In vivo imaging of dendritic pruning in dentate granule cells

Gonçalves, J. Tiago; Bloyd, Cooper W; Shtrahman, Matthew; Johnston, Stephen T.; Schäfer, Simon; Parylak, Sarah; Tran, Thanh; Chang, Tina; Gage, Fred H.

doi:10.1038/nn.4301

Cited by 85 publications

(77 citation statements)

References 23 publications

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“…Granular cell morphology is well‐characterized (Ampuero et al, ; Jain et al, ; Zhao, Teng, Summers, Ming, & Gage, ) with localization of the cell body in the supragranular layer and dendritic branch projections toward the molecular layers (Figure A and B). Under control conditions, the GFP‐positive granular cells displayed a dendritic arbor with several secondary processes emerging from the primary dendritic process, as previously described (Ampuero et al, ; Gonçalves et al, ; Zhao et al, ). Interestingly, adult granular neurons transducing NR2AΔIN displayed a more complex dendritic arbor (Figure B) with significantly increased total dendritic length (Figure C) relative to control neurons.…”

Section: Resultssupporting

confidence: 73%

NMDA receptor subunit composition controls dendritogenesis of hippocampal neurons through CAMKII, CREB‐P, and H3K27ac

Bustos

Jury

Martínez

et al. 2017

Journal Cellular Physiology

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Dendrite arbor growth, or dendritogenesis, is choreographed by a diverse set of cues, including the NMDA receptor (NMDAR) subunits NR2A and NR2B. While NR1NR2B receptors are predominantly expressed in immature neurons and promote plasticity, NR1NR2A receptors are mainly expressed in mature neurons and induce circuit stability. How the different subunits regulate these processes is unclear, but this is likely related to the presence of their distinct C-terminal sequences that couple different signaling proteins. Calcium-calmodulin-dependent protein kinase II (CaMKII) is an interesting candidate as this protein can be activated by calcium influx through NMDARs. CaMKII triggers a series of biochemical signaling cascades, involving the phosphorylation of diverse targets. Among them, the activation of cAMP response element-binding protein (CREB-P) pathway triggers a plasticity-specific transcriptional program through unknown epigenetic mechanisms. Here, we found that dendritogenesis in hippocampal neurons is impaired by several well-characterized constructs (i.e., NR2B-RS/QD) and peptides (i.e., tatCN21) that specifically interfere with the recruitment and interaction of CaMKII with the NR2B C-terminal domain. Interestingly, we found that transduction of NR2AΔIN, a mutant NR2A construct with increased interaction to CaMKII, reactivates dendritogenesis in mature hippocampal neurons in vitro and in vivo. To gain insights into the signaling and epigenetic mechanisms underlying NMDAR-mediated dendritogenesis, we used immunofluorescence staining to detect CREB-P and acetylated lysine 27 of histone H3 (H3K27ac), an activation-associated histone tail mark. In contrast to control mature neurons, our data shows that activation of the NMDAR/CaMKII/ERK-P/CREB-P signaling axis in neurons expressing NR2AΔIN is not correlated with increased nuclear H3K27ac levels.

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Section: Resultssupporting

confidence: 73%

NMDA receptor subunit composition controls dendritogenesis of hippocampal neurons through CAMKII, CREB‐P, and H3K27ac

Bustos

Jury

Martínez

et al. 2017

Journal Cellular Physiology

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“…Thereafter, the dendritic structure remained stable up to 60 dpi. These results suggest a stereotypical sequence driving GC morphological changes to maturity, similar to that observed in adult-born neurons in the hippocampus in vivo and with serial reconstruction imaging (Gonçalves et al, 2016; Sun et al, 2013). Synaptic inputs to the GC basal dendrites, primarily from top-down centrifugal fibers and MC/TC collaterals, become active at 10 dpi, and this activity may drive the maturation steps (Kelsch et al, 2008; Whitman and Greer, 2007).…”

Section: Discussionsupporting

confidence: 68%

Persistent Structural Plasticity Optimizes Sensory Information Processing in the Olfactory Bulb

Sailor

Valley

Wiechert

et al. 2016

Neuron

111

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SUMMARY In the mammalian brain, the anatomical structure of neural circuits changes little during adulthood. As a result, adult learning and memory are thought to result from specific changes in synaptic strength. A possible exception is the olfactory bulb (OB), where activity guides interneuron turnover throughout adulthood. These adult-born granule cell (GC) interneurons form new GABAergic synapses that have little synaptic strength plasticity. In the face of persistent neuronal and synaptic turnover, how does the OB balance flexibility, as is required for adapting to changing sensory environments, with perceptual stability? Here we show that high dendritic spine turnover is a universal feature of GCs, regardless of their developmental origin and age. We find matching dynamics among postsynaptic sites on the principal neurons receiving the new synaptic inputs. We further demonstrate in silico that this coordinated structural plasticity is consistent with stable, yet flexible, decorrelated sensory representations. Together, our study reveals that persistent, coordinated synaptic structural plasticity between interneurons and principal neurons is a major mode of functional plasticity in the OB.

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“…In their preparations, an apically extending dendrite was observed, but the long-term fate of this dendrite could not be ascertained. In recently published work by Gonçalves and colleagues (2016), the dendritic dynamics of GCs born in the adult mouse brain were described using 2-photon imaging55. These authors showed growth and pruning of adult born GC dendrites in vivo , similar to what we report here for the OTC preparation.…”

Section: Discussionsupporting

confidence: 83%

“…local, dendritic reorganization occurring. The overall morphology and dynamics of these 3–4-week-old RV-labeled cells in our rat OTCs was found to be well comparable to cells in the adult mouse DG in vivo 55. Thus, we here report a highly dynamic integration of GCs into their termination zone which is characterized by both, dendritic growth as well as dendritic retraction.…”

Section: Discussionsupporting

confidence: 73%

Time-lapse imaging reveals highly dynamic structural maturation of postnatally born dentate granule cells in organotypic entorhino-hippocampal slice cultures

Radic

Jungenitz

Singer

et al. 2017

Sci Rep

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Neurogenesis of hippocampal granule cells (GCs) persists throughout mammalian life and is important for learning and memory. How newborn GCs differentiate and mature into an existing circuit during this time period is not yet fully understood. We established a method to visualize postnatally generated GCs in organotypic entorhino-hippocampal slice cultures (OTCs) using retroviral (RV) GFP-labeling and performed time-lapse imaging to study their morphological development in vitro. Using anterograde tracing we could, furthermore, demonstrate that the postnatally generated GCs in OTCs, similar to adult born GCs, grow into an existing entorhino-dentate circuitry. RV-labeled GCs were identified and individual cells were followed for up to four weeks post injection. Postnatally born GCs exhibited highly dynamic structural changes, including dendritic growth spurts but also retraction of dendrites and phases of dendritic stabilization. In contrast, older, presumably prenatally born GCs labeled with an adeno-associated virus (AAV), were far less dynamic. We propose that the high degree of structural flexibility seen in our preparations is necessary for the integration of newborn granule cells into an already existing neuronal circuit of the dentate gyrus in which they have to compete for entorhinal input with cells generated and integrated earlier.

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In vivo imaging of dendritic pruning in dentate granule cells

Cited by 85 publications

References 23 publications

NMDA receptor subunit composition controls dendritogenesis of hippocampal neurons through CAMKII, CREB‐P, and H3K27ac

NMDA receptor subunit composition controls dendritogenesis of hippocampal neurons through CAMKII, CREB‐P, and H3K27ac

Persistent Structural Plasticity Optimizes Sensory Information Processing in the Olfactory Bulb

Time-lapse imaging reveals highly dynamic structural maturation of postnatally born dentate granule cells in organotypic entorhino-hippocampal slice cultures

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