Abstracts

Rationale: Synaptic reorganization of the dentate gyrus inner molecular layer (IML) is a pathophysiological process that may facilitate seizures in patients with temporal lobe epilepsy. While most experimental work on this process has focused on granule cells, which are the source of the new excitatory synapses and the principal neuron of the dentate gyrus. Ramon y Cajal described two populations of neurons with cell bodies in the IML, which are potential targets for the new excitatory synapses. Little is known about the physiology and synaptic connections of IML cells, which include aspiny stellate cells and spiny triangulate or semilunar neurons. Methods: We used 2-photon imaging, IR-DIC microscopy and patch clamp recordings from rat hippocampal slices to define the intrinsic physiology, morphology, and synaptic targets of aspiny and spiny IML neurons. Results: Aspiny IML cells fired intermittently and resembled fast-spiking interneurons in other cortical areas. We found that these cells are GABAergic and monosynaptically inhibit granule cells. Spiny IML neurons resembled dentate granule cells but had axon collaterals in the molecular layer and dentate gyrus, significantly larger dendritic arborization than granule cells, and a more equilateral cell body than granule cells. Unlike granule cells, spiny IML neurons fired throughout long-duration (1-3 sec) depolarizing steps and had characteristic ramp-like depolarizations during inter-spike periods that resembled classical pacemaker potentials. The intrinsic properties of the spiny IML neurons (“pacemaker cells”) were significantly different from granule cells (i.e., lower input resistance, faster membrane time constant, larger fast and slow afterhyperpolarization). 2-Photon guided paired recordings demonstrated that pacemaker cells are glutamatergic and monosynaptically excite both hilar interneurons and mossy cells. Conclusions: Pacemaker neurons appear to represent an excitatory neuron population in the dentate gyrus that is distinct from granule cells and may be an important target for mossy fiber sprouting in patients and rodent models of temporal lobe epilepsy.