INS Topical Seminar – Davide Ragozzino (Rome, Italy)
“Microglia shape presynaptic properties at developing glutamatergic synapses”
Deficient neuron-microglia signaling during brain development is associated with abnormal synaptic maturation. However, the precise impact of deficient microglia function on synaptic maturation and the mechanisms involved remain poorly defined.
Here we report that mice defective in neuron-to-microglia signaling via the fractalkine receptor (Cx3cr1 KO) show reduced microglial branching and altered motility and develop widespread deficits in glutamatergic neurotransmission. We characterized the functional properties of CA3-CA1 synapses in hippocampal slices from these mice and found that they display altered glutamatergic release probability, maintaining immature properties also at late developmental stages. In particular, CA1 synapses of Cx3cr1 KO show: (i) immature AMPA/NMDA ratio across developmental time displaying a normal NMDA component and a defective AMPA component of EPSC; (ii) defective functional connectivity, as demonstrated by reduced current amplitudes in the input/output curve; and (iii) greater facilitation in the paired pulse ratio (PPR), suggesting decreased release probability. In addition, minimal stimulation experiment revealed that excitatory synapses have normal potency, but an increased number of failures, confirming a deficit in presynaptic release. When the deficit in release probability was corrected by performing experiments in high Ca2+/Mg2+, excitatory synapses showed normal synaptic multiplicity and AMPA/NMDA ratio.
These results establish that neuron-microglia interactions profoundly influence the functional maturation of excitatory presynaptic synapse function.
For any question, feel free to contact:
Benjamin Morillon (firstname.lastname@example.org) or Adam Williamson (adam.WILLIAMSON@univ-amu.fr)