1386 



HANDBOOK OF PHYSIOLOCl' 



NEUROFH'iSIOLOGV II 



evokina: the response did not reach the liippocampal 

 pyramids through the alveus. The possibihty of direct 

 axon collaterals, therefore, seems rather remote. The 

 usual point of recording corresponded roughly to 

 field hj. It is conceivable that axon collaterals, acti- 

 vated antidromically in, sa\-, area ha secondarily 

 acti\ate neurons in area h->. Since the latency of the 

 response was about 4 msec, it was considered that at 

 least two synapses might be inxolved. Since Lorente 

 de No (72, 73) had described afferent pathways 

 reaching the dentate gyrus from the fimbria, it seemed 

 not unreasonable that the primary relay might be in 

 the dentate gyrus, that the known pathway from the 

 granule cells to the pyramidal cells might be involved, 

 and that the secondary relay would then be in the 

 pvramidal cells, von Euler et al. (112) presented evi- 

 dence that the main region of depolarization, following 

 stimulation of the fornix, was around the soma and 

 basal part of the apical dendrite, but they believe that 

 repetitive stimulation produces successively greater 

 dendritic depolarization. Gloor (42) noted unit-like 

 activity in the dendritic layer following repetitive 

 stimulation. Buser & Rougeul (24) recorded intra- 

 cellularly in the hippocampal pyramids and noted 

 that the spike from the soma was followed by a pro- 

 longed hypcrpolarization which they attributed to the 

 dendrites. 



Seizure Discharges 



Jung (59) demonstrated that, following electro- 

 shock, the hippocampus showed the lowest threshold 

 of anv region in the cerebral hemisphere. Kaada (61), 

 by direct stimulation, found that the hippocampus 

 was second only in sensitivity to the pyriform- 

 amygdaloid region. Green & Morin (50, 80), 

 Green & .Shimamoto (51), .Segundo et al. (100) and 

 Creutzfeldt (29) determined that in curarized animals 

 the hippocampus had an exceedingly low threshold 

 and that it could be stimulated to paroxysmal electri- 

 cal discharge simply by the insertion of an electrode, 

 by lightly stroking the fimbria with a thread of cotton 

 soaked in saline or by pricking it lightly with a fine 

 needle. Andy & Akert (14) also found a very low 

 threshold ijut suggested that tubocurarine had in- 

 fluenced the level of excitability. Liberson & Cadilhac 

 (68-70) similarly found an exceedingly low threshold, 

 as low as any other part of the brain. The concensus 

 supports this observation. Personal experience indi- 

 cates that in the unanesthetized animal the threshold 

 is virtually as low as in the curarized animal. Seizure 

 discharges propagate from the hippocampus in all 



directions, but they are not dependent upon external 

 connections. Thus, seizure discharges can easily be 

 induced in the isolated hippocampus (45), as well as 

 after severing the hippocampal connections one by 

 one (51). Morin & Green (80) and Green & Shima- 

 moto (51) found that the seizure discharges were 

 propagated into the temporal lobe even though the 

 fornix was severed. At first sight, it would seem reason- 

 able that the generalization of the hippocampal dis- 

 charge might be through the fornix, mammillary body 

 and anterior thalamus, and thence, diffusely, to the 

 rest of the hemisphere. However, generalized dis- 

 charges in the hemisphere may be induced even after 

 the fornix has been completely removed by suction, 

 together with the thalamus, hypothalamus and reticu- 

 lar activating system back to the midbrain tegmentum 

 (51 ). \. clue to a possible way in which this may occur 

 is suggested by the studies of Green & Adey (45) and 

 Adey et al. (2) who found that stimulation of the 

 hippocampus evoked responses in the entorhinal area 

 in apparent opposition to the main known anatomical 

 course of axons in this region. However, von Euler 

 et al. (112) also obtained evidence that seizure dis- 

 charges might propagate ephaptically from the hippo- 

 campus, via dendritic processes (perhaps to the en- 

 torhinal cortex), and such propagation is not unlikely 

 in view of the observations of Bremer (2 1 ) on the 

 synchronization of strychnine seizures in the cord, 

 those of Gerard & Libet (37) on the caffeine wave in 

 the frog brain, and those of Rosenblueth & Cannon 

 (98) and Rosenblueth el al. (97) on seizure discharges 

 in the cat cortex. The conclusion may, indeed, be 

 drawn that seizure discharges propagate both by 

 axonal pathways, for example in the so-called reflex 

 epilepsies of Amantea (13), as was demonstrated long 

 ago by Bubnoff & Heidenhain (23), and by routes 

 which are not strictly anatomical pathways but 

 simply regions of contiguity. 



Liberson & Cadilhac (69) have carried out studies 

 on hippocampal seizures in the guinea pig. In par- 

 ticular, they have undertaken to measure seizure 

 thresholds in terms of number and duration, as well as 

 amplitude of applied pulses, and have observed direct 

 current shifts in hippocampal seizures, von Euler 

 et al. (112) also observed a direct current shift during 

 hippocampal after-di.scharges and found that the 

 dendritic layer tended to show a negative shift whereas 

 the axonal layer on the surface of the hippocampus 

 shifted in the opposite direction. Thus, the seizure 

 seems to induce a polarization of the cell somewhat 

 along the lines visualized by Gesell (40) or by Libet & 

 Gerard (71 ). 



