Disruption of PLC-$beta;1-Mediated Signal Transduction in Mutant Mice Causes Age-Dependent Hippocampal Mossy Fiber Sprouting and Neurodegeneration

Neurogenesis in the dentate gyrus (DG) has attracted attention since abnormal supragranular mossy fiber sprouting occurs in the same region, in temporal lobe epilepsy. Thus, we submitted developing rats to pilocarpine-induced status epilepticus (SE) to study the relationship between neurogenesis and mossy fiber sprouting. Groups were submitted to SE at: I-P9, II-P7, P8 and P9, III-P17 e IV-P21. Neurogenesis was quantified using BrdU protocol and confirmed through double staining, using neuronal pentraxin. Other animals were monitored by video system until P120 and their brain was studied (Timm and Nissl staining). The neurogenesis at P17 (p=0.007) and P21 (p=0.006) were increased. However, only P21 group showed recurrent seizures and the mossy fiber sprouting in the same region, during adult life, while P17 did not. Thus, our results suggest that neurogenesis is not related to mossy fiber sprouting neither to recurrent spontaneous seizures in pilocarpine model.

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Time course of mossy fiber sprouting following bilateral transection of the fimbria/fornix

Neuroreport ◽

10.1097/00001756-199707070-00040 ◽

1997 ◽

Vol 8 (9) ◽

pp. 2299-2303 ◽

Cited By ~ 7

Author(s):

Darren K. Hannesson ◽

Lisa L. Armitage ◽

Paul Mohapel ◽

Michael E. Corcoran

Keyword(s):

Time Course ◽

Mossy Fiber ◽

Mossy Fiber Sprouting

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Mossy fiber sprouting is dissociated from kindling of generalized seizures in the guinea-pig

Neuroreport ◽

10.1097/00001756-200009110-00014 ◽

2000 ◽

Vol 11 (13) ◽

pp. 2897-2901 ◽

Cited By ~ 16

Author(s):

Paul Mohapel ◽

Lisa L. Armitage ◽

Trevor H. Gilbert ◽

Darren K. Hannesson ◽

G Campbell Teskey ◽

...

Keyword(s):

Guinea Pig ◽

Mossy Fiber ◽

Mossy Fiber Sprouting ◽

Generalized Seizures

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Regionally Localized Recurrent Excitation in the Dentate Gyrus of a Cortical Contusion Model of Posttraumatic Epilepsy

Journal of Neurophysiology ◽

10.1152/jn.00957.2009 ◽

2010 ◽

Vol 103 (3) ◽

pp. 1490-1500 ◽

Cited By ~ 46

Author(s):

Robert F. Hunt ◽

Stephen W. Scheff ◽

Bret N. Smith

Keyword(s):

Head Injury ◽

Dentate Gyrus ◽

Action Potentials ◽

Granule Cells ◽

Mossy Fiber ◽

Granule Cell Layer ◽

Mossy Fiber Sprouting ◽

Posttraumatic Epilepsy ◽

Dentate Granule Cells ◽

Cortical Contusion

Posttraumatic epilepsy is a frequent consequence of brain trauma, but relatively little is known about how neuronal circuits are chronically altered after closed head injury. We examined whether local recurrent excitatory synaptic connections form between dentate granule cells in mice 8–12 wk after cortical contusion injury. Mice were monitored for behavioral seizures shortly after brain injury and ≤10 wk postinjury. Injury-induced seizures were observed in 15% of mice, and spontaneous seizures were observed weeks later in 40% of mice. Timm's staining revealed mossy fiber sprouting into the inner molecular layer of the dorsal dentate gyrus ipsilateral to the injury in 95% of mice but not contralateral to the injury or in uninjured controls. Whole cell patch-clamp recordings were made from granule cells in isolated hippocampal brain slices. Cells in slices with posttraumatic mossy fiber sprouting had an increased excitatory postsynaptic current (EPSC) frequency compared with cells in slices without sprouting from injured and control animals ( P < 0.001). When perfused with Mg2+-free artificial cerebrospinal fluid containing 100 μM picrotoxin, these cells had spontaneous bursts of EPSCs and action potentials. Focal glutamate photostimulation of the granule cell layer evoked a burst of EPSCs and action potentials indicative of recurrent excitatory connections in granule cells of slices with mossy fiber sprouting. In granule cells of slices without sprouting from injured animals and controls, spontaneous or photostimulation-evoked epileptiform activity was never observed. These results suggest that a new regionally localized excitatory network forms between dentate granule cells near the injury site within weeks after cortical contusion head injury.

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