New Neurons Don’t Talk Back

GABAergic interneurons enforce highly sparse activity patterns in principal neurons of the dentate gyrus. In this issue of Neuron, Temprana et al. (2015) show that immature adult-born neurons largely function independently of inhibitory feedback circuits, neither receiving nor generating feedback inhibition

Hilar Mossy Cells Provide the First Glutamatergic Synapses to Adult-Born Dentate Granule Cells

Adult-generated granule cells (GCs) in the dentate gyrus must establish synapses with preexisting neurons to participate in network activity. To determine the source of early glutamatergic synapses on newborn GCs in adult mice, we examined synaptic currents at the developmental stage when NMDA receptor-mediated silent synapses are first established. We show that hilar mossy cells provide initial glutamatergic synapses as well as disynaptic GABAergic input to adult-generated dentate GCs

Enhanced Integration of Newborn Neurons after Neonatal Insults

The production and integration of adult-generated neurons in the dentate gyrus is dramatically perturbed by a variety of pathological insults, including repetitive seizures and hypoxia/ischemia. Less is known about how insults affect early postnatal neurogenesis, during the developmental period when the majority of dentate neurons are produced. Here we tested how single episodes of hypoxia or chemically induced seizure activity in postnatal day 10 mice alter granule cell production and integration. Although neither insult was sufficient to alter the number of newborn neurons nor the population of proliferating cells, both treatments increased the dendritic complexity of newborn granule cells that were born around the time of the insult. Surprisingly, only the dendritic enhancement caused by hypoxia was associated with increased synaptic integration. These results suggest that alterations in dendritic integration can be dissociated from altered neural production and that integration appears to have a lower threshold for perturbation. Furthermore, newborn neurons in adult mice that experienced neonatal hypoxia had reduced dendritic length while having no alterations in number. Together these results suggest that single insults during the neonatal period can have both long- and short-term consequences for neuronal maturation

Functional maturation of adult-generated granule cells,”Hippocampus

ABSTRACT: The excitability and connectivity of adult-generated granule cells dictate to what extent newborn neurons participate in the hippocampal network. These functional parameters evolve as newborn cells mature and interact with the existing circuit. The progression of granule cell maturation during neonatal development appears to be reiterated in the adult, but with some caveats. New approaches to identify and track newborn neurons are revealing the timing of this process, as well as its sensitivity to activity-dependent regulation. V V C 2006 Wiley-Liss, Inc

Afferent convergence to a shared population of interneuron AMPA receptors

Abstract Precise alignment of pre- and postsynaptic elements optimizes the activation of glutamate receptors at excitatory synapses. Nonetheless, glutamate that diffuses out of the synaptic cleft can have actions at distant receptors, a mode of transmission called spillover. To uncover the extrasynaptic actions of glutamate, we localized AMPA receptors (AMPARs) mediating spillover transmission between climbing fibers and molecular layer interneurons in the cerebellar cortex. We found that climbing fiber spillover generates calcium transients mediated by Ca2+-permeable AMPARs at parallel fiber synapses. Spillover occludes parallel fiber synaptic currents, indicating that separate, independently regulated afferent pathways converge onto a common pool of AMPARs. Together these findings demonstrate a circuit motif wherein glutamate ‘spill-in’ from an unconnected afferent pathway co-opts synaptic receptors, allowing activation of postsynaptic AMPARs even when canonical glutamate release is suppressed

Dynamic functions of GABA signaling during granule cell maturation

The dentate gyrus is one of the few areas of the brain where new neurons are generated throughout life. Neural activity influences multiple stages of neurogenesis, thereby allowing experience to regulate the production of new neurons. It is now well established that GABAA receptor-mediated signaling plays a pivotal role in mediating activity-dependent regulation of adult neurogenesis. GABA first acts as a trophic signal that depolarizes progenitors and early post mitotic granule cells, enabling network activity to control molecular cascades essential for proliferation, survival and growth. Following the development of glutamatergic synaptic inputs, GABA signaling switches from excitatory to inhibitory. Thereafter robust synaptic inhibition enforces low spiking probability of granule cells in response to cortical excitatory inputs and maintains the sparse activity patterns characteristic of this brain region. Here we review these dynamic functions of GABA across granule cell maturation, focusing on the potential role of specific interneuron circuits at progressive developmental stages. We further highlight questions that remain unanswered about GABA signaling in granule cell development and excitability

GABAergic signalling to adult-generated neurons

New neurons are continuously generated in discrete regions of the adult brain. In the hippocampus, newly generated cells undergo a step-wise progression of maturation that is regulated at multiple stages by a variety of physiological and pathological stimuli. Neural progenitors and newborn neurons initially receive exclusively GABAergic synaptic input, and accumulating evidence suggests that depolarizing actions of GABA contribute to activity-dependent regulation. Here we provide a brief overview of GABAergic signalling to newborn neurons in the hippocampus and describe how it regulates adult neurogenesis

New Neurons in the Adult Mammalian Brain: Synaptogenesis and Functional Integration

New neurons are continuously added in the olfactory bulb and dentate gyrus of the hippocampus throughout adult life (Kem- permann and Gage, 1999; Temple and Alvarez-Buylla, 1999; Schinder and Gage, 2004; Lledo and Saghatelyan, 2005; Ming and Song, 2005). This adult form of neurogenesis represents a previ- ously unrecognized structural and functional plasticity in the ma- ture mammalian brain, including in humans. Now it is well es- tablished that adult-born dentate granule cells (DGCs) can functionally integrate into the existing circuitry (Carlen et al., 2002; van Praag et al., 2002; Jessberger and Kempermann, 2003; Schmidt-Hieber et al., 2004). However, little is known about how that occurs and what is the contribution of new DGCs to the overall hippocampal function. Accumulating evidence suggests that adult neurogenesis is involved in many physiological and pathological conditions, such as learning and memory, epilepsy, mental disorders, and degenerative neurological diseases (Ming and Song, 2005). The impact of new neurons on the adult neu- ronal circuitry is determined by their physiological properties and synaptic connectivity. This mini-symposium presented at the 2005 Society for Neuroscience Meeting will provide insight into how newly generated neurons become synaptically inte- grated into the existing circuitry of the adult brain, with emphasis on the physiological properties of newborn DGCs in the hippocampus.Fil: Song, Hongjun. University Johns Hopkins; Estados UnidosFil: Kempermann, Gerd. Max Delbrück Center for Molecular Medicine Berlin Buch; AlemaniaFil: Overstreet Wadiche, Linda. University of Oregon; Estados UnidosFil: Zhao, Chunmei. Salk Institute for Biological Studies; Estados UnidosFil: Schinder, Alejandro Fabián. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Bischofberger, Josef. University of Freiburg; Alemani