Publications (5)50.05 Total impact
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Article: Unique processing during a period of high excitation/inhibition balance in adult-born neurons.
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ABSTRACT: 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.Science 03/2012; 335(6073):1238-42. · 31.20 Impact Factor -
Article: The timing for neuronal maturation in the adult hippocampus is modulated by local network activity.
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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.Journal of Neuroscience 05/2011; 31(21):7715-28. · 7.11 Impact Factor -
Article: Adult neurogenesis and the plasticity of the dentate gyrus network.
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ABSTRACT: The granule cell layer (GCL) of the dentate gyrus contains neurons generated during embryonic, early postnatal and adult life. During adulthood there is a continuous production of neuronal cohorts that develop and functionally integrate in the preexisting circuits. This morphogenic process generates a stratified GCL, with the outermost layers containing dentate granule cells (DGCs) generated during perinatal life, and the innermost layers containing adult-born DGCs. In this review we analyse the functional profile of the different neuronal populations of the GCL, with an emphasis on adult-born neurons as they develop, mature and integrate in the dentate gyrus network. We focus on the contribution of adult-born neurons to activity-dependent synaptic modification in the dentate gyrus and, in turn, discuss how network activity modulates integration and survival of new neurons.European Journal of Neuroscience 03/2011; 33(6):1055-61. · 3.63 Impact Factor -
Article: Reliable activation of immature neurons in the adult hippocampus.
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ABSTRACT: Neurons born in the adult dentate gyrus develop, mature, and connect over a long interval that can last from six to eight weeks. It has been proposed that, during this period, developing neurons play a relevant role in hippocampal signal processing owing to their distinctive electrical properties. However, it has remained unknown whether immature neurons can be recruited into a network before synaptic and functional maturity have been achieved. To address this question, we used retroviral expression of green fluorescent protein to identify developing granule cells of the adult mouse hippocampus and investigate the balance of afferent excitation, intrinsic excitability, and firing behavior by patch clamp recordings in acute slices. We found that glutamatergic inputs onto young neurons are significantly weaker than those of mature cells, yet stimulation of cortical excitatory axons elicits a similar spiking probability in neurons at either developmental stage. Young neurons are highly efficient in transducing ionic currents into membrane depolarization due to their high input resistance, which decreases substantially in mature neurons as the inward rectifier potassium (Kir) conductance increases. Pharmacological blockade of Kir channels in mature neurons mimics the high excitability characteristic of young neurons. Conversely, Kir overexpression induces mature-like firing properties in young neurons. Therefore, the differences in excitatory drive of young and mature neurons are compensated by changes in membrane excitability that render an equalized firing activity. These observations demonstrate that the adult hippocampus continuously generates a population of highly excitable young neurons capable of information processing.PLoS ONE 02/2009; 4(4):e5320. · 4.09 Impact Factor -
Article: Evidence for different gonadotropin-releasing hormone response sites in rat ovarian and pituitary cells.
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ABSTRACT: The participation of type I GnRH receptor (GnRH-R) on GnRH-II-induced gonadotropin secretion in rat pituitary cells was investigated. Furthermore, we extended the study of GnRH-II action to ovarian cells. The GnRH-II was able to mobilize inositol triphosphate (IP(3)) and to induce LH and FSH release in a dose-dependent manner in pituitary cells and in a GnRH-I-like manner. The GnRH-analog 135-18 (agonist for type II GnRH-R and antagonist for type I GnRH-R) was unable to elicit any cellular response tested in these pituitary cells. The GnRH-II responses were blocked by the type I GnRH-R-antagonists CRX or 135-18, suggesting that these effects were mediated by the type I GnRH-R. In contrast to pituitary cells, GnRH-I, but not GnRH-II, elicited an IP(3) response in superovulated ovarian cells; 135-18 also had no effect. However, GnRH-II as well as GnRH-I presented antiproliferative effects on these cells. Surprisingly, 135-18 had stronger antiproliferative effects than either GnRH peptide. The 135-18 analog, but not GnRH-I or GnRH-II, increased progesterone secretion in superovulated ovarian cells. These results strongly suggest that GnRH-II is able to stimulate rat pituitary cells through the type I GnRH-R, with no evidence for the presence of type II GnRH-R. On the other hand, our results indicate a putative GnRH-R in superovulated ovarian cells with response characteristics that differ from those of the GnRH-R in the pituitary.Biology of Reproduction 09/2004; 71(2):464-9. · 4.01 Impact Factor
Top Journals
- Biology of Reproduction (1)
- Science (1)
- European Journal of Neuroscience (1)
- Journal of Neuroscience (1)
- PLoS ONE (1)
Institutions
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2011–2012
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National Council of Scientific and Technical Research
Buenos Aires, Buenos Aires F.D., Argentina
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2009
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Fundación Instituto Leloir
Buenos Aires, Buenos Aires F.D., Argentina
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2004
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Instituto de Biología y Medicina Experimental
Buenos Aires, Buenos Aires F.D., Argentina
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