Microglia regulate neuronal network formation and synaptogenesis

Abstract

Microglia are the resident immune cells of the central nervous system (CNS) and play an essential role under physiologic and pathologic conditions. Next to their well‐established role in the progression in neurodegenerative diseases such as Alzheimer’s disease (AD) and Parkinson’s disease (PD), recent reports underline the involvement of microglia during postnatal CNS maturation. The main objective of the present study was to examine the influence of microglia on neuronal network formation and synaptogenesis in cortical/midbrain neuron cultures.Primary mouse E14 cortical/midbrain neuron cultures were used to determine the development of functional synapses in the presence and absence of microglia. Microglia depletion was performed using the Csf1r inhibitor BLZ945. Neuronal network formation and maturation of synapses were analyzed using the Microelectrode Array Technology (MEA) and immunocytochemistry labeling of synaptic markers such as Synapsin and PSD95.Electrophysiology using MEAs indicated that microglia regulate the abundance of functional synapses during a time of 28 days in vivo (DIV). Using a Csf1r inhibitor, we were able to show that the efficient depletion of microglia abrogated the inhibitory effects on synaptogenesis.Taken together, our data demonstrate that microglia are effective regulators of neuronal network formation and synaptic connectivity further broadening the portfolio of versatile functions of these resident immune cells of the central nervous system.