Morpho-functional characterization of neuronal cells at different stages of maturation in granule cell layer of adult rat dentate gyrus

Ambrogini, Patrizia; Lattanzi, Davide; Ciuffoli, Stefano; Agostini, Deborah; Bertini, L.; Stocchi, Vilberto; Santi, Spartaco; Cuppini, Riccardo

doi:10.1016/j.brainres.2004.05.039

Cited by 191 publications

(207 citation statements)

References 23 publications

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“…In addition, the intact basal synaptic efficacy at both input and output synapses of the fluoxetine-treated GCs implies that the formation of synaptic connection itself was preserved. Young GCs generated during the fluoxetine treatment would be smaller and have higher input resistance than mature cells (12,14,16), and would have less synaptic contacts (16). Thus, these results are consistent with the idea that the immature-like GCs in fluoxetine-treated mice mostly originated from mature cells.…”

Section: Discussionsupporting

confidence: 80%

“…In comparison with mature cells, young GCs can be more easily excited by somatic current injection, because they have higher input resistance and can generate tetrodotoxin (TTX)-resistant, but Ni 2+ -senstive, low-threshold spikes that can boost sodium spikes (12,14). Fluoxetine-treated GCs were more excitable ( Fig.…”

Section: Fluoxetine-treated Granule Cells Exhibit Immature-like Functmentioning

confidence: 99%

“…The dentate gyrus is positioned at the entrance of the hippocampal excitatory trisynaptic circuit, and the mossy fiber (MF) from the DG plays a critical role in regulating associative synaptic plasticity in the hippocampal CA3 region (9,10). Because physiological properties of granule cells (GCs), the principal neurons of the DG, greatly change with development or neuronal maturation (11)(12)(13)(14)(15)(16), an increase in a proportion of relatively young GCs by facilitated neurogenesis may alter functional roles of the DG in the hippocampal circuit. However, the majority of the neuronal population in adult DG is composed of mature GCs.…”

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confidence: 99%

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Reversal of hippocampal neuronal maturation by serotonergic antidepressants

Kobayashi

Ikeda

Sakai

et al. 2010

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

191

275

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Serotonergic antidepressant drugs have been commonly used to treat mood and anxiety disorders, and increasing evidence suggests potential use of these drugs beyond current antidepressant therapeutics. Facilitation of adult neurogenesis in the hippocampal dentate gyrus has been suggested to be a candidate mechanism of action of antidepressant drugs, but this mechanism may be only one of the broad effects of antidepressants. Here we show a distinct unique action of the serotonergic antidepressant fluoxetine in transforming the phenotype of mature dentate granule cells. Chronic treatments of adult mice with fluoxetine strongly reduced expression of the mature granule cell marker calbindin. The fluoxetine treatment induced active somatic membrane properties resembling immature granule cells and markedly reduced synaptic facilitation that characterizes the mature dentate-to-CA3 signal transmission. These changes cannot be explained simply by an increase in newly generated immature neurons, but best characterized as "dematuration" of mature granule cells. This granule cell dematuration developed along with increases in the efficacy of serotonin in 5-HT 4 receptor-dependent neuromodulation and was attenuated in mice lacking the 5-HT 4 receptor. Our results suggest that serotonergic antidepressants can reverse the established state of neuronal maturation in the adult hippocampus, and up-regulation of 5-HT 4 receptor-mediated signaling may play a critical role in this distinct action of antidepressants. Such reversal of neuronal maturation could affect proper functioning of the mature hippocampal circuit, but may also cause some beneficial effects by reinstating neuronal functions that are lost during development. dentate gyrus | development | mossy fiber | serotonin receptor | serotonin reuptake inhibitor

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Section: Discussionsupporting

confidence: 80%

Section: Fluoxetine-treated Granule Cells Exhibit Immature-like Functmentioning

confidence: 99%

mentioning

confidence: 99%

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Reversal of hippocampal neuronal maturation by serotonergic antidepressants

Kobayashi

Ikeda

Sakai

et al. 2010

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

191

275

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“…Certain characteristics of synaptic plasticity are enhanced in adult-generated neurons and these characteristics may make them particularly useful for the processing of new associations. The induction threshold for LTP is lower for young granule cells in the DG and is also insensitive to GABAergic inhibition (Wang et al, 2000;Snyder et al, 2001;Ambrogini et al, 2004b;Schmidt-Hieber et al, 2004). Whether adult-generated cells retain these properties after they achieve maturity remains to be determined.…”

Section: How Might New Neurons Participate In Learning and Memory?mentioning

confidence: 99%

“…At an information processing level, how does a new population of neurons interact with those neurons that were generated during development and how do these interactions lead to the formation of new memories without destroying old memories? Addressing most of these questions will require a better understanding of the functional maturation of adultgenerated neurons (Carlen et al, 2002;Dayer et al, 2003;Ambrogini et al, 2004b) as well as insight into the differences and similarities between neurons generated during development vs. those produced in adulthood. Until now, addressing such issues has been inhibited by technical limitations but may be more feasible given a number of recent advances.…”

Section: Future Directionsmentioning

confidence: 99%

Is there a link between adult neurogenesis and learning?

2006

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During the past several years, evidence has accumulated suggesting a relationship between newly born cells in the hippocampus and various types of learning and memory. However, most of the evidence is correlational and some of it does not agree. This review discusses both sides of this issue, considering the effects of learning on the production of new neurons in the dentate gyrus and the question of whether newly born cells participate in learning and memory.

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