The computational influence of neurogenesis in the processing of spatial information in the dentate gyrus.
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ABSTRACT:
SUBMITTER: Cuneo JI
PROVIDER: S-EPMC3471095 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Neurons are born and become a functional part of the synaptic circuitry in adult brains. The proliferative phase of neurogenesis has been extensively reviewed. We therefore focus this review on a few topics addressing the functional role of adult-generated newborn neurons in the dentate gyrus. We discuss the evidence for a link between neurogenesis and behavior. We then describe the steps in the integration of newborn neurons into a functioning mature synaptic circuit. Given the profound effects of neural activity on the differentiation and integration of newborn neurons, we discuss the role of activity-dependent gene expression in the birth and maturation of newborn neurons. The differentiation and maturation of newborn neurons likely involves the concerted action of many genes. Thus we focus on transcription factors that can direct large changes to the transcriptome, and microRNAs, a newly-discovered class of molecules that can effect the expression of hundreds of genes. How microRNAs affect the generation and integration of newborn neurons is just being explored, but there are compelling clues hinting at their involvement.
| S-EPMC3153561 | biostudies-literature
Project description:In adult dentate gyrus neurogenesis, the link between maturation of newborn neurons and their function, such as behavioral pattern separation, has remained puzzling. By analyzing a theoretical model, we show that the switch from excitation to inhibition of the GABAergic input onto maturing newborn cells is crucial for their proper functional integration. When the GABAergic input is excitatory, cooperativity drives the growth of synapses such that newborn cells become sensitive to stimuli similar to those that activate mature cells. When GABAergic input switches to inhibitory, competition pushes the configuration of synapses onto newborn cells toward stimuli that are different from previously stored ones. This enables the maturing newborn cells to code for concepts that are novel, yet similar to familiar ones. Our theory of newborn cell maturation explains both how adult-born dentate granule cells integrate into the preexisting network and why they promote separation of similar but not distinct patterns.
| S-EPMC8260225 | biostudies-literature
Project description:Newborn dentate granule cells (DGCs) are continuously generated in the adult brain. The mechanism underlying how the adult brain governs hippocampal neurogenesis remains poorly understood. In this study, we investigated how coupling of pre-existing neurons to the cerebrovascular system regulates hippocampal neurogenesis. Using a new in vivo imaging method in freely moving mice, we found that hippocampus-engaged behaviors, such as exploration in a novel environment, rapidly increased microvascular blood-flow velocity in the dentate gyrus. Importantly, blocking this exploration-elevated blood flow dampened experience-induced hippocampal neurogenesis. By imaging the neurovascular niche in combination with chemogenetic manipulation, we revealed that pre-existing DGCs actively regulated microvascular blood flow. This neurovascular coupling was linked by parvalbumin-expressing interneurons, primarily through nitric-oxide signaling. Further, we showed that insulin growth factor 1 signaling participated in functional hyperemia-induced neurogenesis. Together, our findings revealed a neurovascular coupling network that regulates experience-induced neurogenesis in the adult brain.
| S-EPMC6728189 | biostudies-literature
Project description:Adult neurogenesis in the dentate gyrus of the hippocampus is highly regulated by environmental influences, and functionally implicated in behavioural responses to stress and antidepressants1-4. However, how adult-born neurons regulate dentate gyrus information processing to protect from stress-induced anxiety-like behaviour is unknown. Here we show in mice that neurogenesis confers resilience to chronic stress by inhibiting the activity of mature granule cells in the ventral dentate gyrus (vDG), a subregion that is implicated in mood regulation. We found that chemogenetic inhibition of adult-born neurons in the vDG promotes susceptibility to social defeat stress, whereas increasing neurogenesis confers resilience to chronic stress. By using in vivo calcium imaging to record neuronal activity from large cell populations in the vDG, we show that increased neurogenesis results in a decrease in the activity of stress-responsive cells that are active preferentially during attacks or while mice explore anxiogenic environments. These effects on dentate gyrus activity are necessary and sufficient for stress resilience, as direct silencing of the vDG confers resilience whereas excitation promotes susceptibility. Our results suggest that the activity of the vDG may be a key factor in determining individual levels of vulnerability to stress and related psychiatric disorders.
| S-EPMC6118212 | biostudies-literature
Project description:Understanding the mechanisms that control the maintenance of neural stem cells is crucial for the study of neurogenesis. In the brain, granule cell neurogenesis occurs during development and adulthood, and the generation of new neurons in the adult subgranular zone of the dentate gyrus contributes to learning. Notch signaling plays an important role during postnatal and adult subgranular zone neurogenesis, and it has been suggested as a potential candidate to couple cell proliferation with stem cell maintenance. Here we show that conditional inactivation of Jagged1 affects neural stem cell maintenance and proliferation during postnatal and adult neurogenesis of the subgranular zone. As a result, granule cell production is severely impaired. Our results provide additional support to the proposal that Notch/Jagged1 activity is required for neural stem cell maintenance during granule cell neurogenesis and suggest a link between maintenance and proliferation of these cells during the early stages of neurogenesis.
| S-EPMC4009513 | biostudies-literature
Project description:Retinoic acid (RA) is commonly used in vitro to differentiate stem cell populations including adult neural stem cells into neurons; however, the in vivo function of RA during adult neurogenesis remains largely unexplored. We found that depletion of RA in adult mice leads to significantly decreased neuronal differentiation within the granular cell layer of the dentate gyrus. RA contribution to neurogenesis occurs early, for RA deficiency also results in a decrease in newborn cells expressing an immature neuronal marker. Furthermore, although proliferation is unaffected during RA absence, cell survival is significantly reduced. Finally, a screen for retinoid-induced genes identifies metabolic targets including the lipid transporters, CD-36 and ABCA-1, the lipogenic master regulator SREBP1c as well as components of the Wnt signaling pathway. Our results reveal RA as a crucial contributor to early stages of adult neurogenesis and survival in vivo.
| S-EPMC1450163 | biostudies-literature
Project description:With continued debate over the functional significance of adult neurogenesis, identifying an in vivo correlate of neurogenesis has become an important goal. Here we rely on the coupling between neurogenesis and angiogenesis and test whether MRI measurements of cerebral blood volume (CBV) provide an imaging correlate of neurogenesis. First, we used an MRI approach to generate CBV maps over time in the hippocampal formation of exercising mice. Among all hippocampal subregions, exercise was found to have a primary effect on dentate gyrus CBV, the only subregion that supports adult neurogenesis. Moreover, exercise-induced increases in dentate gyrus CBV were found to correlate with postmortem measurements of neurogenesis. Second, using similar MRI technologies, we generated CBV maps over time in the hippocampal formation of exercising humans. As in mice, exercise was found to have a primary effect on dentate gyrus CBV, and the CBV changes were found to selectively correlate with cardiopulmonary and cognitive function. Taken together, these findings show that dentate gyrus CBV provides an imaging correlate of exercise-induced neurogenesis and that exercise differentially targets the dentate gyrus, a hippocampal subregion important for memory and implicated in cognitive aging.
| S-EPMC1838482 | biostudies-literature
Project description:Mammalian brains respond to new concepts via a type of neural coding termed "concept coding." During concept coding, the dentate gyrus (DG) plays a vital role in pattern separation and pattern integration of concepts because it is a brain region with substantial neurogenesis in adult mammals. Although concept coding properties of the brain have been extensively studied by experimental work, modeling of the process to guide both further experimental studies and applications such as natural language processing is scarce. To model brain-like concept coding, we built a spiking neural network inspired by adulthood neurogenesis in the DG. Our model suggests that neurogenesis may facilitate integration of closely related concepts and separation of less relevant concepts. Such pattern agrees with the previous experimental observations in classification tasks and place cells in the hippocampus. Therefore, our simulation provides insight for future experimental studies on the neural coding difference between perception and cognition. By presenting 14 contexts each containing 4 concepts to the network, we found that neural responses of the DG changed dynamically as the context repetition time increased and were eventually consistent with the category organization of humans. Thus, our work provides a new framework of word representation for the construction of brain-like knowledge map.
| S-EPMC6877936 | biostudies-literature
Project description:BackgroundAdult neurogenesis continuously adds new neurons to the dentate gyrus and the olfactory bulb. It involves the proliferation and subsequent differentiation of neuronal progenitors, and is thus closely linked to the cell cycle machinery. Cell cycle progression is governed by the successive expression, activation and degradation of regulatory proteins. Among them, D-type cyclins control the exit from the G1 phase of the cell cycle. Cyclin D2 (cD2) has been shown to be required for the generation of new neurons in the neurogenic niches of the adult brain. It is differentially expressed during hippocampal development, and adult cD2 knock out (cD2KO) mice virtually lack neurogenesis in the dentate gyrus and olfactory bulb. In the present study we examined the dynamics of postnatal and adult neurogenesis in the dentate gyrus (DG) of cD2KO mice. Animals were injected with bromodeoxyuridine at seven time points during the first 10 months of life and brains were immunohistochemically analyzed for their potential to generate new neurons.ResultsCompared to their WT litters, cD2KO mice had considerably reduced numbers of newly born granule cells during the postnatal period, with neurogenesis becoming virtually absent around postnatal day 28. This was paralleled by a reduction in granule cell numbers, in the volume of the granule cell layer as well as in apoptotic cell death. CD2KO mice did not show any of the age-related changes in neurogenesis and granule cell numbers that were seen in WT litters.ConclusionsThe present study suggests that hippocampal neurogenesis becomes increasingly dependent on cD2 during early postnatal development. In cD2KO mice, hippocampal neurogenesis ceases at a time point at which the tertiary germinative matrix stops proliferating, indicating that cD2 becomes an essential requirement for ongoing neurogenesis with the transition from developmental to adult neurogenesis. Our data further support the notion that adult neurogenesis continuously adds new neurons to the hippocampal network, hence increasing cell density of the DG.
| S-EPMC3403990 | biostudies-literature
Project description:An approach combining signal detection theory and precise 3D reconstructions from serial section electron microscopy (3DEM) was used to investigate synaptic plasticity and information storage capacity at medial perforant path synapses in adult hippocampal dentate gyrus in vivo. Induction of long-term potentiation (LTP) markedly increased the frequencies of both small and large spines measured 30 minutes later. This bidirectional expansion resulted in heterosynaptic counterbalancing of total synaptic area per unit length of granule cell dendrite. Control hemispheres exhibited 6.5 distinct spine sizes for 2.7 bits of storage capacity while LTP resulted in 12.9 distinct spine sizes (3.7 bits). In contrast, control hippocampal CA1 synapses exhibited 4.7 bits with much greater synaptic precision than either control or potentiated dentate gyrus synapses. Thus, synaptic plasticity altered total capacity, yet hippocampal subregions differed dramatically in their synaptic information storage capacity, reflecting their diverse functions and activation histories.
| S-EPMC5877922 | biostudies-literature