Dendritic Integration in Hippocampal Dentate Granule Cells

Krueppel, Roland; Remy, Stefan; Beck, Hanno

doi:10.1016/j.neuron.2011.05.043

Cited by 193 publications

(253 citation statements)

References 45 publications

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“…In their studies, V rest of DGCs remains at ϳϪ60 mV throughout all developmental stages, whereas E GABA shifts from ϳϪ40 to ϳϪ70 mV during development. In contrast, several other groups have found that DGCs have very negative V rest (from Ϫ80 to Ϫ85 mV) both in vitro (Staley and Mody, 1992;Schmidt-Hieber et al, 2004Alle and Geiger, 2006;Krueppel et al, 2011) and in vivo (Penttonen et al, 1997).…”

Section: Determining Gabaergic Actions Using a Noninvasive Approachmentioning

confidence: 70%

GABA Is Depolarizing in Hippocampal Dentate Granule Cells of the Adolescent and Adult Rats

Chiang¹,

Wu²,

Kuo³

et al. 2012

J. Neurosci.

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GABAergic signaling in hippocampal pyramidal neurons undergoes a switch from depolarizing to hyperpolarizing during early neuronal development. Whether such a transformation of GABAergic action occurs in dentate granule cells (DGCs), located at the first stage of the hippocampal trisynaptic circuit, is unclear. Here, we use noninvasive extracellular recording to monitor the effect of synaptically released GABA on the DGC population. We find that GABAergic responses in adolescent and adult rat DGCs are still depolarizing from rest. Using a morphologically realistic DGC model, we show that GABAergic action, depending on its precise timing and location, can have either an excitatory or inhibitory role in signal processing in the dentate gyrus.

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Section: Determining Gabaergic Actions Using a Noninvasive Approachmentioning

confidence: 70%

GABA Is Depolarizing in Hippocampal Dentate Granule Cells of the Adolescent and Adult Rats

Chiang¹,

Wu²,

Kuo³

et al. 2012

J. Neurosci.

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“…DG PCs receive excitatory inputs from the perforant path (PP) at their apical distal dendrites, electrotonically distant from the cell body. Thus, PP-mediated signals are strongly attenuated until they reach the soma (Krueppel et al, 2011). Furthermore, the voltage difference between the resting potential and spike threshold is large and has to be traversed to generate action potentials.…”

Section: Discussionmentioning

confidence: 99%

Interneurons Provide Circuit-Specific Depolarization and Hyperpolarization

Sauer

Strüber²,

Bartos³

2012

J. Neurosci.

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Perisoma-inhibiting interneurons (PIIs) control fundamental aspects of cortical network function by means of their GABAergic output synapses. However, whether they depolarize or hyperpolarize their target cells in the mature circuitry remains controversial. By using unitary field potential and gramicidin D perforated-patch recordings, we provide evidence that the postsynaptic effect of GABAergic synapses is fundamentally different in two regions of rat hippocampus. Signaling at PII output synapses is hyperpolarizing in CA1 principal cells (PCs) but depolarizing in dentate gyrus (DG) PCs. While the reversal potential of GABA A receptor-mediated currents is identical in both areas, ϳ15 mV more negative resting potentials of DG compared with CA1 PCs underlie the opposing effects of perisomatic GABAergic transmission. Thus, the nature of PII output signaling is circuit-dependent and may therefore contribute differentially to information processing in the two brain areas.

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“…To assess basal synaptic transmission in Pten cKO mice, we stimulated afferents in the medial perforant pathway and monitored the input/output relation of field excitatory postsynaptic potentials (fEPSPs) at synapses on DGCs. We focused on the DG because it is a critical checkpoint for the flow of information from the entorhinal cortex to the hippocampus (25) and exhibits progressive neuronal hypertrophy in Pten cKO mice by 14 wk of age (15). The input/output relation (fEPSP slope vs. stimulus intensity) at DGC synapses was unaltered in young (8-12 wk) and old (20-30 wk) Pten cKO mice, but enhanced in middle-aged (14-19 wk) Pten cKO mice relative to that of age-matched WT mice ( Fig.…”

Section: Basal Synaptic Transmission At Dgc Synapses Is Enhanced In Mmentioning

confidence: 99%

Dysregulation of synaptic plasticity precedes appearance of morphological defects in a Pten conditional knockout mouse model of autism

Takeuchi

Gertner

Zhou

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

114

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The phosphoinositide signaling system is a crucial regulator of neural development, cell survival, and plasticity. Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) negatively regulates phosphatidylinositol 3-kinase signaling and downstream targets. Nse-Cre Pten conditional knockout mice, in which Pten is ablated in granule cells of the dentate gyrus and pyramidal neurons of the hippocampal CA3, but not CA1, recapitulate many of the symptoms of humans with inactivating PTEN mutations, including progressive hypertrophy of the dentate gyrus and deficits in hippocampus-based social and cognitive behaviors. However, the impact of Pten loss on activity-dependent synaptic plasticity in this clinically relevant mouse model of Pten inactivation remains unclear. Here, we show that two phosphatidylinositol 3-kinase-and protein synthesis-dependent forms of synaptic plasticity, theta burstinduced long-term potentiation and metabotropic glutamate receptor (mGluR)-dependent long-term depression, are dysregulated at medial perforant path-to-dentate gyrus synapses of young NseCre Pten conditional knockout mice before the onset of visible morphological abnormalities. In contrast, long-term potentiation and mGluR-dependent long-term depression are normal at CA3-CA1 pyramidal cell synapses at this age. Our results reveal that deletion of Pten in dentate granule cells dysregulates synaptic plasticity, a defect that may underlie abnormal social and cognitive behaviors observed in humans with Pten inactivating mutations and potentially other autism spectrum disorders.T he discovery of genes associated with autism spectrum disorders (ASDs) has largely depended on gene linkage analyses within lineages of humans with familial ASDs (1-3). A well-established candidate gene is the tumor-suppressor gene, phosphatase and tensin homolog missing on chromosome 10 (PTEN) (4-7). Pten is a lipid and protein phosphatase best known for its role in suppressing tumor formation by inhibiting cellular survival, proliferation, and cellular architecture (8, 9), but which also plays an important role in brain morphology and synaptic function (10, 11). Pten acts via its lipid phosphatase activity to dephosphorylate phosphatidylinositol (3,4,5)-trisphosphate and negatively regulate the PI3K-mammalian target of rapamycin (mTOR) signaling pathway. Although PTEN mutations are present in 5-10% of people with ASDs (12-14), loss-of-function point mutations in this gene give rise to progressive macrocephaly, a hallmark feature that occurs in nearly 20% of humans with ASDs (5, 6). In addition to anatomical abnormalities, humans with inactivating PTEN mutations exhibit spontaneous seizures and deficits in social and cognitive behaviors (10, 11).A conditional Pten knockout mouse (cKO) in which both alleles of the Pten gene contain loxP sites and Cre recombinase (Cre) is expressed under the neuron-specific enolase promoter (Nse-Cre) provides a clinically relevant mouse model for humans with inactivating PTEN mutations (15). In Nse-Cre Pten cKO (hereafter P...

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Dendritic Integration in Hippocampal Dentate Granule Cells

Cited by 193 publications

References 45 publications

GABA Is Depolarizing in Hippocampal Dentate Granule Cells of the Adolescent and Adult Rats

GABA Is Depolarizing in Hippocampal Dentate Granule Cells of the Adolescent and Adult Rats

Interneurons Provide Circuit-Specific Depolarization and Hyperpolarization

Dysregulation of synaptic plasticity precedes appearance of morphological defects in a Pten conditional knockout mouse model of autism

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