Title:
Long term-remodeling of neuronal circuits in vivo: neuron-glia interaction.

 

Junichi Nabekura, MD, PhD
National Institute for Physiological Sciences, Okazaki, Japan.

 

Abstract:
Two topics regarding glia-neuron interaction will be prepared in this seminar, interactions of microglia and astrocyte with neurons in an in vivo brain
Microglia are the sole immune cell in the brain and survey the micro-environments with dynamic motility of their processes (Wake et al. 2009, Haruwaka et al 2020). As for functional significance of microglia contact to neuronal elements, their contact on synapses facilitated synaptic transmission and synchronous activity of neurons local neuronal circuits (Akiyoshi, et al. 2018). In damaged brain, microglia extended their processes toward neuronal elements damaged and rescued neurons by suppression of the neuronal excitotoxicity (Kato et al. 2016). On the other hand, in immature brain, microglia contact onto neuronal dendrites induced the generation of synapses and cortical circuits (Miyamoto et al. 2016). Thus, microglia adapt their modulatory action on neurons in various brain environments.
Second, in chronic pain model, the temporal activation of astrocyte during the developmental phase after peripheral nerve injury released thrombospondin 1 leading the generation of pain-related synapses in the somatosensory cortex (S1). Thereafter, reduced activity of astrocyte maintains the pathological circuits, resulting in long lasting allodynia (Kim et al. 2016). To relieve allodynia in the maintenance phase, we attempt the re-activation of S1 astrocyte in combination with reduced activity of peripheral nerve. This combination predominantly eliminates the synapses generated in the developmental phase of allodynia (pain-related synapses) and successfully relieved the hypersensitivity. We attempt to modify this combination for clinical trial.

 

 

Publications:

1, Haruwaka K, Ikegami A, Tachibana Y, Ohno N, Hiroyuki, Konishi H, Hashimoto A, Matsumoto M, Kato D, Ono R, Kiyama H, Moorhouse AJ, Nabekura J, Wake H. (2019) Dual Microglia Effects on Blood Brain Barrier Permeability Induced by Systemic Inflammation. Nature Communications 10(1):5816. doi: 10.1038/s41467-019-13812-z.

2, Akiyoshi R, Wake H, Kato D, Horiuchi H, Ono R, Ikegami A, Haruwaka K,
Omori T, Tachibana Y, Moorhouse AJ, Nabekura J (2018)　Microglia enhance synapse activity to promote local network synchronization.eNeuro 5(5):eNEURO.0088-18. doi: 10.1523/ENEURO.0088-18.

3, Kato G, Inada H, Wake H, Akiyoshi R, Miyamoto A, Eto K, Ishikawa T, Moorhouse AJ, Strassman AM, Nabekura J. Microglial contact prevents excess depolarization and rescues neurons from excitotoxicity (2016). eNeuro 3(3):eNEURO.0004-16. doi: 10.1523/ENEURO.0004-16.

4, Miyamoto A, et al. (2016). Microglia contact induced synapse formation in developing somatosensory cortex. Nature Communications 7:12540, 2016. doi: 10.1038/ncomms12540

5, Kim SK, et al. (2016) Cortical astrocytes rewire somatosensory cortical circuits for peripheral neuropathic pain. Journal of Clinical Investigation 126(5):1983-97. doi: 10.1172/JCI82859.