Epileptogenesis Is Associated With Enhanced Glutamatergic Transmission in the Perforant Path

Scimemi, Annalisa; Schorge, Stephanie; Kullmann, Dimitri M.; Walker, Matthew C.

doi:10.1152/jn.00680.2005

Cited by 59 publications

(44 citation statements)

References 58 publications

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“…Thus, MPP synapses on newborn granule cells had prolonged and large NMDA receptormediated components characteristic of immature excitatory synapses (Carmignoto and Vicini, 1992;Tovar and Westbrook, 1999). Similar to previous reports (Sayin et al, 1999;Behr et al, 2001;Scimemi et al, 2006), mature granule cells also had larger NMDA EPSCs after seizures, even when polysynaptic input was blocked (242 Ϯ 43 pA, n ϭ 8, vs 69 Ϯ 16 pA, n ϭ 7; p ϭ 0.004) (Fig. 4b,c).…”

Section: Newborn Granule Cells Receive Direct and Recurrent Perforantsupporting

confidence: 88%

Seizures Accelerate Functional Integration of Adult-Generated Granule Cells

Overstreet-Wadiche¹,

Bromberg²,

Bensen³

et al. 2006

J. Neurosci.

232

224

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In humans and experimental animals, structural and functional changes in neural circuits can accompany the development of epilepsy. In the dentate gyrus, seizures enhance adult neurogenesis, but it is unclear to what extent newborn granule cells participate in seizureinduced synaptic reorganization. During the first weeks of their existence, mouse newborn granule cells labeled with enhanced green fluorescent protein have only short dendrites that lack excitatory input. We report that pilocarpine-induced seizures accelerated the morphological development of labeled granule cells, causing their dendrites to extend through the molecular layer. In whole-cell recordings 5-16 d after seizure induction, perforant-path stimulation now evoked glutamatergic input to newborn granule cells. These synaptic responses were mediated by monosynaptic as well as recurrent polysynaptic input. Thus, seizures facilitated functional integration of adult-generated granule cells. One month later, subsequent generations of newborn cells also showed alterations in dendrite morphology, suggesting persistent effects of seizures on granule cell maturation. The sensitivity of newborn granule cells to seizures could contribute to hyperexcitability during the latent period.

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Section: Newborn Granule Cells Receive Direct and Recurrent Perforantsupporting

confidence: 88%

Seizures Accelerate Functional Integration of Adult-Generated Granule Cells

Overstreet-Wadiche¹,

Bromberg²,

Bensen³

et al. 2006

J. Neurosci.

232

224

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“…Interestingly, increased release probability has also been described in other preparations where overall levels of activity are increased, after chemically induced seizures or in cortical dysplasia (Scimemi et al 2006;Yang et al 2006;Chen et al 2007;Upreti et al 2012) but see Pitsch et al (2012). The changes that are reported here are anti-homeostatic; they do not act to dampen the excitability of neurons in the face of increased sensory-evoked activity.…”

Section: Sre Changes Presynaptic Properties: Enhancing Releasesupporting

confidence: 68%

Experience-dependent regulation of presynaptic NMDARs enhances neurotransmitter release at neocortical synapses

et al. 2014

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Sensory experience can selectively alter excitatory synaptic strength at neocortical synapses. The rapid increase in synaptic strength induced by selective whisker stimulation (single-row experience/SRE, where all but one row of whiskers has been removed from the mouse face) is due, at least in part, to the trafficking of AMPA receptors (AMPARs) to the post-synaptic membrane, and is developmentally regulated. How enhanced sensory experience can alter presynaptic release properties in the developing neocortex has not been investigated. Using paired-pulse stimulation at layer 4-2/3 synapses in acute brain slices, we found that presynaptic release probability progressively increases in the spared-whisker barrel column over the first 24 h of SRE. Enhanced release probability can be at least partly attributed to presynaptic NMDA receptors (NMDARs). We find that the influence of presynaptic NMDARs in enhancing EPSC amplitude markedly increases during SRE. This occurs at the same time when recently potentiated synapses become highly susceptible to a NMDAR-dependent form of synaptic depression, during the labile phase of plasticity. Thus, these data show that augmented sensory stimulation can enhance release probability at layer 4-2/3 synapses and enhance the function of presynaptic NMDARs. Because presynaptic NMDARs have been linked to synaptic depression at layer 4-2/3 synapses, we propose that SRE-dependent up-regulation of presynaptic NMDARs is responsible for enhanced synaptic depression during the labile stage of plasticity.

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“…Thus, the seizureinduced sequence of changes in microglial morphology could be attenuated [25]. According to Scimemi et al [26], this process of gradual deramification of microglia was accompanied by increased neuronal excitability and recurrent mossy fibers sprouting [27,28] which resulted in an additional seizure activity. Nevertheless, in animals experiencing inflammation on postnatal day 6, similar transformations of microglia did not correspond with a significant modification in seizure activity.…”

Section: Discussionmentioning

confidence: 99%