Enhanced synaptic connectivity and epilepsy in C1q knockout mice

• DOI: 10.1073/pnas.0913449107
• Publication Date: 2010-04-08T02:14:16Z
• Authors: Yunxiang Chu; Xiaoming Jin; Isabel Parada; Alexei Pesic; Beth Stevens; Ben Barres; David A. Prince
• Keywords: Photostimulation; Knockout mouse; Neuropil; Postsynaptic Current

Excessive CNS synapses are eliminated during development to establish mature patterns of neuronal connectivity. A complement cascade protein, C1q, is involved in this process. Mice deficient C1q fail refine retinogeniculate connections resulting excessive retinal innervation lateral geniculate neurons. We hypothesized that knockout (KO) mice would exhibit defects neocortical synapse elimination enhanced excitatory synaptic connectivity and epileptiform activity. recorded spontaneous evoked field potential activity slices obtained video-EEG recordings from implanted KO wild-type (WT) mice. also used laser scanning photostimulation caged glutamate whole cell map inhibitory Spontaneous potentials occurred at multiple sites KO, but not WT Laser mapping experiments showed the proportion uncaging which postsynaptic currents (EPSCs) could be ("hotspot ratio") increased significantly layer IV V, although EPSC amplitudes were unaltered. Density axonal boutons was V pyramidal neurons Implanted had frequent behavioral seizures consisting arrest associated with bihemispheric spikes slow wave lasting 5 30 s. Results indicate epileptogenesis related a genetically determined failure prune development.