Abstract:
The dentate gyrus (DG) of the hippocampus is a mosaic of dentate granule neurons (DGNs) accumulated throughout life. While many studies focused on the morpho-functional properties of adult-born DGNs, much less is known about DGNs generated during development, and in particular those born during embryogenesis. One of the main reasons for this gap is the lack of methods available to specifically label and manipulate embryonically-born DGNs. Here, we have assessed the relevance of the Penk(Cre) mouse line as a genetic model to target this embryonically-born population. In young animals, Penk(Cre) expression allows to tag neurons in the DG with positional, morphological and electrophysiological properties characteristic of DGNs born during the embryonic period. In addition, Penk(Cre)+ cells in the DG are distributed in both blades along the entire septo-temporal axis. This model thus offers new possibilities to explore the functions of this underexplored population of embryonically-born DGNs.

Abstract:
Hippocampal adult neurogenesis is involved in many memory processes from learning, to remembering and forgetting. However, whether or not the stimulation of adult neurogenesis is a sufficient condition to improve memory performance remains unclear. Here, we developed and validated, using ex-vivo electrophysiology, a chemogenetic approach that combines selective tagging and activation of discrete adult-born neuron populations. Then we demonstrated that, in rats, this activation can improve accuracy and strength of remote memory. These results show that stimulation of adult-born neuron activity can counteract the natural fading of memory traces that occurs with the passage of time. This opens up new avenues for treating memory problems that may arise over time.

Abstract:
Despite the central role of Rho GTPases in neuronal development, their functions in adult hippocampal neurogenesis remain poorly explored. Here, by using a retrovirus-based loss-of-function approach in vivo, we show that the atypical Rho GTPase Rnd2 is crucial for survival, positioning, somatodendritic morphogenesis, and functional maturation of adult-born dentate granule neurons. Interestingly, most of these functions are specific to granule neurons generated during adulthood since the deletion of Rnd2 in neonatally-born granule neurons only affects dendritogenesis. In addition, suppression of Rnd2 in adult-born dentate granule neurons increases anxiety-like behavior whereas its deletion in pups has no such effect, a finding supporting the adult neurogenesis hypothesis of anxiety disorders. Thus, our results are in line with the view that adult neurogenesis is not a simple continuation of earlier processes from development, and establish a causal relationship between Rnd2 expression and anxiety.

Abstract:
Memory reconsolidation, the process by which memories are again stabilized after being reactivated, has strengthened the idea that memory stabilization is a highly plastic process. To date, the molecular and cellular bases of reconsolidation have been extensively investigated particularly within the hippocampus. However, the role of adult neurogenesis in memory reconsolidation is unclear. Here, we combined functional imaging, retroviral and chemogenetic approaches in rats to tag and manipulate different populations of rat adult-born neurons. We find that both mature and immature adult-born neurons are activated by remote memory retrieval. However, only specific silencing of the adult-born neurons immature during learning impairs remote memory retrieval-induced reconsolidation. Hence, our findings show that adult-born neurons immature during learning are required for the maintenance and update of remote memory reconsolidation.

Abstract:
Rnd proteins constitute a subfamily of Rho GTPases represented in mammals by Rnd1, Rnd2 and Rnd3. Despite their GTPase structure, their specific feature is the inability to hydrolyse GTP-bound nucleotide. This aspect makes them atypical among Rho GTPases. Rnds are regulated for their expression at the transcriptional or post-transcriptional levels and they are activated through post-translational modifications and interactions with other proteins. Rnd proteins are mainly involved in the regulation of the actin cytoskeleton and cell proliferation. Whereas Rnd3 is ubiquitously expressed, Rnd1 and 2 are tissue-specific. Increasing data has described their important role during development and diseases. Herein, we describe their involvement in physiological and pathological conditions with a focus on the neuronal and vascular systems, and summarize their implications in tumorigenesis.

Abstract:

Abstract:
The calcium/calmodulin-dependent protein kinase II (CaMKII) is a ubiquitous and central player in Ca(2+) signaling that is best known for its functions in the brain. In particular, the ? isoform of CaMKII has been the subject of intense research and it has been established as a central regulator of neuronal plasticity. In contrast, little attention has been paid to CaMKII?, the other predominant brain isoform that interacts directly with the actin cytoskeleton, and the functions of CaMKII? in this organ remain largely unexplored. However, recently, the perturbation of CaMKII? expression has been associated with multiple neuropsychiatric and neurodevelopmental diseases, highlighting CAMK2B as a gene of interest. Herein, after highlighting the main structural and expression differences between the ? and ? isoforms, we will review the specific functions of CaMKII?, as described so far, in neuronal development and plasticity, as well as its potential implication in brain diseases.

Abstract:
Perturbation of CaMKIIbeta expression has been associated with multiple neuropsychiatric diseases, highlighting CaMKIIbeta as a gene of interest. Yet, in contrast to CaMKIIalpha, the specific functions of CaMKIIbeta in the brain remain poorly explored. Here, we reveal a novel function for this CaMKII isoform in vivo during neuronal development. By using in utero electroporation, we show that CaMKIIbeta is an important regulator of radial migration of projection neurons during cerebral cortex development. Knockdown of CaMKIIbeta causes accelerated migration of nascent pyramidal neurons, whereas overexpression of CaMKIIbeta inhibits migration, demonstrating that precise regulation of CaMKIIbeta expression is required for correct neuronal migration. More precisely, CaMKIIbeta controls the multipolar-bipolar transition in the intermediate zone and locomotion in the cortical plate through its actin-binding and -bundling activities. In addition, our data indicate that a fine-tuned balance between CaMKIIbeta and cofilin activities is necessary to ensure proper migration of cortical neurons. Thus, our findings define a novel isoform-specific function for CaMKIIbeta, demonstrating that CaMKIIbeta has a major biological function in the developing brain.

Abstract:

Abstract:
In nonhuman mammals and in particular in rodents, most granule neurons of the dentate gyrus (DG) are generated during development and yet little is known about their properties compared with adult-born neurons. Although it is generally admitted that these populations are morphologically indistinguishable once mature, a detailed analysis of developmentally born neurons is lacking. Here, we used in vivo electroporation to label dentate granule cells (DGCs) generated in mouse embryos (E14.5) or in neonates (P0) and followed their morphological development up to 6 months after birth. By comparison with mature retrovirus-labeled DGCs born at weaning (P21) or young adult (P84) stages, we provide the evidence that perinatally born neurons, especially embryonically born cells, are morphologically distinct from later-born neurons and are thus easily distinguishable. In addition, our data indicate that semilunar and hilar GCs, 2 populations in ectopic location, are generated during the embryonic and the neonatal periods, respectively. Thus, our findings provide new insights into the development of the different populations of GCs in the DG and open new questions regarding their function in the brain.