Leonard Khirug group
|Leonard Khirug, PhD
Docent in Neurobiology, Academy Research Fellow
P.O. Box 56, FI-00014 University of Helsinki
Phone: 57644 (internal), +358 45 635 2270
From early development to healthy aging or disease pathogenesis, central nervous system undergoes continuous changes manifested as morpho-functional plasticity of neuronal and glial components of the synaptic networks. While synaptic plasticity has been in the spotlight
of neuroscience for decades, its mechanisms have been studied primarily in reduced preparations. Thus, the relevance of many /in vitro /and /ex vivo /observations remains to be validated within a living organism. Recent developments in photonic and genetic methods are now offering an unprecedented opportunity to study synaptic interactions and signaling
pathways in the highly relevant context of living animal’s brain.
Our group examines the synapse as a tripartite structure composed of a /pre/synaptic neuron (terminal), a /post/synaptic neuron (dendritic spine), and a /peri/synaptic astrocytic process (PAP) that intimately enwraps the other two synaptic components and actively participates in
synaptic function and plasticity. When possible, experiments are carried out either in the intact brain of living animals, but we also use acute brain slices and cultured cells. The palette of our methods includes /in vivo/ two-photon microscopy, intrinsic optical signal imaging, confocal
microscopy, patch clamp electrophysiology, local photolysis of caged compounds, calcium imaging, total internal reflection fluorescence (TIRF) microscopy and a variety of gene manipulation techniques (viral gene delivery, electroporation, transfection and RNA interference). In addition to investigating fundamental physiological mechanisms, we are
studying several pathological models such as stroke, neurodegeneration and brain trauma. Recent highlights from our research are: i) identification of mitochondrial calcium uptake deregulation as the cause of neurodegeneration in neuronal ceroid lipofuscinosis; ii) discovery of an unusually strong temperature dependence of P2X3 receptors offering
mechanistic insights into analgesic effects of cooling; iii) /in vivo /visualization of degeneration and regeneration of nerve endings severed by laser-mediated microsurgery; iv) elucidation of region-specific effects of nitroglycerin on cortical and meningeal vasculature in a rat
model of migraine; v) synthesis and physiological characterization of novel caged agonists for TRPV1 receptors.