Cellular mechanisms of neurodegeneration, neuroprotection, and repair (in vivo 2P imaging and Brain-computer interfaces)
When we think of brains, we think of neurons. Non-neuronal cells, however, make up more than ten times the population of neurons in the brain. Our research aims to reveal the implications of this huge disparity by determining the principles that govern the roles of non-neuronal brain cells. To date, neural computation remains studied as a purely neuronal process, but that is like trying to solve a puzzle with 10% of the pieces. It will be necessarily insufficient for understanding circuit-level function and dysfunction. Recent results highlight that understanding the role of non-neuronal cells in slowly regulating neural activities could revolutionize our understanding of neural network activity and neurocomputation in neurodegenerative diseases and brain injuries.
The goals of the lab broadly fall into three categories:
(1) Manipulation of neuronal and non-neuronal cells to influence the function of neuronal networks,
(2) Understanding the role of neuroimmune cells in neuronal damage and regeneration, and
(3) Improving long-term performance of implanted electrodes and integrating man-made (engineered) technology with the human brain for the purpose of studying normal and injured/diseased nervous systems in vivo at the cellular level, as well as restoring function to patients.
Therefore, our lab focuses on elucidating biological structures and biochemical pathways that control physiological function and bidirectional communication between the nervous system and neural interface technology. We then apply these newly discovered constraints and possibilities into designing novel technologies and treat neurological conditions. In order to elucidate real-time long-term cellular and molecular tissue interactions to chronically implanted medical devices, we employ in vivo functional electrophysiology, two-photon microscopy, biomaterials, and electrical and optical stimulation techniques. These technologies allow us to advance our understanding of the brain and brain interfaces, as well as create new avenues for diagnosis and treatment of brain pathologies. Ultimately, the goal is to understand how neuronal and non-neuronal cells are integrated in neurocomputation, and understand how to devise targeted intervention strategies for specific neurodegenerative diseases and brain injuries (such as stroke, TBI, Alzheimer's Disease, and Multiple Sclerosis).
Wellman SM, Li L, Yaxiaer Y, McNamara IN, Kozai TDY*. Revealing spatial and temporal patterns of cell death, glial proliferation, and blood-brain barrier dysfunction around implanted intracortical neural interfaces. Frontiers in Neuroscience. 13, 493.
Michelson NJ, Eles JR, Vazquez AL, Ludwig KA, Kozai TDY*. Calcium activation of cortical neurons by continuous electrical stimulation: Frequency-dependence, temporal fidelity and activation density. Journal of Neuroscience Research. 2019. 97(5), 620-638.
Michelson NJ, Kozai TDY*. Isoflurane and Ketamine Differentially Influence Spontaneous and Evoked Laminar Electrophysiology in Mouse V1. Journal of Neurophysiology. 2018. 120(5), 2232-2245.
Wellman SM, Kozai TDY*. In vivo spatiotemporal dynamics of NG2 glia activity caused by neural electrode implantation. Biomaterials. 2018. 164, 121-133. [IF: 8.40]
Michelson NJ, Vazquez AL, Eles JR, Salatino JW, Purcell EK, Williams JJ, Cui XT, Kozai TDY*. Multi-scale, multi-modal analysis uncovers complex relationship at the brain tissue-implant neural interface: New Emphasis on the Biological Interface. J Neural Engineering. 2018. 15, 033001
Eles JR, Vazquez AL, Snyder NR, Lagenaur C, Murphy MC, Kozai TDY*†, Cui XT*†. Neuroadhesive L1 coating attenuates acute microglial attachment to neural electrodes as revealed by live two-photon microscopy. Biomaterials. 2017. 113, 279-292.
Kozai TDY*, Li X, Bodily LM, Caparosa EM, Zenonos GA, Carlisle DL, Friedlander RM, Cui XT*. Effects of caspase-1 knockout on chronic neural recording quality and longevity: Insight into cellular and molecular mechanisms of the reactive tissue response. Biomaterials. 2014. 35(36). 9620-9634
Kozai TDY*, Langhals NB, Patel PR, Deng X, Zhang H, Lahann J, Kotov N*, Kipke DR*. Ultrasmall implantable composite microelectrodes with bioactive surfaces for chronic neural interfaces. Nature Materials. 2012 11(12), 1065-1073. (ToC Image)