Granule neurons generated during development extend divergent axon collaterals to hippocampal area CA3

Abstract

Most excitatory intrahippocampal pathways are characterized by significant, highly ordered projections into the long, or septotemporal, hippocampal axis. However, the mossy fiber system, the excitatory projection by which the dentate gyrus projects to hippocampal area CA3, is considered an exception, being organized to innervate exclusively transversely oriented cortical layers of the hippocampus. In the present study, the anatomy of the rat mossy fiber system was investigated using axonal tracing techniques, with an emphasis on determining its projection pattern into the long hippocampal axis. To this end, we used dual ipsilateral retrograde tracer injections to determine whether individual granule cells extend divergent axon collaterals to septotemporally distinct levels of hippocampal area CA3. We combined this technique with the fluorescent immunohistochemical detection of 5-bromo-2Ј-deoxyuridine (BrdU), a marker of granule cell precursors and their progeny, to address whether the divergence of mossy fiber collaterals within area CA3 might by related to ontogenic gradients in granule cell genesis. We observed single granule neurons that had retrogradely transported both tracers, indicating that they had axon collaterals passing through or terminating within the distinct levels of area CA3 into which tracer had been injected. By using BrdU labeling, we identified divergent granule neurons that were produced during embryonic and postnatal development. We observed no adult-generated granule neurons with significantly diverging mossy fiber collaterals. However, many fewer cells were labeled with BrdU in adult-exposed animals. Because of this smaller sample, we cannot rule out the possibility that small numbers of divergent adult-generated granule cells exist. We conclude that a proportion of the hippocampal mossy fiber projection extends septotemporally divergent axon collaterals to hippocampal area CA3.

A natural form of learning can increase and decrease the survival of new neurons in the dentate gyrus

“…In contrast, the density of unlabeled pyknotic cells in the sgz, reflecting death of adult-born granule cells with a wide range of ages and maturity levels, was increased in all groups of rats that were removed from the housing facility the day before testing, while pyknotic cells in the outer gcl, where the oldest granule cells are located, were increased in all rats that were tested. Interestingly, the loss of these cells in the outer gcl, which are likely to have the largest axonal projections (Gaarskjaer, 1981;Hastings et al, 2002), is predicted by modeling to improve future learning by the network (Chambers et al, 2004).…”

Effect of Cancer Treatment on Neural Stem and Progenitor Cells

“…11,12,16 In the hippocampus, NSCs give rise to new granule cells that are functionally integrated in the existing neuronal network. [17][18][19][20][21] In addition to the main germinal zones of the CNS -the lateral subventricular zone and the hippocampus -small numbers of NSCs have also been identified in other brain regions, such as the subcortical white matter, 22 cerebral corte 23,24 and retina. 25 It has been suggested that different NSC populations exist in the CNS, and both cell intrinsic and local environmental signals contribute to the presence of regionally different NSC populations.…”

Postnatal neurogenesis in the dentate gyrus of the guinea pig

“…The production of a substantial number of new granule cells has been demonstrated to continue into adulthood in rodents, nonhuman primates and humans (Cameron et al, 1993;Gould et al, 1997Gould et al, , 1999bEriksson et al, 1998;Kornack and Rakic, 1999;Roy et al, 2000;Seri et al, 2001). Newly formed granule cells migrate into the granular layer, send their axons (the mossy fibers) to CA3 field (Hastings and Gould, 1999;Markakis and Gage, 1999;Hastings et al, 2002), and mature into functional neurons that are incorporated into the major hippocampal circuit (granule cells-CA3-CA1 loop) (van Praag et al, 2002). These new neurons are thought to play a significant role in hippocampal synaptic plasticity (Snyder et al, 2001).…”