Journal of Neurophysiology, Vol 75, Issue 1 343-353, Copyright © 1996 by APS

ARTICLES

Functional alterations in the dentate gyrus after induction of long-term potentiation, kindling, and mossy fiber sprouting

G. Golarai and T. P. Sutula
Department of Neurology and Anatomy, University of Wisconsin, Madison 53792, USA.

1. The effects of long-term potentiation (LTP) and kindling on membrane currents evoked in the dentate gyrus (DG) by stimulation of the perforant path (PP) were studied by current-source density (CSD) analysis in urethan-anesthetized rats. The spatial and temporal patterns of the evoked currents were analyzed after induction of LTP, at 24 h after three afterdischarges (ADs) induced by kindling stimulation, and at 4-5 wk after 70-120 generalized tonic-clonic (class V) kindled seizures. 2. The amplitude of the ipsilateral monosynaptic population excitatory postsynaptic current (iEPSC) evoked in the middle and outer stratum moleculare (STM) of the DG by PP stimulation increased by 20-100% after induction of LTP (N = 7 of 7). There was a trend to shorter onset latency of the iEPSC after induction of LTP, but the duration and spatial distribution of the iEPSC were unchanged (N = 7 of 7). The latency of inward current generated by synchronous granule cell discharge during the population spike decreased by 0.5-1 ms after induction of LTP (N = 6 of 7). 3. There were no significant alterations in the spatial and temporal pattern of the monosynaptic iEPSC evoked by PP stimulation at 24 h after three ADs induced by kindling stimulation (N = 6 of 6), or at 4-5 wk after the last of 70-120 class V kindled seizures (N = 14 of 14). 4. The spatial and temporal distribution of low-amplitude inward currents generated after the population spike was not altered after induction of LTP (7 of 7), or at 24 h after three ADs induced by kindling stimulation (N = 6 of 6). In kindled rats studied at 4-5 wk after the last of 70-120 class V seizures, there was an alteration in evoked currents after the population spike consisting of a distinct peak of net inward current at a latency of 9-12 ms in the proximal STM (N = 10 of 14). Inward current at this latency and location was not observed in > 100 normal rats, in age-matched normal controls (N = 4 of 4), or after acute seizures induced by pentylenetetrazol (35 mg/kg ip, N = 5 of 5). 5. Timm histochemistry was combined with CSD analysis to examine the relationship of the inward current at 9-12 ms to the terminal field of the sprouted mossy fiber pathway, which forms asymmetric, putatively excitatory synapses in the inner STM of the DG in kindled rats. In six of eight kindled rats with sprouted mossy fiber terminals demonstrated by Timm histochemistry, CSD analysis revealed that the peak amplitude of the inward current colocalized with the laminar distribution of sprouted mossy fiber terminals. In the remaining two of the eight kindled rats with sprouted terminals in the inner STM, there was no alteration in the spatial and temporal distribution of inward current after the population spike. 6. In conclusion, LTP and kindling induced distinct alterations in currents evoked in the DG by stimulation of the PP. After induction of LTP, there was an acute increase in the amplitude of the monosynaptic iEPSC and reduction in the latency of currents associated with granule cell discharge, but there was no alteration in the spatial or temporal organization of multisynaptic activity. In contrast, long-lasting effects of kindling included an alteration in the spatial and temporal organization of multisynaptic currents, which was consistent with excitatory synaptic transmission by synaptic terminals of the sprouted mossy fiber pathway. The functional alterations induced by LTP and kindling may have implications for associative properties, information processing, and epileptogenesis in the DG.

This article has been cited by other articles:

				G. Golarai, A. C. Greenwood, D. M. Feeney, and J. A. Connor Physiological and Structural Evidence for Hippocampal Involvement in Persistent Seizure Susceptibility after Traumatic Brain Injury J. Neurosci., November 1, 2001; 21(21): 8523 - 8537. [Abstract] [Full Text] [PDF]

				J. Behr, U. Heinemann, and I. Mody Kindling Induces Transient NMDA Receptor-Mediated Facilitation of High-Frequency Input in the Rat Dentate Gyrus J Neurophysiol, May 1, 2001; 85(5): 2195 - 2202. [Abstract] [Full Text] [PDF]

				M. Lynch, U. Sayin, G. Golarai, and T. Sutula NMDA Receptor-Dependent Plasticity of Granule Cell Spiking in the Dentate Gyrus of Normal and Epileptic Rats J Neurophysiol, December 1, 2000; 84(6): 2868 - 2879. [Abstract] [Full Text] [PDF]

				M. Lynch and T. Sutula Recurrent Excitatory Connectivity in the Dentate Gyrus of Kindled and Kainic Acid-Treated Rats J Neurophysiol, February 1, 2000; 83(2): 693 - 704. [Abstract] [Full Text] [PDF]

				M. M. Okazaki, P. Molnar, and J. V. Nadler Recurrent Mossy Fiber Pathway in Rat Dentate Gyrus: Synaptic Currents Evoked in Presence and Absence of Seizure-Induced Growth J Neurophysiol, April 1, 1999; 81(4): 1645 - 1660. [Abstract] [Full Text] [PDF]

				U. Sayin, P. Rutecki, and T. Sutula NMDA-Dependent Currents in Granule Cells of the Dentate Gyrus Contribute to Induction but Not Permanence of Kindling J Neurophysiol, February 1, 1999; 81(2): 564 - 574. [Abstract] [Full Text] [PDF]

				P. S. Buckmaster and F. E. Dudek In Vivo Intracellular Analysis of Granule Cell Axon Reorganization in Epileptic Rats J Neurophysiol, February 1, 1999; 81(2): 712 - 721. [Abstract] [Full Text] [PDF]

				Y. Shoji, E. Tanaka, S. Yamamoto, H. Maeda, and H. Higashi Mechanisms Underlying the Enhancement of Excitatory Synaptic Transmission in Basolateral Amygdala Neurons of the Kindling Rat J Neurophysiol, August 1, 1998; 80(2): 638 - 646. [Abstract] [Full Text] [PDF]

				J. Behr, K. J. Lyson, and I. Mody Enhanced Propagation of Epileptiform Activity Through the Kindled Dentate Gyrus J Neurophysiol, April 1, 1998; 79(4): 1726 - 1732. [Abstract] [Full Text] [PDF]

				P. R. Patrylo and F. E. Dudek Physiological Unmasking of New Glutamatergic Pathways in the Dentate Gyrus of Hippocampal Slices From Kainate-Induced Epileptic Rats J Neurophysiol, January 1, 1998; 79(1): 418 - 429. [Abstract] [Full Text] [PDF]

				P. S. Buckmaster and F. E. Dudek Network Properties of the Dentate Gyrus in Epileptic Rats With Hilar Neuron Loss and Granule Cell Axon Reorganization J Neurophysiol, May 1, 1997; 77(5): 2685 - 2696. [Abstract] [Full Text] [PDF]

				T. Sutula, J. Koch, G. Golarai, Y. Watanabe, and J. O. McNamara NMDA Receptor Dependence of Kindling and Mossy Fiber Sprouting: Evidence that the NMDA Receptor Regulates Patterning of Hippocampal Circuits in the Adult Brain J. Neurosci., November 15, 1996; 16(22): 7398 - 7406. [Abstract] [Full Text] [PDF]