Abstract
The perirhinal cortex (PRC) is a supra-modal cortical area that collects and integrates information originating from uni- and multi-modal neocortical regions and directed to the hippocampus. The mechanisms that underlie the specific excitable properties of the different PRC neuronal types are still largely unknown, and their elucidation may be important in understanding the integrative functions of PRC. In this study we investigated the expression and properties of resurgent Na(+) current (I(NaR)) in pyramidal neurones of rat PRC area 35 (layer II). Patch-clamp experiments in acute PRC slices were first carried out. A measurable I(NaR) was expressed by a large majority of neurones (31 out of 35 cells). I(NaR) appeared as an inward, slowly decaying current elicited upon step repolarization after depolarizations sufficient to induce nearly complete inactivation of the transient Na(+) current (I(NaT)). I(NaR) had a peak amplitude of approximately 2.5% that of I(NaT), and showed the typical biophysical properties also observed in other neuronal types (i.e. cerebellar Purkinje and granule cells), including a bell-shaped current-voltage relationship with a peak at approximately -40 mV, and a characteristic acceleration of activation and decay speed at potentials negative to -45 mV. Current-clamp experiments were then carried out in which repetitive action-potential discharge at various frequencies was induced with depolarizing current injection. The voltage signals thus obtained were then used as command waveforms for voltage-clamp recordings. These experiments showed that a Na(+) current identifiable as I(NaR) activates in the early interspike phase even at relatively high firing frequencies (20 Hz), thereby contributing to the depolarizing drive and possibly enhancing repetitive discharge. In acutely dissociated area 35 layer II neurones, as well as in nucleated patches from the same neurones, I(NaR) was never observed, despite the presence of typical I(NaT)s. Since in both preparations neuronal processes are lost, we carried out experiments of focal tetrodotoxin (TTX) application in slices to verify whether the channels responsible for I(NaR) are located in compartment(s) different from the soma. We found that TTX preferentially inhibited I(NaR) when applied close to the site of axon emergence from soma, whereas application to the apical pole of the soma had a significantly smaller effect on I(NaR). Our results indicate that in area 35 pyramidal cells I(NaR) is largely generated in the axon initial segment, where it may participate in setting the coding properties of these neurones.