Morphological development and maturation of granule neuron dendrites in the rat dentate gyrus

Abstract

The first granule neurons in the dentate gyrus are born during late embryogenesis in the rodent, and the primary period of granule cell neurogenesis continues into the second postnatal week. On the day of birth in the rat, the oldest granule neurons are visible in the suprapyramidal blade and exhibit rudimentary dendrites extending into the molecular layer. Here we describe the morphological development of the dendritic trees between birth and day 14, and we then review the process of dendritic remodeling that occurs after the end of the second week. Data indicate that the first adult-like granule neurons are present on day 7, and, furthermore, physiological recordings demonstrate that some granule neurons are functional at this time. Taken together, these results suggest that the dentate gyrus may be incorporated into the hippocampal circuit as early as the end of the first week. The dendritic trees of the granule neurons, however, continue to increase in size until day 14. After that time, the dendritic trees of the oldest granule neurons are sculpted and refined. Some dendrites elongate while others are lost, resulting in a conservation of total dendritic length. We end this chapter with a review of the quantitative aspects of granule cell dendrites in the adult rat and a discussion of the relationship between the morphology of a granule neuron and the location of its cell body within stratum granulosum and along the transverse axis of the dentate gyrus.

Introduction

Granule neurons are the principal cell type in the dentate gyrus, and their cell bodies are located in stratum granulosum of the suprapyramidal and infrapyramidal blades. Dendrites extend from the apical pole of the granule cell body into the overlying molecular layer, and the axon, or mossy fiber, exits from the basal pole. The axon gives rise to collateral branches in the hilar region and then forms synapses on pyramidal neurons in the CA3 region of the hippocampus proper. The apical dendrites of the granule neurons bifurcate as they traverse the molecular layer, and the vast majority of terminal branches reach the top of the layer in the adult. The dendritic trees of most granule neurons are elliptical, and all dendrites of granule neurons in the adult dentate gyrus are covered with spines.

The primary period of granule cell neurogenesis occurs over a two- to three-week period in the rodent, beginning in late embryogenesis and continuing through the second postnatal week. In the rat, although a few granule neurons are born as early as embryonic day 14, over 80% are born after the birth of the animal (which occurs at about embryonic day 21) and neurogenesis peaks near the end of the first week of life (Bayer and Altman, 1974; Schlessinger et al., 1975). It is worth noting that the granule neurons are the last cells to be generated in the hippocampal formation, and it is well known that granule cell neurogenesis continues into adulthood (Altman and Das, 1965; Kaplan and Hinds, 1977). Here we focus on granule neurons that are generated in the neonatal rat. From recent evidence in the mouse, it appears that adult-generated granule neurons progress through a similar set of stages as they develop and mature (Zhao et al., 2006).

Any description of the development and maturation of the granule neurons must take into account the temporal and spatial gradients of granule cell neurogenesis (Schlessinger et al., 1975; Cowan et al., 1981, Cowan et al., 1980). The earliest born granule neurons form stratum granulosum in the septal portion of the dentate gyrus, and neurons that are generated later form the more temporal portions of the dentate gyrus. This gradient is referred to as the septotemporal gradient. A second gradient exists along the transverse axis of the dentate gyrus and is of considerable importance for developmental and morphological studies. As the first granule neurons are born, they form the cell-body layer at the tip of the suprapyramidal blade. As additional neurons are generated, they form the cell-body layer in the middle of the suprapyramidal blade and then the portions of stratum granulosum closest to the crest region. This gradient continues as more neurons are generated such that the youngest neurons make up stratum granulosum in the infrapyramidal blade. A third gradient exists within stratum granulosum. The neurons that are born first move into their final position at the top of the cell-body layer near the molecular layer, and the younger neurons move into position beneath them such that they are located in the bottom portion of stratum granulosum near the hilar border. This developmental pattern is in contrast to the “inside-out” pattern found in other areas of the mammalian cerebral cortex in which the later-generated neurons move through the earlier-generated cells to occupy positions at the top of the cell-body layer.

Thus the oldest granule neurons are most likely to be found at the top of stratum granulosum near the distal tip of the suprapyramidal blade at the septal pole, whereas the youngest neurons are located predominantly in the infrapyramidal blade near the temporal pole and in the deeper portions of stratum granulosum along the entire extent of the transverse axis of the dentate gyrus. In the rat, the suprapyramidal blade begins to form in late embryogenesis as the first granule neurons are born — it is visible as a separate structure on the day of birth and consists of a cell-body layer and a relatively thin molecular layer (Cowan et al., 1980). The molecular layer increases greatly in width over the first several weeks. It is less than 100 μm at day 4 and increases to just over 200 μm at day 14; it averages approximately 300 μm in width in young adult rats (Loy et al., 1977; Claiborne et al., 1990; Rihn and Claiborne, 1990). The infrapyramidal blade is barely visible on the day of birth and grows more slowly than the suprapyramidal blade during the first week, increasing from approximately 45 μm in width on day 4 to approximately 110 μm on day 10; it measures between 205 and 240 μm in young adult rats (Loy et al., 1977; Claiborne et al., 1990).

Here we describe the development and maturation of the dendritic trees of the granule neurons in the rat, and we review the quantitative data on dendritic morphology in the adult. We consider the developmental period to encompass the time from the birth of the animal through day 14. By day 14, the oldest granule neurons have assumed their adult form and size. From day 14 to 60, however, the neurons go through a period of maturation during which the dendritic tree is sculpted and refined and the density of spines continues to increase. The dendritic trees of granule neurons appear to be mature by day 60: unpublished data from our lab indicate that they do not undergo any quantitative changes between 60 and 180 days.