 |
 Previous Article | Next Article 
The Journal of Neuroscience, November 1, 1999, 19(21):9519-9529
Highly Specific Neuron Loss Preserves Lateral Inhibitory Circuits
in the Dentate Gyrus of Kainate-Induced Epileptic Rats
Paul S.
Buckmaster1 and
Ana L.
Jongen-Rêlo2
1 Departments of Comparative Medicine and Neurology and
Neurological Sciences, Stanford University School of Medicine,
Stanford, California 94305-5410, and 2 Behavioral Biology
Laboratory, Laboratory of Anatomy, Swiss Federal Institute of
Technology, Zurich, CH-8603, Schwerzenbach, Switzerland
Patients with temporal lobe epilepsy display neuron loss in the
hilus of the dentate gyrus. This has been proposed to be epileptogenic by a variety of different mechanisms. The present study examines the
specificity and extent of neuron loss in the dentate gyrus of
kainate-treated rats, a model of temporal lobe epilepsy.
Kainate-treated rats lose an average of 52% of their GAD-negative
hilar neurons (putative mossy cells) and 13% of their
GAD-positive cells (GABAergic interneurons) in the dentate gyrus.
Interneuron loss is remarkably specific; 83% of the missing
GAD-positive neurons are somatostatin-immunoreactive. Of the total
neuron loss in the hilus, 97% is attributed to two cell types mossy
cells and somatostatinergic interneurons. The retrograde tracer
wheat germ agglutinin (WGA)-apoHRP-gold was used to identify neurons
with appropriate axon projections for generating lateral inhibition.
Previously, it was shown that lateral inhibition between regions
separated by 1 mm persists in the dentate gyrus of kainate-treated rats
with hilar neuron loss. Retrogradely labeled GABAergic interneurons are
found consistently in sections extending 1 mm septotemporally
from the tracer injection site in control and kainate-treated rats.
Retrogradely labeled putative mossy cells are found up to 4 mm from the
injection site, but kainate-treated rats have fewer than controls, and
in several kainate-treated rats virtually all of these cells are
missing. These findings support hypotheses of temporal lobe
epileptogenesis that involve mossy cell and somatostatinergic neuron
loss and suggest that lateral inhibition in the dentate gyrus does not require mossy cells but, instead, may be generated directly by GABAergic interneurons.
Key words:
hippocampus; dentate gyrus; GABA; GAD; somatostatin; interneurons; inhibition; epilepsy
Copyright © 1999 Society for Neuroscience 0270-6474/99/19219519-11$05.00/0
This article has been cited by other articles:
|
|
|
|
 
W. Zhang, R. Yamawaki, X. Wen, J. Uhl, J. Diaz, D. A. Prince, and P. S. Buckmaster
Surviving Hilar Somatostatin Interneurons Enlarge, Sprout Axons, and Form New Synapses with Granule Cells in a Mouse Model of Temporal Lobe Epilepsy
J. Neurosci.,
November 11, 2009;
29(45):
14247 - 14256.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R.-Z. Zhan and J. V. Nadler
Enhanced Tonic GABA Current in Normotopic and Hilar Ectopic Dentate Granule Cells After Pilocarpine-Induced Status Epilepticus
J Neurophysiol,
August 1, 2009;
102(2):
670 - 681.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
W. Zhang and P. S. Buckmaster
Dysfunction of the Dentate Basket Cell Circuit in a Rat Model of Temporal Lobe Epilepsy
J. Neurosci.,
June 17, 2009;
29(24):
7846 - 7856.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. Larimer and B. W. Strowbridge
Nonrandom Local Circuits in the Dentate Gyrus
J. Neurosci.,
November 19, 2008;
28(47):
12212 - 12223.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J.-M. Mangin, A. Kunze, R. Chittajallu, and V. Gallo
Satellite NG2 Progenitor Cells Share Common Glutamatergic Inputs with Associated Interneurons in the Mouse Dentate Gyrus
J. Neurosci.,
July 23, 2008;
28(30):
7610 - 7623.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Knopp, C. Frahm, P. Fidzinski, O. W. Witte, and J. Behr
Loss of GABAergic neurons in the subiculum and its functional implications in temporal lobe epilepsy
Brain,
June 1, 2008;
131(6):
1516 - 1527.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. J. Morgan and I. Soltesz
From the Cover: Nonrandom connectivity of the epileptic dentate gyrus predicts a major role for neuronal hubs in seizures
PNAS,
April 22, 2008;
105(16):
6179 - 6184.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Epsztein, Y. Ben-Ari, A. Represa, and V. Crepel
Late-Onset Epileptogenesis and Seizure Genesis: Lessons From Models of Cerebral Ischemia
Neuroscientist,
February 1, 2008;
14(1):
78 - 90.
[Abstract]
[PDF]
|
|
|
|
|
|
|
B. Nahir, C. Bhatia, and C. J. Frazier
Presynaptic Inhibition of Excitatory Afferents to Hilar Mossy Cells
J Neurophysiol,
June 1, 2007;
97(6):
4036 - 4047.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y.-S. Choi, S. L. Lin, B. Lee, P. Kurup, H.-Y. Cho, J. R. Naegele, P. J. Lombroso, and K. Obrietan
Status Epilepticus-Induced Somatostatinergic Hilar Interneuron Degeneration Is Regulated by Striatal Enriched Protein Tyrosine Phosphatase
J. Neurosci.,
March 14, 2007;
27(11):
2999 - 3009.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. L. Howard, A. Neu, R. J. Morgan, J. C. Echegoyen, and I. Soltesz
Opposing Modifications in Intrinsic Currents and Synaptic Inputs in Post-Traumatic Mossy Cells: Evidence for Single-Cell Homeostasis in a Hyperexcitable Network
J Neurophysiol,
March 1, 2007;
97(3):
2394 - 2409.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Dyhrfjeld-Johnsen, V. Santhakumar, R. J. Morgan, R. Huerta, L. Tsimring, and I. Soltesz
Topological Determinants of Epileptogenesis in Large-Scale Structural and Functional Models of the Dentate Gyrus Derived From Experimental Data
J Neurophysiol,
February 1, 2007;
97(2):
1566 - 1587.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J.-s. Qi, J. Yao, C. Fang, B. Luscher, and G. Chen
Downregulation of tonic GABA currents following epileptogenic stimulation of rat hippocampal cultures
J. Physiol.,
December 1, 2006;
577(2):
579 - 590.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. Halabisky, F. Shen, J. R. Huguenard, and D. A. Prince
Electrophysiological Classification of Somatostatin-Positive Interneurons in Mouse Sensorimotor Cortex
J Neurophysiol,
August 1, 2006;
96(2):
834 - 845.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Epsztein, M. Milh, R. Id Bihi, I. Jorquera, Y. Ben-Ari, A. Represa, and V. Crepel
Ongoing epileptiform activity in the post-ischemic hippocampus is associated with a permanent shift of the excitatory-inhibitory synaptic balance in CA3 pyramidal neurons.
J. Neurosci.,
June 28, 2006;
26(26):
7082 - 7092.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
X. Jin, D. A. Prince, and J. R. Huguenard
Enhanced excitatory synaptic connectivity in layer v pyramidal neurons of chronically injured epileptogenic neocortex in rats.
J. Neurosci.,
May 3, 2006;
26(18):
4891 - 4900.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. S. Kumar and P. S. Buckmaster
Hyperexcitability, interneurons, and loss of GABAergic synapses in entorhinal cortex in a model of temporal lobe epilepsy.
J. Neurosci.,
April 26, 2006;
26(17):
4613 - 4623.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L.-R. Shao and F. E. Dudek
Changes in mIPSCs and sIPSCs After Kainate Treatment: Evidence for Loss of Inhibitory Input to Dentate Granule Cells and Possible Compensatory Responses
J Neurophysiol,
August 1, 2005;
94(2):
952 - 960.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
X. Jin, J. R. Huguenard, and D. A. Prince
Impaired Cl- Extrusion in Layer V Pyramidal Neurons of Chronically Injured Epileptogenic Neocortex
J Neurophysiol,
April 1, 2005;
93(4):
2117 - 2126.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Foldy, J. Dyhrfjeld-Johnsen, and I. Soltesz
Structure of cortical microcircuit theory
J. Physiol.,
January 1, 2005;
562(1):
47 - 54.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. J. Bough, D. D. Mott, and R. J. Dingledine
Medial Perforant Path Inhibition Mediated by mGluR7 Is Reduced After Status Epilepticus
J Neurophysiol,
September 1, 2004;
92(3):
1549 - 1557.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. d. H. Ratzliff, A. L. Howard, V. Santhakumar, I. Osapay, and I. Soltesz
Rapid Deletion of Mossy Cells Does Not Result in a Hyperexcitable Dentate Gyrus: Implications for Epileptogenesis
J. Neurosci.,
March 3, 2004;
24(9):
2259 - 2269.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. A. Zappone and R. S. Sloviter
Translamellar Disinhibition in the Rat Hippocampal Dentate Gyrus after Seizure-Induced Degeneration of Vulnerable Hilar Neurons
J. Neurosci.,
January 28, 2004;
24(4):
853 - 864.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. E. Scharfman, A. L. Sollas, R. E. Berger, and J. H. Goodman
Electrophysiological Evidence of Monosynaptic Excitatory Transmission Between Granule Cells After Seizure-Induced Mossy Fiber Sprouting
J Neurophysiol,
October 1, 2003;
90(4):
2536 - 2547.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Kobayashi, X. Wen, and P. S. Buckmaster
Reduced Inhibition and Increased Output of Layer II Neurons in the Medial Entorhinal Cortex in a Model of Temporal Lobe Epilepsy
J. Neurosci.,
September 17, 2003;
23(24):
8471 - 8479.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Kobayashi and P. S. Buckmaster
Reduced Inhibition of Dentate Granule Cells in a Model of Temporal Lobe Epilepsy
J. Neurosci.,
March 15, 2003;
23(6):
2440 - 2452.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. S. Buckmaster, G. F. Zhang, and R. Yamawaki
Axon Sprouting in a Model of Temporal Lobe Epilepsy Creates a Predominantly Excitatory Feedback Circuit
J. Neurosci.,
August 1, 2002;
22(15):
6650 - 6658.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Q.-Q. Sun, J. R. Huguenard, and D. A. Prince
Somatostatin Inhibits Thalamic Network Oscillations In Vitro: Actions on the GABAergic Neurons of the Reticular Nucleus
J. Neurosci.,
July 1, 2002;
22(13):
5374 - 5386.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. R. Patrylo, D. D. Spencer, and A. Williamson
GABA Uptake and Heterotransport Are Impaired in the Dentate Gyrus of Epileptic Rats and Humans With Temporal Lobe Sclerosis
J Neurophysiol,
April 1, 2001;
85(4):
1533 - 1542.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. L. Hardison, M. M. Okazaki, and J. V. Nadler
Modest Increase in Extracellular Potassium Unmasks Effect of Recurrent Mossy Fiber Growth
J Neurophysiol,
November 1, 2000;
84(5):
2380 - 2389.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. Acsady, I. Katona, F. J. Martinez-Guijarro, G. Buzsaki, and T. F. Freund
Unusual Target Selectivity of Perisomatic Inhibitory Cells in the Hilar Region of the Rat Hippocampus
J. Neurosci.,
September 15, 2000;
20(18):
6907 - 6919.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. S. Buckmaster, A. L. Jongen-Relo, S. B. Davari, and E. H. Wong
Testing the Disinhibition Hypothesis of Epileptogenesis In Vivo and during Spontaneous Seizures
J. Neurosci.,
August 15, 2000;
20(16):
6232 - 6240.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
