Semilunar Granule Cells: Glutamatergic Neurons in the Rat Dentate Gyrus with Axon Collaterals in the Inner Molecular Layer

Abstract

Synaptic reorganization of the dentate gyrus inner molecular layer (IML) is a pathophysiological process that may facilitate seizures in patients with temporal-lobe epilepsy. Two subtypes of IML neurons were originally described by Ramón y Cajal (1995), but have not been thoroughly studied. We used two-photon imaging, infrared-differential interference contrast microscopy and patch clamp recordings from rat hippocampal slices to define the intrinsic physiology and synaptic targets of spiny, granule-like neurons in the IML, termed semilunar granule cells (SGCs). These neurons resembled dentate granule cells but had axon collaterals in the molecular layer, significantly larger dendritic arborization in the molecular layer, and a more triangular cell body than granule cells. Unlike granule cells, SGCs fired throughout long-duration depolarizing steps and had ramp-like depolarizations during interspike periods. Paired recordings demonstrated that SGCs are glutamatergic and monosynaptically excite both hilar interneurons and mossy cells. Semilunar granule cells appear to represent a distinct excitatory neuron population in the dentate gyrus that may be an important target for mossy fiber sprouting in patients and rodent models of temporal lobe epilepsy.

Decrease in Tonic Inhibition Contributes to Increase in Dentate Semilunar Granule Cell Excitability after Brain Injury

“…Similar to observations in naive rats (Williams et al, 2007), dendrites of SGCs from sham-injured rats had a wider span compared with the relatively compact dendritic spread of granule cells ( Fig. 2 A, B; maximum dendritic spread in m, granule cell: 289.0 Ϯ 24.0, n ϭ 8; SGC: 509.6 Ϯ 40.1, n ϭ 11, p Ͻ 0.05, t test).…”

“…In experiments where spontaneous and miniature IPSCs (mIPSCs) were recorded as outward currents from a holding potential of 0 mV, the internal solution consisted of the following (in mM): 125 Csmethanesulfonate, 5 NaCl, 10 HEPES, 0.2 EGTA, 2 Mg-ATP, 0.2 Na-GTP, and 5 QX-314 with biocytin (0.2%). Among neurons recorded in the IML, only cells showing the widespread dendritic morphology and axon projecting to the hilus (Williams et al, 2007) were analyzed and included in the study. Recordings were discontinued if series resistance increased by Ͼ20%.…”

“…Although increases in excitability of granule cells or mossy cells are potential direct mechanisms to account for post-traumatic increases in dentate field excitability, little postinjury change in firing has been found in these two dentate glutamatergic neurons (Santhakumar et al, 2000;Howard et al, 2007). We examined whether the excitability of SGCs, a population of neurons originally described by Ramó n y Cajal (1995) and recently characterized as glutamatergic dentate projection neurons (Williams et al, 2007), is altered after brain injury.…”

“…These have recently been identified as the prime orchestrators of persistent firing in hilar neurons (Larimer and Strowbridge, 2010). Although SGCs, like granule cells, project to CA3, they are unique in the presence of molecular layer axon collaterals (Williams et al, 2007), which could contribute to synaptic excitation of neighboring granule cells. Physiologically, afferent stimulation evokes persistent firing in SGCs, which underlie prolonged synaptic barrages in hilar neurons (Williams et al, 2007).…”

“…Although SGCs, like granule cells, project to CA3, they are unique in the presence of molecular layer axon collaterals (Williams et al, 2007), which could contribute to synaptic excitation of neighboring granule cells. Physiologically, afferent stimulation evokes persistent firing in SGCs, which underlie prolonged synaptic barrages in hilar neurons (Williams et al, 2007). Thus, SGCs are in a pivotal position to regulate dentate feedback circuits and have been proposed to contribute to the integrity of the physiological "dentate gate" (Heinemann et al, 1992) that regulates granule cell throughput (Larimer and Strowbridge, 2010).…”