Article Figures & Data
Figures
- Fig. 1.
Horizontal section of the hippocampus and DG in a normal rat stained by the Timm method demonstrates the normal terminal field of the mossy fiber axons arising from granule cells in the DG. Dense areas of dark staining areas in the DG and CA3 fields are locations of synapses of mossy fiber axons, which stain darkly because of their high content of Zn. The area outlined by thebox is the standard location in the DG that was evaluated by scoring methods for Timm histochemistry. H, Hilus; DG, dentate gyrus. Scale bar, 1000 μm.
- Fig. 2.
Examples of continuous recordings from a depth electrode in the perforant path of rats that received injections of either saline (A) saline or MK801 (B) 30 min before stimulation of the perforant path with a 1 sec train of 62 Hz, 1 msec biphasic constant current pulses (arrowhead). A, In a saline-injected rat, a perforant path stimulus of 500 μA evoked an AD that began with a brief run of high-frequency spike discharges that was immediately followed by repetitive irregular spike and spike-wave discharges that gradually decreased in frequency, which were followed by lower-amplitude featureless activity. The arrowindicates the end of the AD, which had a duration of 43 sec.B, In a rat treated with MK801 30 min before perforant path stimulation, a 1400 μA stimulus train evoked an AD that also began with brief high-frequency discharges that evolved into repetitive spike and irregular spike-wave discharges. The arrow at the onset of low-amplitude featureless activity indicates the end of the AD, which had a duration of 64 sec. Calibration bars are for bothA and B. Rats pretreated with MK801 had a higher initial AD threshold and experienced ADs of longer duration than saline-injected controls (see text and Table 2 for details).
- Fig. 3.
Higher-magnification views of horizontal Timm-stained sections in the standard location in the DG described in Figure 1. A, Higher magnification of the boxed area in Figure 1 demonstrates the appearance of the supragranular area of the DG from a normal rat, which is not innervated by mossy fiber axons and has few or no dark staining granules (open arrows). B, Higher magnification of the same region in a kindled rat that received once-daily stimulation that evoked 14 afterdischarges and 1 class V secondary generalized tonic–clonic seizure. The supragranular region contains numerous dark Timm granules corresponding to synapses of mossy fiber axons, which form a laminar band (filled arrows).C, Higher magnification from the same region in a rat that received MK801 before each stimulation until 17 afterdischarges were evoked. Timm granules are present in the supragranular layer (filled arrows) but are not as prominent as in the untreated rat in B. D, Higher magnification from the same region in a rat that received MK801 before each stimulation beginning after the 10th afterdischarge and continuing until 1 class V seizure was evoked. The supragranular region contains numerous dark Timm granules that form a laminar band (filled arrows). Untreated rats that experienced 1 class V seizure had comparable mossy fiber synaptic reorganization, as assessed by Timm scores (see Table 2). H, Hilus. Scale bar (shown in A): 100 μm.
- Fig. 4.
A, Higher magnification of the DG in a kindled rat that received once-daily stimulation that evoked 25 afterdischarges and 10 class V secondary generalized tonic–clonic seizures. The supragranular region contains numerous dark Timm granules corresponding to synapses of mossy fiber axons, which form a laminar band (filled arrows).B, Higher magnification from the same region in a rat that received MK801 before each stimulation after the first class V seizure and continuing until 10 class V seizures were evoked. This rat required 34 afterdischarges to evoke 10 class V seizures. The supragranular region also contains a laminar band of Timm granules (filled arrows). H, Hilus. Scale bar (shown in A): 100 μm.
- Fig. 5.
Summary of the effects of MK801 on the kindling rate and mossy fiber synaptic reorganization for groups of control rats and rats treated with MK801. The kindling rate was expressed as the mean number of afterdischarges, and mossy fiber synaptic reorganization was assessed by mean Timm scores. The error bars indicate the SEM for each group; *, versus Timm score for CONTROL 1 CL V, p = 0.032; **, versus kindling rate forCONTROL 1 CL V, p = 0.012; ***, versus kindling rate for CONTROL 10 Cl V, p = 0.024.
Tables
1st AD1_150 10th AD 11th AD 17th AD 1st class V 2nd class V 10th class V Controls 561 ± 42 495 ± 39 491 ± 40 467 ± 79 467 ± 47 − − 1 class V Controls 562 ± 73 490 ± 60 484 ± 61 437 ± 61 435 ± 55 417 ± 57 314 ± 52 10 class V MK801 1007 ± 1331_151 900 ± 102 885 ± 106 785 ± 100 − − − 0–17 ADs MK801 572 ± 49 517 ± 44 505 ± 49 439 ± 42 364 ± 35 − − 10 ADs–1 class V MK801 594 ± 53 575 ± 67 566 ± 66 455 ± 43 471 ± 49 453 ± 44 282 ± 33 1–10 class V Experimental group AD2_150 Cumulative AD duration (sec)2_150 Timm score2_150 Normal control (n = 7) − − 0.8 ± 0.13 Kindling 17.2 ± 1.8 624 ± 54 3.44 ± 0.29 1 Cl V (n = 9) MK801 17 840 ± 582_a 2.43 ± 0.322_b 0–17 ADs (n = 7) MK801 24.2 ± 1.7 1166 ± 1102_c 3.39 ± 0.22 10 AD–1 Cl V (n = 9) Kindling 29.3 ± 1.6 1451 ± 83 3.54 ± 0.3 10 Cl V (n = 8) MK801 35.7 ± 1.9 2066 ± 482_d 3.29 ± 0.27 1–10 Cl V (n = 9)
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