Low excitatory innervation balances high intrinsic excitability of immature dentate neurons

Dieni, Cristina V.; Panichi, Roberto; Aimone, James B.; Kuo, Chay T.; Wadiche, Jacques I.; Overstreet-Wadiche, Linda

doi:10.1038/ncomms11313

Cited by 92 publications

(108 citation statements)

References 59 publications

(140 reference statements)

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“…Although very young hippocampal neurons fire less specifically and with a reduced latency than older neurons [Schmidt-Hieber et al, 2004;Marin-Burgin et al, 2012;Danielson et al, 2016], perhaps there is an intermediate age during which new, but mature, neurons are better able to achieve the precise firing accuracy necessary for ultrasparse coding compared with aging neurons. Alternatively, or in addition, perhaps young neurons in HVC maintain sparse coding, despite high intrinsic excitability, by balancing broad responsivity with low network connectivity as demonstrated recently in the hippocampus [Dieni et al, 2016]. Therefore, birds with greater numbers of new HVC-RA neurons are better able to maintain the precision necessary for song stereotypy.…”

Section: New Neurons In the Song Motor Pathway Hvc: A Role For New Nementioning

confidence: 94%

“…It may be that the role of new neurons in this region with respect to plasticity and stability is biphasic. The heightened plasticity and low response latency of immature neurons [Schmidt-Hieber et al, 2004;Marin-Burgin et al, 2012] coupled with sparse coding [Dieni et al, 2016] may be characteristics best suited for encoding new memories. Once incorporated into the memory trace, the activity of mature new neurons may serve to stabilize the memory trace.…”

Section: New Neurons In the Hippocampus May Subserve Both Plasticity mentioning

confidence: 99%

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Adult Neurogenesis in the Songbird: Region-Specific Contributions of New Neurons to Behavioral Plasticity and Stability

Pytte

2016

Brain Behav Evol

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Our understanding of the role of new neurons in learning and encoding new information has been largely based on studies of new neurons in the mammalian dentate gyrus and olfactory bulb - brain regions that may be specialized for learning. Thus the role of new neurons in regions that serve other functions has yet to be fully explored. The song system provides a model for studying new neuron function in brain regions that contribute differently to song learning, song auditory discrimination, and song motor production. These regions subserve learning as well as long-term storage of previously learned information. This review examines the differences between learning-based and activity-based retention of new neurons and explores the potential contributions of new neurons to behavioral stability in the song motor production pathway.

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Section: New Neurons In the Song Motor Pathway Hvc: A Role For New Nementioning

confidence: 94%

Section: New Neurons In the Hippocampus May Subserve Both Plasticity mentioning

confidence: 99%

Adult Neurogenesis in the Songbird: Region-Specific Contributions of New Neurons to Behavioral Plasticity and Stability

Pytte

2016

Brain Behav Evol

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“…These data are in keeping with previous observations showing a sparse recruitment of DGCs during a spatial behavioral experience (Chawla et al, 2005). Remarkably, we showed that, in our experimental conditions, activated DGCs display features of mDGCs since (i) the examination of their radial distribution across the cell layer revealed a majority of fosGFP + cells located near the molecular layer, (ii) we did not observe cells that were co-labelled with EGFP and DCX antibodies, and (iii) they exhibited a mean value of Rin characteristic of mature DGCs (Overstreet-Wadiche and Westbrook, 2006; Dieni et al, 2016; Save et al, 2019). These observations reinforce the notion that mDGCs are not dormant cells (Alme et al, 2010) but comprise active neurons involved in specific tasks (Nakashiba et al, 2012; Vukovic et al, 2013).…”

Section: Discussionmentioning

confidence: 59%

Mature dentate granule cells show different intrinsic properties depending on the behavioral context of their activation

Peret

Pléau

Pearlstein

et al. 2018

Preprint

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1The dentate gyrus (DG) plays a crucial role in learning, memory and spatial navigation. Only a 2 small fraction of mature dentate granule cells (mDGCs) is active during behavior, while the 3 large majority remains silent. To date, the properties of this active subset of neurons remain 4 61 5 throughout the experiment (see Materials and Methods), received a water reward at the end of 62 the track after successfully traversing the full track length. After receiving a reward at the first 63 reward zone, the mice then turned around for running in the opposite direction to receive the 64 next reward at the end of the track. In the first sessions (up to 8), the mice moved slowly and 65 erratically along the track as they learned the task. By 8-10 sessions, the mice moved 66 consistently back and forth along the track, and they received rewards at increasing rates over 67 time (1.14 ± 0.05 reward/min, n = 8 mice), they ran reliably back and forth along the track, and 68 they slowed down before reaching the track end consistent with learning of the task (Figure 69 1C). 70To analyse the fraction of DGCs activated in the different behavioral contexts (see above), we 71 used a strain of transgenic mice in which the synthesis of fosGFP fusion protein is controlled 72 by the promoter of the activity-dependent immediate early gene (IEG) c-fos (see Materials and 73 Methods). These mice enabled an ex vivo characterization of activated cells with a recent history 74 of elevated activity in vivo (Barth et al., 2004; Yassin et al., 2010) . In VR training conditions, 75 examination of cells expressing fosGFP was performed ex vivo in hippocampal slices obtained 76 shortly after the last training session (about 18-20 sessions, see Materials and Methods).77Quantification of cells expressing fosGFP was performed in the dorsal hippocampus, which is 78 known to play a crucial role in spatial memory (Moser et al., 1993). When mice were 79 maintained in their home cage, a discreet fraction of DGCs (Prox1-positive, Figure 2C) was 80 activated, since they expressed fosGFP (fosGFP + cells) (1.06 ± 0.1% of DGCs, n = 25 slices, n 81 = 6 mice) (see Figure 1D,E, Materials and Methods) . In line with previous observations (Liu 82 et al., 2012; Kirschen et al., 2017; Shevtsova et al., 2017; Stefanelli et al., 2016), we observed 83 a significant higher fraction of fosGFP + cells in the dorsal hippocampus in mice trained in VR 84(1.92 ± 0.16% of DGCs, n = 19 slices, n = 5 mice, p< 0.0001) ( Figure 1D, E). 85 6 We then explored the distribution of fosGFP + cells across the DG in dorsal hippocampus in the 86 different experimental conditions. To address this question, we plotted the localization of 87 fosGFP + cells in DG and investigated their lateral and radial distributions. DG cell layer extends 88 laterally from the upper (suprapyramidal) blade to the lower (infrapyramidal) blade and from 89 the outer layer (near the molecular layer) to the inner layer (near the hilus) in a radial direction 90 (Altman and Bayer , 1990). In order to reliably...

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“…In line with this hypothesis, Dieni et al showed that low excitatory innervation balanced high excitability of immature neurons in the dentate gyrus and prevented broad responsiveness of these neurons. 24 Although this hypothesis cannot be ruled out, according to our data, the number of GABAergic synapses increased as much as the number of dendritic spines in NL2A-overexpressing post-natal-born neurons, suggesting that the inhibitory/ excitatory balance is maintained in these neurons. As NL1B overexpression in post-natal-born neurons selectively increased excitatory synapse density, assessing the effect of NL1B overexpression in post-natal-born neurons on learning and memory performances would give insight on whether keeping a proper excitation/inhibition balance is crucial for maintaining the proper function of the neuronal network.…”

Section: Introductionmentioning

confidence: 66%

Forced neuronal interactions cause poor communication

Krzisch

Toni

2017

Neurogenesis

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Post-natal hippocampal neurogenesis plays a role in hippocampal function, and neurons born postnatally participate to spatial memory and mood control. However, a great proportion of granule neurons generated in the post-natal hippocampus are eliminated during the first 3 weeks of their maturation, a mechanism that depends on their synaptic integration. In a recent study, we examined the possibility of enhancing the synaptic integration of neurons born post-natally, by specifically overexpressing synaptic cell adhesion molecules in these cells. Synaptic cell adhesion molecules are transmembrane proteins mediating the physical connection between pre-and postsynaptic neurons at the synapse, and their overexpression enhances synapse formation. Accordingly, we found that overexpressing synaptic adhesion molecules increased the synaptic integration and survival of newborn neurons. Surprisingly, the synaptic adhesion molecule with the strongest effect on new neurons' survival, Neuroligin-2A, decreased memory performances in a water maze task. We present here hypotheses explaining these surprising results, in the light of the current knowledge of the mechanisms of synaptic integration of new neurons in the post-natal hippocampus.KEYWORDS post-natal neurogenesis; synaptic adhesion molecule; synaptic partner; synaptogenesis An increasing number of studies indicate that neurons generated in the post-natal hippocampus participate to mechanisms of learning and memory, but also mood control. Indeed, new neurons display increased plastic properties 1 and the role of new neurons in the formation of memory traces was confirmed by optogenetic silencing in mice undergoing a Morris water maze test, which resulted in impaired hippocampal memory retrieval. 2 Similarly, inhibiting post-natal neurogenesis reduces the behavioral effects of antidepressant treatments. 3 It is thought that the functional role of neurons born post-natally critically depends on the mechanisms by which they integrate into the mature hippocampal network, which are still poorly-known. 4 By integrating into the mature network, new neurons preferentially contact pre-existing pre-and postsynaptic partners, which are already involved in synaptic contacts with other neurons. Furthermore, previous work suggests that, upon maturation, new neurons eventually displace or eliminate the pre-existing partners from the synapses they contact, suggesting that a competition at the synaptic level may occur between new and preexisting neurons. 5,6 Further substantiating the possibility of competition, the elimination of NMDA receptors from neurons born post-natally decreases their survival, which can be partially restored upon the pharmacological silencing of NMDA receptors of all hippocampal neurons. 7 Together, these results indicate that neurons born post-natally may compete with pre-existing neurons, eventually resulting in the integration or elimination of new neurons. 8 This competition mechanism may underlie the elimination of a great proportion of postnatal-born ...

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Low excitatory innervation balances high intrinsic excitability of immature dentate neurons

Cited by 92 publications

References 59 publications

Adult Neurogenesis in the Songbird: Region-Specific Contributions of New Neurons to Behavioral Plasticity and Stability

Adult Neurogenesis in the Songbird: Region-Specific Contributions of New Neurons to Behavioral Plasticity and Stability

Mature dentate granule cells show different intrinsic properties depending on the behavioral context of their activation

Forced neuronal interactions cause poor communication

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