Abstracts

After fluid percussion injury (FPI), a large number of mossy cells in the dentate gyrus die. However, the loss of mossy cells does not lead directly to hyperexcitability of dentate granule cells (Ratzliff et al., J Neurosci. 2004 24:2259-69). The [ldquo]irritable mossy cell hypothesis[rdquo] proposes that the surviving mossy cells themselves are either hyperexcitable or spread hyperexcitability, thereby contributing to the hyperexcitability of dentate granule cells (Santhakumar et al, J Physiol. 2000 524:117-34; Ratzliff et al., Trends Neurosci. 2002 25:140-42). In this study, we tested this hypothesis by examining the intrinsic properties of surviving mossy cells. Whole-cell recordings were made from prelabeled mossy cells (Ratzliff et al., 2004) in 350 [mu]m horizontal hippocampal slices at 32[deg]C. Slices were obtained from P20-P23 rats 5-8 days after fluid percussion injury or sham injury. The intracellular solution contained (in mM): 140 K Gluconate, 2 MgCl[sub]2[/sub], and 10 mM N-2-hydroxyethylpiperazine-N-2-ethanesulfonic acid (HEPES). The bath was perfused with ACSF containing 5 [mu]M NBQX and 10 [mu]M AP-5. Statistics were performed using Student[rsquo]s t-test, with significance set at p [lt]0.05. The resting membrane potential of mossy cells after FPI was significantly depolarized compared to controls (FPI: -63.12 +/- 0.84 mV, Control: -66.56 +/- 1.35 mV). Intrinsic properties of mossy cells were measured in current clamp configuration using 500 ms using current steps from -320 to +440 pA, incrementing by 40 pA, from a holding potential of -60mV. The amplitude of the depolarizing sag in response to hyperpolarizing current pulses was significantly increased at current pulses between -40 and -280 pA (at -200 pA steps, FPI: 8.1 +/- 1.1 mV, CON: 5.6 +/-0.7 mV) . In addition, the afterdepolarization seen after the termination of hyperpolarization was significantly increased at negative current steps between -40 and -320 pA (at -200 pA steps, FPI: 4.9 +/- 0.7 mV, CON: 2.5 +/- 0.7 mV). Mossy cells which survive head injury exhibit long-lasting changes in their intrinsic properties following the insult. The changes seen, an increased resting membrane potential, increased depolarizing sag, and increased afterdepolarization, are all consistent with an increased expression of I[sub]h[/sub]. Increase in I[sub]h[/sub] can modulate increased neuronal excitability in complex ways. (Chen et al., Trends Pharmacol Sci. 2002 23:552-7). The changes seen here could be expected to have large downstream effects since mossy cells are uniquely positioned to spread excitability through the hippocampus due to their long-ranging associational and commissural projections. (Supported by NIH (NS35915) to I.S.)