Abstracts

Rationale: Aberrant neural connections are regarded as a principal contributing pathophysiological mechanism in epileptogenesis. In this study, we examined the synaptic interconnections between pairs of inhibitory and excitatory cortical neurons in an animal model of cortical dysplasia (CD).Methods: Pregnant rats received 225 cGy of external -irradiation or sham-irradiation on E17. Four- to five-week-old male offspring were subjected to experiments. Coronal slices (400 microns thick) were obtained from the somatosensory cortex. We chose two adjacent somata for dual somatic whole cell recordings. We tested the synaptic interconnections of parvalbumin immunoreactive fast-spiking (FS) interneurons and regular spiking (RS) pyramidal neurons. Presynaptic action potentials were evoked by brief, depolarizing current pulses from one cell and the elicited unitary inhibitory or excitatory postsynaptic potential (uIPSP or uEPSP) was recorded in the postsynaptic cell.Results: The connection rates from FS interneurons to RS pyramidal neurons were significantly lower in irradiated rats than in controls (Table 1; P<0.05). The amplitude of uIPSPs for connected interneuron-to-pyramid pairs in irradiated rats was significantly smaller compared to controls (Table 1; P<0.01). However, the connection rates and the amplitude of uEPSPs from RS neuron to FS interneuron pairs were similar between control and irradiated rats (both P>0.05). Of the 81 pairs of FS-RS recordings in control and 52 pairs in irradiated rats, 9 pairs in control and 2 pairs in irradiated rats had reciprocal connections. We also recorded 41 pairs of FS interneurons in control and 25 pairs in irradiated rats. The connection rates were lower in irradiated rats than in controls (Table 1; P<0.01). The amplitude of uIPSPs from FS-FS pairs was significantly smaller in irradiated rats than in controls. Both the failure rates and the coefficient of variation (CV) of PSP amplitude from the connections of FS interneurons to RS neurons and between FS interneurons were significantly increased in dysplastic cortex (Table 1; P<0.01); however, they were not significantly changed in the connections from RS neurons to FS interneurons in dysplastic cortex. Conclusions: FS interneurons of irradiated rats have more sparse and weaker connections to their neighboring RS pyramidal neurons compared to controls. The excitatory connections from pyramidal neurons to FS interneurons are similarly distributed and equally strong in the two groups. The probability of inhibitory neurotransmitter release by activation of presynaptic terminals from FS interneurons is decreased in dysplastic cortex while the release probability of excitatory terminals from pyramidal neurons (onto FS interneurons) may not be changed in dysplastic cortex. These findings provide additional insight into the impaired inhibition that is seen in this model of CD and may have relevance for certain types of human CD.