Abstracts

Rationale: GABAergic interneurons play a critical role in normal function of the CNS. Dysfunction of the interneurons has been indicated in neuronal and mental disorders, such as epilepsy and schizophrenia. There are two major subtypes of cortical interneurons, which express either pavalbumin(PV) or somatostatin(SS). They have distinct intrinsic and synaptic properties, indicating they may play different roles in normal and abnormal function of the CNS. In the present study, we have examined the developmental changes in the intrinsic and synaptic properties of two subtypes of interneurons. Methods: Two strains of transgenic mice, which express eGFP in PV and SS positive interneurons respectively, were purchased from the Jackson lab. Coronal slices of somatosensory cortex were obtained from mice at different ages (P10, P16 and P25). Whole-cell recordings were performed on neurons with GFP in layer V identified under fluorescent microscopy. The firing properties were examined in a current-clamp configuration by injecting depolarizing currents (300 pA, 300ms) at a membrane potential of -60mV. Synaptic properties were evaluated by recording spontaneous and miniature postsynaptic currents (sEPSCs and mEPSCs) under a voltage clamp mode at a holding potential of -60mV. Short-term plasticity was examined by using paired-pulse stimulation. Results: Action potential (AP) frequency with depolarizing current (300 pA, 300 ms) increased during the first postnatal month in both subtypes of interneurons (P10: 77Hz, P 16: 104 Hz and P25: 140Hz for PV neurons; 48Hz, 58Hz and 72Hz for SS neurons). However, AP frequency was significantly higher in PV neurons compared to SS neurons in all age groups (p< 0.05). TEA (1mM), which blocked Kv3 channels, significantly reduced the firing frequency in SS neurons (69Hz without TEA, 54 Hz with TEA, n = 6, p<0.05), but not in PV neurons (136 Hz without TEA, 133 Hz with TEA, n = 5, p>0.05). The frequencies of sEPSCs and mEPSCs of both PV and SS neurons increased during the development. The amplitude, however, did not change significantly. The frequency of mEPSCs was not significantly different from sEPSCs in PV neurons but it was much lower than sEPSCs in SS neurons. Paired-pulse stimulation always induced depression in PV neurons and facilitation in SS neurons and there were no significant changes during the development for either subtype (p>0.05). Conclusions: The intrinsic and synaptic properties are continuously modified during the initial postnatal period for both PV and SS neurons. However, the mechanisms underlying these modifications may be different between different subtypes. Our future work will explore the roles of these developmental modifications in neuronal abnormalities in the CNS.