Olfactory epithelia exhibit progressive functional and morphological defects in CF mice.

Structural malformations of the cortex, arising as a result of genetic mutation or injury during development are associated with dyslexia, epilepsy, and other neurological deficits. We have used a rat model of a microgyral malformation to examine mechanisms of epileptogenesis. Our previous studies showed that the frequency of miniature excitatory postsynaptic currents (mEPSCs) recorded in neocortical layer V pyramidal neurons is increased in malformed cortex at a time when field potential epileptiform events can be evoked. Here we show that the increase occurs at an age before onset of cortical epileptiform activity and at a time when the frequency of mEPSCs in control layer V pyramidal neurons is stable. An increase in the frequency of spontaneous (s)EPSCs in layer V pyramidal neurons of malformed cortex occurs earlier than that for mEPSCs, suggesting that there may additionally be alterations in intrinsic properties that increase the excitability of the cortical afferents. Frequencies of EPSC bursts and late evoked activity were also increased in malformed cortex. These results suggest that a hyperinnervation of layer V pyramidal neurons by excitatory afferents occurs as an active process likely contributing to subsequent development of field epileptiform events.