学术报告 | 小胶质细胞和星形胶质细胞对皮层环路的主动监测与重塑

Actively Survey and Remodeling of Cortical Circuits by Microglia and Astrocyte

• 主持人：

  Akihiro Yamanaka博士

• 报告时间：

  2024年11月15日

  10:00-11:00

• 报告地点：

  北京脑科学与类脑研究所
  

  二期X102报告厅

• 报告语言：

  英语

Actively Survey and Remodeling of Cortical Circuits by Microglia and Astrocyte

Two topics on the interaction between cortical Synapses and glia will be introduced.

Microglia constantly move their processes and contact with neuronal elements in an in vivo brain. 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. In damaged brain, microglia extended their processes toward neuronal elements damaged and rescued neurons by suppression of the neuronal excitotoxicity. On the other hand, in immature brain, microglia contact onto neuronal dendrites induced the generation of synapses and cortical circuits (Miyamoto et al. Nat Comm 2016). Thus, microglia adapt their modulatory action on neurons in various brain environments. In addition, spatiotemporal Ca²⁺ dynamics of microglia in awake mice will be introduced.

Second, the pathogenesis of chronic pain hypersensitivity after peripheral nerve injury can be conceptualized as a two-step process with distinct developmental and maintenance phases. During the developmental phase, astrocyte become activated and release thrombospondin 1 which promotes neuronal circuit rewiring. In the primary somatosensory cortex (S1) of mice, this contributes to establishing of putative pathological circuits (Kim et al. J Clin Exp 2016). In this process, spines existing before peripheral injury are preferentially replaced with those newly generated after injury. During the maintenance phase, astrocyte activity and neuronal plasticity become reduced – a potential mechanism underlying the long-term maintenance of allodynia. This idea prompts us to attempt astrocyte re-activation and re-introduce increased plasticity in S1 circuits during the maintenance phase to dismantle pathological circuits. Indeed, during the maintenance phase in chronic pain model mice, transient astrocyte re-activation, combined with transient decrease in the hypersensitivity, produces lasting long-term relief from allodynia (Takeda et al. Nat Comm 2022). During the application period of this combination treatment, synaptic spines generated during the developmental phase are preferentially eliminated. This likely corresponds to pain-related synapse elimination resulting in relief from allodynia. With the aim of clinical application, we also trial reported methods for activating astrocytes via transcranial direct stimulation (tDCS), combining this with local anesthetics. Both procedures are individually widely used to temporarily relieve chronic pain, but when combined here provide lasting relief from allodynia extending beyond the treatment period. Thus, this could be a new strategy for treating chronic pain in the clinic.