I. What are roles of neuronal organelles for synaptic function?
The basic unit of neuronal connectivity, the synapse, is the close apposition between the axonal presynaptic boutons and the postsynaptic dendrite of another neuron (Fig. 1 & 2). Neurotransmitter release is critically regulated by calcium level at presynaptic boutons, and postsynaptically, the temporal and spatial dynamics of calcium influx also plays critical roles in signal transduction and information processing. Therefore, identifying novel mechanisms regulating pre- and/or postsynaptic calcium dynamics in neurons will provide new insights into a wide range of important neurophysiological functions. Previous studies suggested that intracellular organelles like mitochondria and endoplasmic reticulum (ER) control calcium dynamics through their calcium uptake and release properties in various non-neuronal cell types. In addition, recent studies revealed that neuronal ER and mitochondria make contact and functionally interact by transferring calcium (Fig 2 & Video 1). However, their contribution to synapse development and function is still unknown. Our lab is investigating novel roles of intracellular organellar interaction and function for regulation of synapses.
Fig 1. Neurons consist of dendrites and axons and they make synapses, which are the basal units of neuronal connection.
Presynapses along the axon give signals to postsynapses in dendrites of other neurons.
Dendritic ER and mitochondrial Ca2+ dynamics
Fig 2. ER- and mitochondria-dependent calcium regulation in the axon and dendrite. (Edited from Lee et al., Curr. Op. in Physiology, 2018)
Video 1. Dendritic ER-stored calcium can be transferred to the mitochondria upon synaptic stimulation.
II. Can neural circuit properties be determined by intracelluar oraganelles?
Our brain function is orchestrated by various types of neurons and their circuits. Researchers have been endeavoring to unveil mechanisms of neuronal connectivity based on structural and functional properties. However, contribution of subcellular components to neural circuit properties is still not well known. Our lab will expand the knowledge from in vitro studies to the circuit level using various techniques (Fig. 3-5).
Fig 3. in utero electroporation allows us to label intracellular organelles in vivo (Edited from Okada et al., Neurosci. Res., 2007)
Fig 4. Layer II/III cortical pyramidal neurons labelled by in utero elecporation (Tommy Lewis).
Fig 5. Layer II/III cortical pyramidal neuronal mitochondria labelled by in utero elecporation (Tommy Lewis).
Related publications
Hirabayashi Y*, Kwon SK*, Paek H, Pernice W, Paul MA, Lee J, Erfani P, Raczkowski A, Petrey DS, Liza A. Pon LA and Polleux F. (2017)
(* co-first author)
ER-mitochondria tethering by PDZD8 regulates Ca2+ dynamics in mammalian neurons
Science 358, 623–630 (2017)
Kwon SK, Sando R, Lewis TL, Hirabayashi Y, Maximov A and Polleux F. (2016)
PLoS Biology. 14(7):e1002516 (2016)
Lee A*, Hirabayashi Y*, Kwon SK*, Lewis TL* and Polleux F. (2018) (*co-first author)
Emerging roles of mitochondria in synaptic transmission and neurodegeneration
Curr. Op. in Physiol. (2018)
Kwon SK, Hirabayashi Y and Polleux F. (2016)
Organelle-specific sensors for monitoring Ca2+ dynamics in neurons
Front. Synaptic Neurosci. doi: 10.3389/fnsyn.2016.00029