The Timing for Neuronal Maturation in the Adult Hippocampus Is Modulated by Local Network Activity

Abstract

The adult hippocampus continuously generates new cohorts of immature neurons with increased excitability and plasticity. The window for the expression of those unique properties in each cohort is determined by the time required to acquire a mature neuronal phenotype. Here, we show that local network activity regulates the rate of maturation of adult-born neurons along the septotemporal axis of the hippocampus. Confocal microscopy and patch-clamp recordings were combined to assess marker expression, morphological development, and functional properties in retrovirally labeled neurons over time. The septal dentate gyrus displayed higher levels of basal network activity and faster rates of newborn neuron maturation than the temporal region. Voluntary exercise enhanced network activity only in the temporal region and, in turn, accelerated neuronal development. Finally, neurons developing within a highly active environment exhibited a delayed maturation when their intrinsic electrical activity was reduced by the cell-autonomous overexpression of Kir2.1, an inward-rectifying potassium channel. Our findings reveal a novel type of activity-dependent plasticity acting on the timing of neuronal maturation and functional integration of newly generated neurons along the longitudinal axis of the adult hippocampus.

Retrograde monosynaptic tracing reveals the temporal evolution of inputs onto new neurons in the adult dentate gyrus and olfactory bulb

“…As our analyses of the temporal evolution of presynaptic connectivity were confined to running mice, it cannot be excluded that such a pattern reflects the increase in hippocampal network activity as a result of physical activity. In fact, running mice exhibited an increase in presynaptic connectivity compared with sedentary mice, consistent with previous findings (20), suggesting that physical activity can alter the time course of integration.…”

“…1D). Voluntary exercise is known to increase cell proliferation, survival, and synaptogenesis of newborn neurons in the DG (19,20). Although we observed an increase in retroviral transduction efficiency in animals subjected to voluntary wheel running, as reported previously (19), the number of primary RABV-infected starter cells was only moderately changed.…”

LIS1 Deficiency Promotes Dysfunctional Synaptic Integration of Granule Cells Generated in the Developing and Adult Dentate Gyrus

“…Recent studies revealed septotemporal differences in the rate of granule cell proliferation, survival, and connectivity in the adult hippocampus (Jinno, 2011;Piatti et al, 2011). Surprisingly, our findings reveal that the ectopic position of adult-born granule cells influenced their functional maturation and integration.…”

“…Local network activity is one of the most widely characterized modulators of granule cell development in the adult brain. Conditions of heightened excitability in DG are generally believed to accelerate the proliferation, maturation, and integration of adult-born granule cells Piatti et al, 2011), but synaptic connections to granule cells born into a malformed DG have not been investigated. Therefore, we examined whether the functional integration or maturation of EGFP-labeled newly born granule cells was altered in heterozygous LIS1 mutant mice.…”

“…The adult DG generates new neurons that migrate and integrate into an existing hippocampal circuitry-a process sensitive to environmental factors (Kempermann et al, 1997;Tashiro et al, 2007) and local network activity (Piatti et al, 2011). Moreover, disrupting adult neurogenesis may support seizure generation (Parent et al, 1997) or modify cognition (Arruda-Carvalho et al, 2011).…”