J. J. M. and S. L. B. contributed equally to this work.
Altered patterning of dentate granule cell mossy fiber inputs onto CA3 pyramidal cells in limbic epilepsy
Article first published online: 15 DEC 2009
Copyright © 2010 Wiley-Liss, Inc.
Volume 21, Issue 1, pages 93–107, January 2011
How to Cite
McAuliffe, J. J., Bronson, S. L., Hester, M. S., Murphy, B. L., Dahlquist-Topalá, R., Richards, D. A. and Danzer, S. C. (2011), Altered patterning of dentate granule cell mossy fiber inputs onto CA3 pyramidal cells in limbic epilepsy. Hippocampus, 21: 93–107. doi: 10.1002/hipo.20726
- Issue published online: 15 DEC 2009
- Article first published online: 15 DEC 2009
- Manuscript Accepted: 21 SEP 2009
- National Institute of Neurological Disorders and Stroke. Grant Numbers: R01-NS-065020, R01-NS-062806
- Cincinnati Children's Hospital Medical Center
- Epilepsy Foundation of America
- thorny excrescence;
- synaptic plasticity;
Impaired gating by hippocampal dentate granule cells may promote the development of limbic epilepsy by facilitating seizure spread through the hippocampal trisynaptic circuit. The second synapse in this circuit, the dentate granule cell≫CA3 pyramidal cell connection, may be of particular importance because pathological changes occurring within the dentate likely exert their principal effect on downstream CA3 pyramids. Here, we utilized GFP-expressing mice and immunolabeling for the zinc transporter ZnT-3 to reveal the pre- and postsynaptic components of granule cell≫CA3 pyramidal cell synapses following pilocarpine-epileptogenesis. Confocal analyses of these terminals revealed that while granule cell presynaptic giant boutons increased in size and complexity 1 month after status epilepticus, individual thorns making up the postsynaptic thorny excrescences of the CA3 pyramidal cells were reduced in number. This reduction, however, was transient, and 3 months after status, thorn density recovered. This recovery was accompanied by a significant change in the distribution of thorns along pyramidal cells dendrites. While thorns in control animals tended to be tightly clustered, thorns in epileptic animals were more evenly distributed. Computational modeling of thorn distributions predicted an increase in the number of boutons required to cover equivalent numbers of thorns in epileptic vs. control mice. Confirming this prediction, ZnT-3 labeling of presynaptic giant boutons apposed to GFP-expressing thorns revealed a near doubling in bouton density, while the number of individual thorns per bouton was reduced by half. Together, these data provide clear evidence of novel plastic changes occurring within the epileptic hippocampus. © 2009 Wiley-Liss, Inc.