1 Reduced Chemical and Electrical Connections of Fast - Spiking Interneurons 2 in Experimental Cortical Dysplasia 3 4 5

23 Aberrant neural connections are regarded as a principal factor contributing to epileptogenesis. This 24 study examined chemical and electrical connections between fast-spiking (FS), parvalbumin (PV) 25 immunoreactive (Ir, FS-PV) interneurons and regular spiking (RS) neurons (pyramidal neurons or 26 spiny stellate neurons) in a rat model of prenatal irradiation-induced cortical dysplasia. Presynaptic 27 action potentials were evoked by current injection and the elicited unitary inhibitory or excitatory 28 postsynaptic potentials (uIPSPs or uEPSPs) were recorded in the postsynaptic cell. In dysplastic 29 cortex, connection rates between presynaptic FS-PV interneurons and postsynaptic RS neurons and 30 FS-PV interneurons, and uIPSP amplitudes were significantly smaller than controls. But both failure 31 rates and coefficient of variation of uIPSP amplitudes were larger than controls. In contrast, connection 32 rates from RS neurons to FS-PV interneurons and uEPSPs amplitude were similar in the two groups. 33 Assessment of the paired pulse ratio showed a significant decrease in synaptic release probability at 34 FS-PV interneuronal terminals and the density of terminal boutons on axons of biocytin-filled FS-PV 35 interneurons was also decreased, suggesting presynaptic dysfunction in chemical synapses formed by 36 FS-PV interneurons. Electrical connections were observed between FS-PV interneurons, and the 37 connection rates and coupling coefficients were smaller in dysplastic cortex than controls. In dysplastic 38 cortex, we found a reduced synaptic efficiency for uIPSPs originating from FS-PV interneurons 39 regardless of the type of target cell and impaired electrical connections between FS-PV interneurons. 40 This expands our understanding of the fundamental impairment of inhibition in this model and may 41 have relevance for certain types of human cortical dysplasia. 42 43