Watching Synaptogenesis in the Adult Brain

Kelsch, Wolfgang; Sim, Shuyin; Lois, Carlos

doi:10.1146/annurev-neuro-060909-153252

Cited by 82 publications

(65 citation statements)

References 93 publications

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“…The drill-andpractice method is based on the principle of experiencedependent neuroplasticity demonstrated in animal models and a systems approach to understanding cognitive dysfunction; changes in cognitive functioning may arise from repeated practice and the consequent strengthening of neural networks underlying basic and more complex cognitive processes. 17 Improvement in a range of cognitive abilities is thought to facilitate the acquisition of relevant functional skills. Strategy-based approaches focus on learning techniques for circumventing cognitive difficulties.…”

Section: Key Influences On the Emergence Of Cr For Schizophreniamentioning

confidence: 99%

“…17 In people with schizophrenia, there are data showing an association between CR and a reduction in characteristic loss of and, in some cases, increase in brain grey matter volume, associated with improved cognition. 26,27 Changes in measures of neural activity and volume in brain areas that support social cognition have been demonstrated as well.…”

Section: Trends In Restorative Cognitive Trainingmentioning

confidence: 99%

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Current Trends in the Empirical Study of Cognitive Remediation for Schizophrenia

Saperstein

Kurtz

2013

Can J Psychiatry

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Cognitive remediation (CR) for schizophrenia is a learning-based behavioural skills training intervention designed to enhance neuro and (or) social cognitive skills, with the ultimate goal of generalization to improve psychosocial outcomes. This review summarizes conceptual approaches to CR for schizophrenia and the evidence for efficacy in clinical research settings. Four issues are at the forefront of ongoing research: the identification of techniques that produce the largest cognitive change, delineation of techniques that enhance transfer of cognitive skills to functional skills, the identification of CR methods that can be personalized to meet the specific cognitive and functional needs of each individual, and, all the while, ensuring that when CR methods are developed in a research setting, they remain scalable for delivery in the larger clinical community. In response to these issues, 3 prominent research trends have emerged: the rise of a new generation of computerized restorative cognitive training, the integration of CR with skills training to promote generalization, and the application of techniques to enhance motivation and learning during CR. As data on the neural basis of learning in people with schizophrenia become available, new technologies that harness the ability of the brain to make sustainable, functional changes may be integrated within a therapeutic context that promotes a personalized approach to learning. The development of transportable and scalable methods of CR that maximize the ability of people with schizophrenia to improve cognition will help them achieve personal goals for recovery. W W WTendances actuelles de l'étude empirique de la rééducation cognitive pour la schizophrénie La rééducation cognitive (RC) pour la schizophrénie est une intervention de formation comportementale par l'apprentissage, destinée à améliorer les aptitudes cognitives neuro et (ou) sociales, dans un but final de généralisation afin d'améliorer les résultats psychosociaux. Cette étude résume les approches conceptuelles de la RC pour la schizophrénie et les données probantes d'efficacité dans des contextes de recherche clinique. Quatre questions sont à l'avant-plan de la recherche en cours : l'identification des techniques qui produisent le plus grand changement cognitif, la délimitation des techniques qui améliorent le transfert des aptitudes cognitive s aux aptitudes fonctionnelles, l'identification des méthodes de RC qui peuvent être personnalisées pour répondre aux besoins cognitifs et fonctionnels spécifiques de chaque personne, et, pendant ce temps, faire en sorte que les méthodes de la RC soient développées dans un cadre de recherche, qu'elles demeurent évolutives et applicables à la grande communauté clinique. En réponse à ces questions, 3 tendances proéminentes de la recherche se sont dessinées : la montée d'une nouvelle génération de formation cognitive restauratrice informatisée, l'intégration de la RC avec la formation axée sur les aptitudes pour promouvoir la généralisation, et l'application de ...

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Section: Key Influences On the Emergence Of Cr For Schizophreniamentioning

confidence: 99%

Section: Trends In Restorative Cognitive Trainingmentioning

confidence: 99%

Current Trends in the Empirical Study of Cognitive Remediation for Schizophrenia

Saperstein

Kurtz

2013

Can J Psychiatry

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“…GCs are generated in the subventricular zone (SVZ) and integrate both into the developing (neonatal) and adult OB (Lois and Alvarez-Buylla, 1994). They are axon-less interneurons with an apical and a basal dendrite (Mori, 1987;Kelsch et al, 2010). The apical dendrite contains two domains (Fig.…”

Section: Introductionmentioning

confidence: 99%

Postnatal subventricular zone progenitors switch their fate to generate neurons with distinct synaptic input patterns

Ravi

Oettl

et al. 2015

Development

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New granule cell neurons (GCs) generated in the neonatal and adult subventricular zone (SVZ) have distinct patterns of input synapses in their dendritic domains. These synaptic input patterns determine the computations that the neurons eventually perform in the olfactory bulb. We observed that GCs generated earlier in postnatal life had acquired an 'adult' synaptic development only in one dendritic domain, and only later-born GCs showed an 'adult' synaptic development in both dendritic domains. It is unknown to what extent the distinct synaptic input patterns are already determined in SVZ progenitors and/or by the brain circuit into which neurons integrate. To distinguish these possibilities, we heterochronically transplanted retrovirally labeled SVZ progenitor cells. Once these transplanted progenitors, which mainly expressed Mash1, had differentiated into GCs, their glutamatergic input synapses were visualized by genetic tags. We observed that GCs derived from neonatal progenitors differentiating in the adult maintained their characteristic neonatal synapse densities. Grafting of adult SVZ progenitors to the neonate had a different outcome. These GCs formed synaptic densities that corresponded to neither adult nor neonatal patterns in two dendritic domains. In summary, progenitors in the neonatal and adult brain generate distinct GC populations and switch their fate to generate neurons with specific synaptic input patterns. Once they switch, adult progenitors require specific properties of the circuit to maintain their characteristic synaptic input patterns. Such determination of synaptic input patterns already at the progenitor-cell level may be exploited for brain repair to engineer neurons with defined wiring patterns.

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“…Importantly, the impact of this process depends on the overall synaptic activity of the preexisting circuit (Kelsch et al, 2010;Ming and Song, 2011). As a result, some of the most important parameters regulating adult neurogenesis are guided by the properties of the early synapses impinging onto developing adult-born neurons.…”

Section: Introductionmentioning

confidence: 99%

Early Formation of GABAergic Synapses Governs the Development of Adult-Born Neurons in the Olfactory Bulb

Pallotto

Nissant²,

Fritschy

et al. 2012

Journal of Neuroscience

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In mammals, olfactory bulb granule cells (GCs) are generated throughout life in the subventricular zone. GABAergic inputs onto newborn neurons likely regulate their maturation, but the details of this process remain still elusive. Here, we investigated the differentiation, synaptic integration, and survival of adult-born GCs when their afferent GABAergic inputs are challenged by conditional gene targeting. Migrating GC precursors were targeted with Cre-eGFP-expressing lentiviral vectors in mice with a floxed gene encoding the GABA A receptor ␣2-subunit (i.e., Gabra2). Ablation of the ␣2-subunit did not affect GC survival but dramatically delayed their maturation. We found a reduction in postsynaptic ␣2-subunit and gephyrin clusters accompanied by a decrease in the frequency and amplitude of GABAergic postsynaptic currents beginning ϳ14 d post-injection (dpi). In addition, mutant cells exhibited altered dendritic branching and spine density. Spine loss appeared with mislocation of glutamatergic synapses on dendritic shafts and a reduction of spontaneous glutamatergic postsynaptic currents, underscoring the relevance of afferent GABAergic transmission for a proper synaptic integration of newborn GCs. To test the role of GABAergic signaling during much early stages of GC maturation, we used a genetic strategy to selectively inactivate Gabra2 in precursor cells of the subventricular zone. In these mice, labeling of newborn GCs with eGFP lentiviruses revealed similar morphological alterations as seen on delayed Gabra2 inactivation in migrating neuroblasts, with reduced dendritic branching and spine density at 7 dpi. Collectively, these results emphasize the critical role of GABAergic synaptic signaling for structural maturation of adult-born GCs and formation of glutamatergic synapses.

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Watching Synaptogenesis in the Adult Brain

Cited by 82 publications

References 93 publications

Current Trends in the Empirical Study of Cognitive Remediation for Schizophrenia

Current Trends in the Empirical Study of Cognitive Remediation for Schizophrenia

Postnatal subventricular zone progenitors switch their fate to generate neurons with distinct synaptic input patterns

Early Formation of GABAergic Synapses Governs the Development of Adult-Born Neurons in the Olfactory Bulb

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