQ2/3-Specific Channel Activators
Expert Opin Ther Targets (2015): Potassium channels as promising new targets for pharmacologic treatment of tinnitus: Can internet-based "crowd sensing" initiated by patients speed up the transition from bench to bedside?
UPMC/University of Pittsburgh (2015): Pitt Team Identifies Cause of Resilience to Tinnitus, Drugs That Can Reduce Chance of Developing the Debilitating Condition
Pittsburgh Post-Gazette (2015): University of Pittsburgh finds zinc to be important in brain signaling
Science and Technology Daily (2015): New Drug to Quiet Brain, Relieving Epilepsy and Tinnitus
SciFluor (2015): Novel KCNQ2/3 activator
The Eye and Ear Foundation of Pittsburgh (2015): Stop The Ringing
The Science Business eXchange(2013): Potassium channel Kv7.2 (KCNQ2); KCNQ3
The Hearing Journal (2013): Noise-Induced Tinnitus Linked to Lower Potassium Channel Activity
Εθνικός Κήρυξ (2013): Θα σώσει εκατομμύρια η έρευνα του Θάνου Τζουνόπουλου
NIH/NIDCD (2013): Grantee news, Pitt team finds biologic mechanism that causes noise-induced tinnitus and drug that can prevent it.
Journal of Neuroscience (2013): This Week in The Journal
Department of Defense (2013): Mechanisms Underlying Noise-Induced Tinnitus
Wall Street Journal (2011): Finding the Pathways to a Cause of Tinnitus
Voice of America (2011): Research Shows Tinnitus May Affect Brain Responses
National Public Radio (2011): Study Finds Cause for Tinnitus
Science Daily (2011): Tinnitus Caused by Too Little Inhibition of Brain Auditory Circuits