Abstracts

Pyramidal neurons in hippocampus have non-uniform distributions of ion channels. One example is the low somatic yet high dendritic density of hyperpolarization activated cation channels (h-channels; [italic]I[/italic][sub]h[/sub]). With the modulation of h-channels recently implicated in epilepsy (Poolos et al, [italic]Nat Neurosci.[/italic], 5: 767, 2002), the localization of [italic]I[/italic][sub]h[/sub] within the hippocampus may be important to furthering our understanding of epileptogenesis. We investigated a distinct subset of hippocampal principal cells with pyramidal morphology located in stratum radiatum to determine if these neurons have similar non-uniform somatodendritic ion channel distributions. Experiments were performed on hippocampal brain slices obtained from male Sprague-Dawley rats using standard techniques. We studied [italic]I[/italic][sub]h[/sub] with cell-attached voltage-clamp recordings in the soma and dendrites of neurons visualized through IR-DIC microscopy. Cells were filled with biocytin, stained with antibodies against GAD 65/67, and viewed with fluorescent confocal microscopy. The morphology, GAD immunoreactivity, and [italic]I[/italic][sub]h[/sub] kinetics for pyramidal-like principal neurons (PLPs) in stratum radiatum were compared to CA1 pyramidal neurons. Under IR-DIC, PLPs were located about 25 [mu]m into proximal stratum radiatum of CA1. These neurons had a pyramidal soma and displayed one prominent apical dendrite extending toward stratum lacunosum moleculare that bifurcated at 110-150 [mu]m from the soma, and had a dendritic morphology similar to CA1 pyramidal neurons. Axons emanated from the basal soma and projected toward stratum oriens/alveus, where they turned to run parallel with the alveus. PLPs were negative for GAD immunoreactivity. Cell-attached patch recordings revealed a high [italic]I[/italic][sub]h[/sub] density in the somas of PLPs. The maximal current was 33 [plusmn] 6 pA (mean [plusmn] SEM; [italic]n[/italic] = 9), a 3-6 fold higher density than reported values for CA1 pyramidal somas (Magee JC, [italic]J Neurosci.[/italic], 19: 7613, 1998). The current densities of the PLP somata were comparable to pyramidal dendrites (39 [plusmn] 15 pA; [italic]n[/italic] = 7). In the proximal PLP dendrites, current density declined (18 [plusmn] 5 pA; [italic]n[/italic] = 5), contrary to the increase observed in pyramidal dendrites. The half-maximum activation voltage and the slow and fast activation time constants were similar between pyramidal neurons and PLPs, suggesting a similar composition of h-channels in both cells. We have found that the somatodendritic distribution of h-channels can vary between two types of hippocampal principal neurons with pyramidal morphology. These findings indicate differing excitability of PLPs compared to pyramidal neurons, while their location within the hippocampus suggests they may be related to the radiatum giant cell (Gulyas et al, [italic]Eur J Neurosci.[/italic], 10: 3813, 1998). (Supported by NINDS and the Epilepsy Foundation.)