Abstracts

RATIONALE: Cortical dysplasia is associated with intractable epilepsy but little is known about the underlying mechanisms. Synaptic strength and plasticity are important determinants of cortical function in normal and pathological states. Excitatory responses in normal cortical neurons show synaptic depression at age 2 wk that converts to facilitation by age 4 wk. We used an animal model that produces cortical dysplasia to determine if properties of synaptic plasticity in the developing cortex were altered in this condition.
METHODS: Pregnant rats were exposed to 225 cGy of external [gamma]-irradiation on E17. Offspring were born normally and tested at 13-16 days and 28-42 days of age. Age matched control animals were also used. 400 [mu]m-thick coronal hemispheric slices were prepared at the level of the anterior commissure and placed in a submersion-type recording chamber. Pyramidal cells from normal and dysplastic cortex were identified using IR-DIC microscopy and whole cell patch clamp recordings were obtained in voltage clamp configuration. Series of five stimulus-evoked, monosynaptic EPSCs were recorded from pyramidal cells in control and dysplastic cortex at frequencies of 20 and 50 Hz. Responses were quantified as percent change with respect to the initial EPSC amplitude and compared between the two experimental groups.
RESULTS: Control neocortical pyramidal cells showed synaptic depression at age 2 wk (n = 4) in response to both 20 and 50 Hz stimulation. By age 4 wk (n = 12) this response had changed to robust facilitation. Pyramidal cells from dysplastic cortex showed synaptic depression in response to 20 and 50 Hz stimulation at age 2 wk (n = 6). At age 4-6 wk (n = 9), pyramidal cells from dysplastic cortex continued to show synaptic depression and this was signficantly different than the control cells at this age (p [lt] 0.001).
CONCLUSIONS: As previously described (Reyes and Sakmann, 1999), excitatory responses in normal cortical pyramidal cells switch from synaptic depression to facilitation between ages 2 and 4 wk. Pyramidal cells in dysplastic cortex show the immature response (depression) at both ages. These data demonstrate a delay, or possibly an arrest, of maturation of one type of synaptic plasticity in dysplastic cortex. Although the underlying mechanisms for this persistent synaptic depression are under investigation, an increased initial release probability in excitatory pre-synaptic terminals in dysplastic cortex provides one plausible explanation.
Support: NINDS (NS35651)