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Scientific Understanding of Consciousness |
Hippocampal Neurogenesis in Adult
Science 9 March 2012: Vol. 335 no. 6073 pp. 1238-1242 Unique Processing During a Period of High Excitation/Inhibition Balance in Adult-Born Neurons Antonia Marín-Burgin, Lucas A. Mongiat, M. Belén Pardi, Alejandro F. Schinder Laboratorio de Plasticidad Neuronal, Instituto Leloir, Instituto de Investigaciones Bioquímicas de Buenos Aires–Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Avenida Patricias Argentinas 435, 1405 Buenos Aires, Argentina. [paraphrase] The adult dentate gyrus generates new granule cells (GCs) that develop over several weeks and integrate into the preexisting network. Although adult hippocampal neurogenesis has been implicated in learning and memory, the specific role of new GCs remains unclear. We examined whether immature adult-born neurons contribute to information encoding. By combining calcium imaging and electrophysiology in acute slices, we found that weak afferent activity recruits few mature GCs while activating a substantial proportion of the immature neurons. These different activation thresholds are dictated by an enhanced excitation/inhibition balance transiently expressed in immature GCs. Immature GCs exhibit low input specificity that switches with time toward a highly specific responsiveness. Therefore, activity patterns entering the dentate gyrus can undergo differential decoding by a heterogeneous population of GCs originated at different times. The adult hippocampus continuously generates new neurons that integrate in the dentate gyrus network and become relevant for information processing during specific learning tasks. Experimental manipulations that reduce adult neurogenesis produce impairment of hippocampus-dependent learning and behavior. Yet, the specific traits that determine the functional relevance of adult-born neurons remain unknown. Is it solely the continuous addition of new neurons to the network that is important, or are there specific functional properties only attributable to new granule cells (GCs) that are relevant to information processing? When reaching maturity, adult-born GCs exhibit functional properties that are indistinguishable from GCs generated during development. However, while developing, immature GCs display elevated intrinsic excitability, reduced γ-aminobutyric acid (GABA)–mediated inhibition, and enhanced capacity to undergo activity-dependent synaptic potentiation. Such high intrinsic excitability would potentially allow immature GCs to be activated by entorhinal afferents in spite of their low density of glutamatergic inputs. It has thus recently been hypothesized that immature GCs might be critical to hippocampal function. First, we investigated how immature GCs process afferent activity from entorhinal inputs and how they compare with mature GCs in the adult mouse hippocampus. Our data demonstrate that immature GCs exhibit all of the features required to process information and display a low activation threshold due to an enhanced excitation/inhibition balance at the time of spike initiation. At this early developmental stage, they already release glutamate onto CA3 pyramidal cells. As a consequence, neuronal activity in the dentate gyrus is biased toward the immature population of principal neurons that bypass inhibitory control, whereas the activation of mature neurons is limited by inhibition. This is in contrast to other areas of the hippocampus and neocortex, in which inhibition exerts a global (homogeneous) control in the activity of principal cells. Hence, adult neurogenesis emerges as a mechanism that generates a distinct type of network heterogeneity. In addition, the differential control of inhibition revealed here constitutes a simple synaptic mechanism that could underlie the enhanced capacity of immature GCs to undergo activity-dependent synaptic potentiation when GABAergic inhibition is left intact. In the context of the low activation threshold described here, the increased plasticity might provide an efficient means for strengthening and reinforcing weak synaptic inputs that are repeatedly activated during a restricted time window. The observed network heterogeneity may be crucial for the integration and separation of spatial patterns, properties that have been attributed to the dentate gyrus. Their low activation threshold and low input specificity make immature GCs appropriate substrates for pattern integration—a feature that has been proposed in computational models of adult neurogenesis. In this context, immature neurons represent a population of integrators that are broadly tuned during a transient period and may encode most features of the incoming afferent information. When becoming mature, new GCs display a high activation threshold and input specificity and will, therefore, become good pattern separators. Adult neurogenesis would then maintain the renewable cohorts of highly integrative GCs in the dentate gyrus. Last, the functional properties described here support a hypothesis in which activity reaching the dentate gyrus could undergo differential decoding through immature neuronal cohorts that are highly responsive and integrative and, in parallel, through a large population of mature GCs with sparse activity and high input specificity. [end of paraphrase]
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