MOSSY CELL DELETION DOES NOT CAUSE HYPEREXCITABILITY IN THE DENTATE GYRUS: IMPLICATIONS FOR EPILEPSY
Abstract number :
1.081
Submission category :
Year :
2003
Submission ID :
3904
Source :
www.aesnet.org
Presentation date :
12/6/2003 12:00:00 AM
Published date :
Dec 1, 2003, 06:00 AM
Authors :
Anna d.H. Ratzliff, Allyson L. Howard, Ivan Soltesz Anatomy & Neurobiology, University of California, Irvine, CA
Loss of mossy cells and interneurons from the hilus of the dentate gyrus is a major histological hallmark of human temporal lobe epilepsy. Mossy cells can influence the activity of granule cells both directly through excitatory synapses and indirectly by exciting interneurons. However, the net effect of mossy cell activity in normal circuits and the consequences of mossy cell loss in epileptogenesis remain controversial.
Mossy cells were identified and differentiated from hilar interneurons in living slices using a fluorescent retrograde tracer injected in vivo into the contralateral dentate gyrus. Acute ablation of either pre-labeled mossy cells or hilar-granule cell border interneurons was performed by visually directed, controlled, rapid single cell aspiration using an enlarged patch pipette. Perforant path evoked granule cell field responses were recorded before and after ablation.
Ablation of mossy cells caused a significant decrease in granule cell layer fEPSP peak amplitude (84.6[plusmn]1.1% of pre-ablation) and population spike amplitudes (60.2[plusmn]5.7 % of pre-ablation). In contrast, control ablation of interneurons caused a significant increase in fEPSP amplitude (111.8[plusmn]1.2% of pre-ablation). To assess the effect of mossy cell activity along the septo-temporal axis of the hippocampus, mossy cells were ablated in slices cut along the longitudinal axis. Even at a distance greater than 2mm away from the site of ablation, a significant decrease in the granule cell fEPSP (87.3[plusmn]6.1% of pre-ablation) was recorded.
Using novel techniques to study mossy cells in the normal dentate circuit, we demonstrate that the acute ablation of mossy cells in both the horizontal and axial slice preparations causes hypoexcitability in granule cells. These data demonstrate that the net effect of mossy cell activity is to excite granule cells and is in agreement with the [ldquo]irritable mossy cell[rdquo] hypothesis (Santhakumar et al, J Physiol, 2000; Ratzliff et al., TINS, 2002) of epileptogenesis.
[Supported by: The NIH (NS35915) to IS and UCI-MSTP to AR and AH.]