Correlated Axonal Sprouting and Dendritic Spine Formation during Kainate-Induced Neuronal Morphogenesis in the Dentate Gyrus of Adult Mice

Suzuki, Fumio; Makiura, Yaeko; Guilhem, D.; Sørensen, J.C.; Onténiente, Brigitte

doi:10.1006/exnr.1997.6469

Cited by 61 publications

(53 citation statements)

References 45 publications

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“…1 F), these immature GABAergic BCs had smaller fusiform cell soma (ϳ20 -30 m) with smaller dendritic trees. These immature interneurons were rarely covered with spine structures, consistent with a previous study showing that mature spine and dendritic structures of central neurons are first evident 4 weeks after birth (Suzuki et al, 1997).…”

Section: Resultssupporting

confidence: 91%

Generation of Functional Inhibitory Neurons in the Adult Rat Hippocampus

et al. 2003

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Several thousand new neurons are produced each day in the adult mammalian hippocampus, among which only excitatory granule cells (GCs) have thus far been identified. In the present study, we used mutant Semliki Forest Virus vectors to express enhanced green fluorescent protein in the hippocampus, and observed that ϳ14% of newly generated neurons in the dentate gyrus of adult rats are GABAergic basket cells (BCs). With the use of double whole-cell patch-clamp recordings from BC-GC pairs in hippocampal slices, we demonstrate that newly generated BCs in the dentate gyrus form inhibitory synapses with principal GCs. These data show for the first time that functional inhibitory neurons are recruited in the dentate gyrus of adult rats.

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Section: Resultssupporting

confidence: 91%

Generation of Functional Inhibitory Neurons in the Adult Rat Hippocampus

et al. 2003

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“…Similar to the clinical findings, a loss of dendritic spines and varicose swelling of dendrites is frequently found in histological sections obtained from rats that had acute seizures or chronic epilepsy induced in vivo by various methods, such as convulsant drugs or electrical kindling [60][61][62][63][64][65], although rarely an increase in dendrites or spines has been reported [66][67][68]. Furthermore, spine loss and other dendritic changes can also occur with in vitro seizure models involving epileptiform bursting in brain slice-cultures [69][70][71][72].…”

Section: Dendritic Abnormalities In Epilepsysupporting

confidence: 63%

Stabilizing dendritic structure as a novel therapeutic approach for epilepsy

Wong¹

2008

Expert Review of Neurotherapeutics

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SummaryPeople with epilepsy often experience long-term cognitive dysfunction and other neurological deficits, including memory loss, learning disabilities, and neurobehavioral disorders, which may exhibit a progressive course correlating with worsening seizure control. Furthermore, one-third of epilepsy patients have seizures that are intractable to all available treatments. Thus, novel therapies for seizures and the neurological comorbidities of epilepsy are desperately needed. As most current treatments are merely "symptomatic" therapies that suppress seizures, recently epilepsy researchers have realized the critical need for novel therapeutic strategies targeting the underlying mechanisms of epileptogenesis and seizure-related brain injury. Yet to date, few such "anti-epileptogenic" therapies have emerged or are even in developmental stages. Although many seizure medications modulate the functional or physiological activity of neurons, a relatively unexplored therapeutic strategy for epilepsy are methods for stabilizing the structure of neurons. Human pathological studies and animal models of epilepsy demonstrate obvious structural abnormalities in dendrites of neurons, which could contribute to neuronal dysfunction, epileptogenesis, and cognitive/neurological deficits in epilepsy patients. This dendritic injury may be caused by activity-dependent breakdown of cytoskeletal elements, such as actin. Mechanistically-targeted approaches to limit seizure-related structural changes in dendrites may represent a novel therapeutic strategy for treating epilepsy and its complications.

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“…The large sample size needed to detect the minor increment in spine numbers was easily obtained in our study based on YFP expression in transgenic mice, compared with the cumbersome tracer injection techniques used previously. An increase of spine density in the dentate gyrus has previously been viewed as a structural basis for recurrent excitation and abnormal circuit function in kainate-induced epilepsy (Tauck and Nadler, 1985;Suzuki et al, 1997;Wuarin and Dudek, 2001). As such, our study adds new dimensions to the structural changes of both astrocytes and dendrites that accompany a model of posttraumatic epilepsy.…”

Section: Discussionmentioning

confidence: 99%

Loss of Astrocytic Domain Organization in the Epileptic Brain

et al. 2008

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Gliosis is a pathological hallmark of posttraumatic epileptic foci, but little is known about these reactive astrocytes beyond their high glial fibrillary acidic protein (GFAP) expression. Using diolistic labeling, we show that cortical astrocytes lost their nonoverlapping domain organization in three mouse models of epilepsy: posttraumatic injury, genetic susceptibility, and systemic kainate exposure. Neighboring astrocytes in epileptic mice showed a 10-fold increase in overlap of processes. Concurrently, spine density was increased on dendrites of excitatory neurons. Suppression of seizures by the common antiepileptic, valproate, reduced the overlap of astrocytic processes. Astrocytic domain organization was also preserved in APP transgenic mice expressing a mutant variant of human amyloid precursor protein despite a marked upregulation of GFAP. Our data suggest that loss of astrocytic domains was not universally associated with gliosis, but restricted to seizure pathologies. Reorganization of astrocytes may, in concert with dendritic sprouting and new synapse formation, form the structural basis for recurrent excitation in the epileptic brain.

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Correlated Axonal Sprouting and Dendritic Spine Formation during Kainate-Induced Neuronal Morphogenesis in the Dentate Gyrus of Adult Mice

Cited by 61 publications

References 45 publications

Generation of Functional Inhibitory Neurons in the Adult Rat Hippocampus

Generation of Functional Inhibitory Neurons in the Adult Rat Hippocampus

Stabilizing dendritic structure as a novel therapeutic approach for epilepsy

Loss of Astrocytic Domain Organization in the Epileptic Brain

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