FUNCTIONAL ALTERATIONS IN THE DENTATE GYRUS AFTER INDUCTION OF LONG-TERM
POTENTIATION, KINDLING, AND MOSSY FIBER SPROUTING.
Golarai, Golijeh, Thomas P. Sutula.
The Neuroscience Training Program, and the Departments of Neurology,
Anatomy, University of Wisconsin, Madison, WI 53792, USA.
APStracts 2:0254N, 1995.
SUMMARY AND CONCLUSIONS
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 urethane
anaesthetized rats. The spatial and temporal patterns of the evoked currents
were analyzed after induction of LTP, at 24 hours after 3 afterdischarges
(ADs) induced by kindling stimulation, and at 4-5 weeks 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=7/7). 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=7/7). 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=6/7). 3- There were no significant alterations in the spatial and temporal
pattern of the monosynaptic iEPSC evoked by PP stimulation at 24 hours after 3
ADs induced by kindling stimulation (N=6/6), or at 4-5 weeks after the last of
70-120 Class V kindled seizures (N=14/14). 4- The spatial and temporal
distribution of low amplitude inward currents generated after the population
spike was not altered after induction of LTP (7/7), or at 24 hours after 3 ADs
induced by kindling stimulation (N=6/6). In kindled rats studied at 4-5 weeks
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=10/14). Inward
current at this latency and location was not observed in more than 100 normal
rats, in age-matched normal controls (N=4/4), or after acute seizures induced
by pentylenetetrazol (35mg/kg IP, N=5/5). 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 6 of 8 kindled rats with sprouted mossy fiber terminals
demonstrated by Timm histochemistry, CSD analysis revealed that the peak
amplitude of the inward current co-localized with the laminar distribution of
sprouted mossy fiber terminals. In the remaining 2 of the 8 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.
Received 3 February 1995; accepted in final form 7 August 1995.
APS Manuscript Number J72-5.
Article publication pending J. Neurophysiol.
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 24 August 1995.