Structural homo- and heterosynaptic plasticity in mature and adult newborn rat hippocampal granule cells

Jungenitz, Tassilo; Beining, Marcel; Radic, Tijana; Deller, Thomas; Cuntz, Hermann; Jedlicka, Paul; Schwarzacher, Stephan W.

doi:10.1073/pnas.1801889115

Cited by 40 publications

(73 citation statements)

References 56 publications

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“…In the adult hippocampal dentate gyrus a tightly regulated transcription factor sequence that includes SOX11, generates new functional dentate granule neurons 22 – 24 . Adult-generated hippocampal DG neurons feature a highly stereotypic dendritic morphology, which is essential for DG neuron function and whose perturbation is associated with deficits in hippocampus-dependent information processing and behavior 25 – 29 . Having confirmed that SOXC transcription factor function is essential for neuronal differentiation in the adult neurogenic lineage 1 , we found that SOX11 and its S133 phospho-mutants were equally potent in rescuing the neuronal differentiation deficit of SoxC-deficient cells in vivo .…”

Section: Discussionmentioning

confidence: 99%

Phosphorylation of the neurogenic transcription factor SOX11 on serine 133 modulates neuronal morphogenesis

Balta

Schäffner

Wittmann

et al. 2018

Sci Rep

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The intellectual disability gene, Sox11, encodes for a critical neurodevelopmental transcription factor with functions in precursor survival, neuronal fate determination, migration and morphogenesis. The mechanisms regulating SOX11’s activity remain largely unknown. Mass spectrometric analysis uncovered that SOX11 can be post-translationally modified by phosphorylation. Here, we report that phosphorylatable serines surrounding the high-mobility group box modulate SOX11’s transcriptional activity. Through Mass Spectrometry (MS), co-immunoprecipitation assays and in vitro phosphorylation assays followed by MS we verified that protein kinase A (PKA) interacts with SOX11 and phosphorylates it on S133. In vivo replacement of SoxC factors in developing adult-generated hippocampal neurons with SOX11 S133 phospho-mutants indicated that phosphorylation on S133 modulates dendrite development of adult-born dentate granule neurons, while reporter assays suggested that S133 phosphorylation fine-tunes the activation of select target genes. These data provide novel insight into the control of the critical neurodevelopmental regulator SOX11 and imply SOX11 as a mediator of PKA-regulated neuronal development.

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Section: Discussionmentioning

confidence: 99%

Phosphorylation of the neurogenic transcription factor SOX11 on serine 133 modulates neuronal morphogenesis

Balta

Schäffner

Wittmann

et al. 2018

Sci Rep

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“…In introducing local synaptic heterogeneity, we picked ranges for

{\overset{false¯}{P}}_{AMPAR}

and

{\overset{false¯}{P}}_{GABAAR}

that satisfied the firing rate requirements above and picked values for

{\overset{false¯}{P}}_{AMPAR}

and

{\overset{false¯}{P}}_{GABAAR}

(for all synapses in the network) from independent uniform distributions spanning this range (Figure c). Such local synaptic heterogeneities could be consequent to baseline biological variability in presynaptic properties and postsynaptic receptor densities, differential dendritic processing of inputs owing to active and passive filtering, differential spine sizes consequent to the interaction between homo‐ and heterosynaptic spine plasticity and homeostatic regulation of overall synaptic drives (Aimone et al, ; Coulter & Carlson, ; Dieni et al, ; Dieni et al, ; Jedlicka, Benuskova, & Abraham, ; Jungenitz et al, ; Krueppel et al, ; Li et al, ; Mongiat, Esposito, Lombardi, & Schinder, ).…”

Section: Methodsmentioning

confidence: 99%

Disparate forms of heterogeneities and interactions among them drive channel decorrelation in the dentate gyrus: Degeneracy and dominance

2018

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The ability of a neuronal population to effectuate channel decorrelation, which is one form of response decorrelation, has been identified as an essential prelude to efficient neural encoding. To what extent are diverse forms of local and afferent heterogeneities essential in accomplishing channel decorrelation in the dentate gyrus (DG)? Here, we incrementally incorporated four distinct forms of biological heterogeneities into conductance‐based network models of the DG and systematically delineate their relative contributions to channel decorrelation. First, to effectively incorporate intrinsic heterogeneities, we built physiologically validated heterogeneous populations of granule (GC) and basket cells (BC) through independent stochastic search algorithms spanning exhaustive parametric spaces. These stochastic search algorithms, which were independently constrained by experimentally determined ion channels and by neurophysiological signatures, revealed cellular‐scale degeneracy in the DG. Specifically, in GC and BC populations, disparate parametric combinations yielded similar physiological signatures, with underlying parameters exhibiting significant variability and weak pair‐wise correlations. Second, we introduced synaptic heterogeneities through randomization of local synaptic strengths. Third, in including adult neurogenesis, we subjected the valid model populations to randomized structural plasticity and matched neuronal excitability to electrophysiological data. We assessed networks comprising different combinations of these three local heterogeneities with identical or heterogeneous afferent inputs from the entorhinal cortex. We found that the three forms of local heterogeneities were independently and synergistically capable of mediating significant channel decorrelation when the network was driven by identical afferent inputs. However, when we incorporated afferent heterogeneities into the network to account for the divergence in DG afferent connectivity, the impact of all three forms of local heterogeneities was significantly suppressed by the dominant role of afferent heterogeneities in mediating channel decorrelation. Our results unveil a unique convergence of cellular‐ and network‐scale degeneracy in the emergence of channel decorrelation in the DG, whereby disparate forms of local and afferent heterogeneities could synergistically drive input discriminability.

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“…The mechanisms behind the trafficking of several ion channels have been studied (Cusdin, Clare, & Jackson, ; Jensen, Rasmussen, & Misonou, ; Lai & Jan, ; Lau & Zukin, ; Lujan et al, ; Shah et al, ; Vacher et al, ; Wenthold, Prybylowski, Standley, Sans, & Petralia, ), and it is now clear that plasticity is ubiquitous (Kim & Linden, ). In addition to these changes in cytosolic and membrane proteins, it has been shown that hippocampal spines undergo continuous structural changes, apart from demonstrations of distinct forms of structural plasticity in spines, dendrites and axons (Attardo, Fitzgerald, & Schnitzer, ; Chen, Lu, & Zuo, ; Emoto, ; Engert & Bonhoeffer, ; Ghiretti & Paradis, ; Grubb & Burrone, ; Grubb & Burrone, ; Grubb et al, ; Ikegaya et al, ; Johnston et al, ; Jungenitz et al, ; Luo & O'Leary, ; Matsuzaki et al, ; Nagerl et al, ; Tonnesen et al, ; Yuste & Bonhoeffer, ). Finally, the dynamics associated with the various glial functions and their interactions with neuronal and metabolic pathways could also undergo changes in response to behavioral experiences and activity (Araque et al, ; Ashhad & Narayanan, 2019; Baumann & Pham‐Dinh, ; Fields, ; Halassa & Haydon, ; Haydon & Carmignoto, ; Khakh & Sofroniew, ; Pannasch & Rouach, ; Perea et al, ; Sierra, Tremblay, & Wake, ; Volterra, Liaudet, & Savtchouk, ).…”

Section: Degeneracy At Multiple Scales In the Hippocampusmentioning

confidence: 99%

“…The mechanisms behind the trafficking of several ion channels have been studied (Cusdin, Clare, & Jackson, 2008;Jensen, Rasmussen, & Misonou, 2011;Lai & Jan, 2006;Lau & Zukin, 2007;Lujan et al, 2009;Shah et al, 2010;Vacher et al, 2008;Wenthold, Prybylowski, Standley, Sans, & Petralia, 2003), and it is now clear that plasticity is ubiquitous (Kim & Linden, 2007). In addition to these changes in cytosolic and membrane proteins, it has been shown that hippocampal spines undergo continuous structural changes, apart from demonstrations of distinct forms of structural plasticity in spines, dendrites and axons (Attardo, Fitzgerald, & Schnitzer, 2015;Chen, Lu, & Zuo, 2014;Emoto, 2011;Engert & Bonhoeffer, 1999;Ghiretti & Paradis, 2014;Grubb & Burrone, 2010a;Grubb & Burrone, 2010b;Grubb et al, 2011;Ikegaya et al, 2001;Johnston et al, 2016;Jungenitz et al, 2018;Luo & O'Leary, 2005;Matsuzaki et al, 2004;Nagerl et al, 2004;Tonnesen et al, 2014;Yuste & Bonhoeffer, 2001).…”

Section: Degeneracy In the Induction And Expression Of Nonsynaptic mentioning

confidence: 99%

Degeneracy in hippocampal physiology and plasticity

2019

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Degeneracy, defined as the ability of structurally disparate elements to perform analogous function, has largely been assessed from the perspective of maintaining robustness of physiology or plasticity. How does the framework of degeneracy assimilate into an encoding system where the ability to change is an essential ingredient for storing new incoming information? Could degeneracy maintain the balance between the apparently contradictory goals of the need to change for encoding and the need to resist change towards maintaining homeostasis? In this review, we explore these fundamental questions with the mammalian hippocampus as an example encoding system. We systematically catalog lines of evidence, spanning multiple scales of analysis that point to the expression of degeneracy in hippocampal physiology and plasticity. We assess the potential of degeneracy as a framework to achieve the conjoint goals of encoding and homeostasis without cross‐interferences. We postulate that biological complexity, involving interactions among the numerous parameters spanning different scales of analysis, could establish disparate routes towards accomplishing these conjoint goals. These disparate routes then provide several degrees of freedom to the encoding‐homeostasis system in accomplishing its tasks in an input‐ and state‐dependent manner. Finally, the expression of degeneracy spanning multiple scales offers an ideal reconciliation to several outstanding controversies, through the recognition that the seemingly contradictory disparate observations are merely alternate routes that the system might recruit towards accomplishment of its goals.

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Structural homo- and heterosynaptic plasticity in mature and adult newborn rat hippocampal granule cells

Cited by 40 publications

References 56 publications

Phosphorylation of the neurogenic transcription factor SOX11 on serine 133 modulates neuronal morphogenesis

Phosphorylation of the neurogenic transcription factor SOX11 on serine 133 modulates neuronal morphogenesis

Disparate forms of heterogeneities and interactions among them drive channel decorrelation in the dentate gyrus: Degeneracy and dominance

Degeneracy in hippocampal physiology and plasticity

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