Research Interest

• Current Research Interests and ongoing projects in the lab:

1.  Cell-type specific neuromodulation of synaptic transmission and network connectivity by neuromodulators.

2. Species comparison for the characteristics of short-term synaptic dynamics from mouse and non-human primate to human cortical neurons.

3. Frequency based synaptic filtering in small network depending upon their short-term synaptic dynamics.

• Contribution to Science (so far)

1. Translational approaches for the characterization of synaptic connectivity and short-term plasticity between cortical neurons of Human and non-human primates (NHP).  My recent scientific contribution has been focused on studying synaptic connectivity and short-term plasticity between molecularly defined neuron types in human cortical circuitry from resected surgical tissues. To this end, we were able to characterize local synaptic connectivity and their synaptic dynamics (i.e., 10, 20, 50 Hz presynaptic spike frequencies with 8 pulses and various recovery intervals up to a few seconds) between supragranular pyramidal neurons and neighboring interneurons. As a result, we found overall synaptic physiology characteristics between excitatory and neighboring interneurons found in mouse sensory cortex, was conserved to the human associate cortex with a few differences. This work was recently published in ELife (Kim et al., 2023). In parallel, this approach has been expanded to the NHP tissues with collaboration of Washington National Primate Research Center’s (WaNPRC) Tissue Distribution Program (TDB) at the University of Washington. NHP tissues are from macaques (Macaca mulatta, Macaca nemestrina) or squirrel monkey (Simia sciurea). We combined AAV-based viral labeling by either in vivo injection or in vitro infection of PVALB or chandelier cell enhancers. Currently, this work is under preparation of Journal submission. I think this approach provides us not only to design our cellular and synaptic physiological studies in a cell type-specific way but also to compare existing human and rodent data.

·         Kim, M.H.* et al. (2023). Target cell-specific synaptic dynamics of excitatory to inhibitory neuron connections in supragranular layers of human cortex. ELife 12, e81863, [* first and corresponding author].

·         Campagnola, L., Seeman, S.C., ..., Kim, M.H., et al. (2022). Local connectivity and synaptic dynamics in mouse and human neocortex. Science 375, eabj5861. doi: 10.1126/science.abj5861.

·         Berg, J., Sorensen, S.A., Ting, J.T., Miller, J.A., ..., Kim, M.H., et al. (2021). Human cortical expansion involves diversification and specialization of supragranular intratelencephalic- projecting neurons. Nature 598, 151-158.

2. Subnetworks synaptic connectivity and their function in mammalian cortex. In the cerebral cortex, the interaction of excitatory and inhibitory synaptic inputs shapes the responses of neurons to sensory stimuli, stabilizes network dynamics and improves the efficiency and robustness of the neural code. To better understand the roles of synaptic connectivity and strengths between excitatory and inhibitory neurons, we combined in vivo function calcium imaging in awake mouse, and post-hoc ex vivo synaptic connectivity measurements with multiple whole-cell patch-clamp recordings. In this study, we found that although parvalbumin-expressing (PVALB) inhibitory cells, as a key player of E-I balance, in mouse primary visual cortex make connections with the majority of nearby pyramidal cells, the strength of their synaptic connections is structured according to the similarity of the cells’ responses (Znamenskiy*, Kim*, Muir* et al., 2024; * equal contribution). In parallel, to address one of fundamental questions such as the connectivity rules by which neurons in neocortex choose their synaptic partners, the relationship between recurrent synaptic connectivity within an area and their long-range projection target has been investigated. In sensory cortex, intermingled neurons encode different attributes of sensory inputs and relay them to different long-range targets. This study found that, although the response properties of layer 2/3 neurons projecting to different targets were often similar, they avoided making connections with each other (Kim*, Znamenskiy* et al., 2018).

·         Znamenskiy, P.*, Kim, M.H.*, Muir, D.R.*, Iacaruso, M.F., Hofer, S.B., Mrsic-Flogel, T. (2024). Functional selectivity of recurrent inhibition in visual cortex. Neuron 112, 1-10 [* equal contribution].

·         Lee, J.H., Kim, M.H., Vijayan, S. (2020). Temporal learning of bottom-up connections via spatially nonspecific top-down inputs. Neurocomputing 411, 128-138.

·         Kim, M.H.*, Znamenskiy, P.*, Iacaruso, M.F., Mrsic-Flogel, T. (2018). Segregated subnetworks of intracortical projection neurons in primary visual cortex. Neuron 100, 1313-1321 [* equal contribution].

3. Synaptic transmission, plasticity and their developmental changes in retinal circuits.  I have studied information processing at synapses in retinal microcircuits. Specifically, my research has been focused on studying the synaptic physiology between bipolar cells (excitatory interneurons) and amacrine cells (inhibitory inter­neurons). Interestingly, a novel form of Ca2+-dependent postsynaptic plasticity in some populations of amacrine cells, which are aspiny interneurons in the inner retina, was observed. This observation leads to investigate the mechanism, and this study discovered that local Ca2+ rises through Ca2+-permeable AMPA receptors on the amacrine cell dendrites are crucial for the initiation of a novel type of long-term plasticity. This study may contribute significantly to our understanding of the role of inhibitory interneurons in slow light adaptation processes in the early visual system (Kim et al., 2016). Furthermore, the developmental changes of the ribbon synapse between rod bipolar cells (RBC) and AII-amacrine cells in the mouse retina had been studied. This study shows that both evoked EPSCs and light-evoked currents in AII-amacrine cells are composed of a fast, transient component and a slower sustained component. During development, the slow sustained component of the EPSC increased and the onset delay became shorter, even though the amplitude of presynaptic Ca2+ currents in the RBCs did not change significantly. With quantal deconvolution analysis, our results support the idea that the pool size and release probability increase during development after eye opening (Kim et al., 2023).

·         Kim, M.H.*, Strazza Jr., P., Puthussery, T., Gross, O.P., Taylor, W.R., von Gersdorff, H. (2023). Functional maturation of the rod bipolar to AII-amacrine ribbon synapse in the mouse retina. Cell Rep. 42, 113440, doi:10.1016/j.celrep.2023.113440 [* first and corresponding author].

·         Kim, M.H., von Gersdorff, H. (2016). Postsynaptic plasticity triggered by Ca2+-permeable AMPA receptor activation in retinal amacrine cells. Neuron 89, 507-520.

·         Balakrishnan, V., Puthussery, T., Kim, M.H., Taylor, W.R., von Gersdorff, H. (2015). Synaptic vesicle exocytosis at the dendritic lobules of an inhibitory interneuron in the mammalian retina. Neuron 87, 563-575.

·         Kim, M.H., Li, G.L, von Gersdorff, H. (2013). Single Ca2+ channels and exocytosis at sensory synapses. J. Physiol. 591, 3167-3178.

·         Vickers, E., Kim, M.H., Vigh, J., von Gersdorff, H. (2012). Paired pulse plasticity in the strength and latency of light-evoked lateral inhibition to retinal bipolar cell terminals. J. Neurosci. 32, 11688-11699.

·         Kim, M.H., Vickers, E., von Gersdorff, H. (2012). Patch-clamp capacitance measurements and Ca2+ imaging at single nerve terminals in retinal slices. J. Vis. Exp. 59, pii: 3345. doi:10.3791/3345.

·         Kim, M.H., von Gersdorff, H. (2010). Extending the realm of membrane capacitance measurements to nerve terminals with complex morphologies. J. Physiol. 588, 2011-2012.

4. Signal transduction and calcium dependent exocytosis in epithelial and neuroendocrine cells. My earliest work was to study signal trans­duction pathways of protease-activated receptor 2 (PAR-2), a novel and recently discovered G-protein coupled receptor. We were able to demonstrate that the endogenous receptor expressed in pancreatic duct epithelial cells generated Ca2+ and PKC signals and, consequently, increased exocytosis and mucin secretion. In the project, I found that Ca2+ influx through store-operated Ca2+ channels (SOCs) is a critical component for PAR-2 signal­ing. Therefore, I also characterized the biophysical properties of epithelial SOCs and their modulation by protein kinases (Kim et al., 2008; Kim et al., 2013) accordingly. In parallel, one of the exocytosis mechanisms in melatonin-secreting pinealocytes was investigated. Contrary to our initial search for glutamate receptors, we unexpectedly found that glutamate transporters are expressed in the cells. We found that glutamate transporters can depolarize the membrane, bringing Ca2+ into the cytoplasm, and thus evoking glutamate exocytosis (‘glutamate-induced glutamate exocytosis’; Kim et al., 2008).

·         Kim, M.H., Seo, J.B. Burnette, L., Hille, B., Koh, D.S. (2013). Characterization of store- operated Ca2+ channels in pancreatic duct epithelia. Cell Calcium 54, 266-275.

·         Kim, M.H., Uehara, S., Muroyama, A., Hille, B., Moriyama, Y., Koh, D.S. (2008). Glutamate transporter-mediated glutamate secretion in the mammalian pineal gland. J. Neurosci. 28, 10852- 10863.

·         Kim, M.H., Choi, B.H., Jung, S.R., Sernka, T.J., Kim, S., Kim, K.T., Hille, B., Nguyen, T.D., Koh, D.S. (2008). Protease-activated receptor-2 increases exocytosis via multiple signal transduction pathways in pancreatic duct epithelial cells. J. Biol. Chem. 283, 18711-18720.

·         Cho, J.H., Chen, L., Kim, M.H., Chow, R.H., Hille, B., Koh, D.S. (2010). Characteristics and functions of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate receptors expressed in mouse pancreatic α-cells. Endocrinology 151, 1541-1550.

·         Jung, S.R., Kim, M.H., Hille, B., Koh, D.S. (2009). Control of granule mobility and exocytosis by Ca2+-dependent formation of F-actin in pancreatic duct epithelial cells. Traffic 10, 392-410.

·         Kim, H.S., Yumkham, S., Lee, H.Y., Cho, J.H., Kim, M.H., Koh, D.S., Ryu, S.H., Suh, P.G. (2005). C-terminal part of AgRP stimulates insulin secretion through calcium release in pancreatic beta Rin5mf cells. Neuropeptides 39, 385-393.

·         Kim, J.H., Nam, J.H., Kim, M.H., Koh, D.S., Choi, S.J., Kim, S.J., Lee, J.E., Min, K.M., Uhm, D.Y., Kim, S.J. (2004). Purinergic receptors coupled to intracellular Ca2+ signals and exocytosis in rat prostate neuroendocrine cells. J. Biol. Chem. 279, 27345-27356.

·         Jung, S.R., Kim, M.H., Hille, B., Nguyen, T.D., Koh, D.S. (2004). Regulation of exocytosis by purinergic receptors in pancreatic duct epithelial cells. Am. J. Physiol., Cell Physiol. 286, C573- 579.

·         Lee, I.S., Hur, E.M., Suh, B.C., Kim, M.H., Koh, D.S., Rhee, I.J., Ha, H., Kim, K.T. (2003). Protein kinase A-and C-induced insulin release from Ca2+-insensitive pools. Cell. Signal. 15, 529-537.