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

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.

Estradiol's effects on learning and neuronal morphology vary with route of administration.

Estrogen's effects on performance and neuronal morphology are variable, and the reasons for this variability are not yet understood. In this study, the authors compared the effects of 2 delivery routes of 17 beta-estradiol on spatial learning and dendritic spine densities in young ovariectomized rats; estradiol was administered by implanted capsules or by daily oral gavage. Estradiol treatment via capsules improved performance in the radial-arm water maze and increased spine densities on dendrites of CA1 pyramidal neurons in the hippocampal formation. In contrast, daily oral administration of estradiol did not affect either measure. These data demonstrate that estradiol delivery is a critical variable in animal studies and that clinical studies comparing the effects of different estradiol treatment routes on cognition are warranted.

Distinct patterns of gene expression in the left and right hippocampal formation of developing rats.

A central problem in neurobiology is the elucidation of the mechanisms that underlie left-right asymmetries in brain structure and function. Using a transcriptome screening approach, we found asymmetric gene expression patterns in the right when compared with the left hippocampal formation at postnatal days (P) 6, 9, and 60 in the rat. Of those genes that were differentially expressed, most were predominantly expressed in the right hippocampus at P6, whereas most were predominantly expressed in the left at P9 and P60. Real-time PCR analysis of genes associated with synaptic vesicle trafficking confirmed this pattern. At P6, 9 of 13 such genes were more robustly expressed in the right hippocampus, while only 1 gene was predominantly expressed in the left. Conversely, at P9, 5 of the 13 genes were more highly expressed in the left hippocampus and only 1 gene was predominantly expressed in the right. This pattern persisted at P60: eight genes were more robustly expressed in the left hippocampus, and the remaining five showed no hemispheric preference. These data demonstrate a pattern of early lateralized gene expression that is likely to underlie the establishment of functional asymmetry in the adult hippocampus.

In vivo recordings of long-term potentiation and long-term depression in the dentate gyrus of the neonatal rat.

Previous in vitro studies demonstrated that long-term potentiation (LTP) could be elicited at medial perforant path (MPP) synapses onto hippocampal granule cells in slices from 7-day-old rats. In contrast, in vivo studies suggested that LTP at perforant path synapses could not be induced until at least days 9 or 10 and then in only a small percentage of animals. Because several characteristics of the oldest granule cells are adult-like on day 7, we re-examined the possibility of eliciting LTP in 7-day-old rats in vivo. We also recorded from 8- and 9-day-old rats to further elucidate the occurrence and magnitude of LTP in neonates. With halothane anesthesia, all animals in each age group exhibited synaptic plasticity of the excitatory postsynaptic potential following high-frequency stimulation of the MPP. In 7-day-old rats, LTP was elicited in 40% of the animals and had an average magnitude of 143%. Long-term depression (LTD) alone (magnitude of 84%) was induced in 40% of the animals, while short-term potentiation (STP) alone (magnitude of 123%) was induced in 10%. STP followed by LTD was elicited in the remaining 10%. Data were similar for all ages combined. In addition, the N-methyl-d-aspartate (NMDA) antagonist (R,S)-3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid (CPP) blocked the occurrence of LTP at each age and doubled the percentage of animals expressing LTD alone for all ages combined. These results demonstrate that tetanic stimulation can elicit LTP or LTD at MPP synapses in 7-day-old rats, supporting our premise that at least a portion of the dentate gyrus is functional at this early age.

Maturation of granule cell dendrites after mossy fiber arrival in hippocampal field CA3.

Most granule neurons in the rat dentate gyrus are born over the course of the first 2 postnatal weeks. The resulting heterogeneity has made it difficult to define the relationship between dendritic and axonal maturation and to delineate a time course for the morphological development of the oldest granule neurons. By depositing crystals of the fluorescent label Dil in hippocampal field CA3, we retrogradely labeled granule neurons in fixed tissue slices from rats aged 2-9 days. The results showed that all labeled granule cells, regardless of the age of the animal, exhibited apical dendrites. On day 2, every labeled neuron had rudimentary apical dendrites, and a few dendrites on each cell displayed immature features such as growth cones, varicosities, and filopodia. Some cells displayed basal dendrites. By day 4, the most mature granule neurons had longer and more numerous apical branches, as well as various immature features. Most had basal dendrites. On days 5 and 6, the immature features and the basal dendrites had begun to regress on the oldest cells, and varying numbers of spines were present. On day 7, the first few adult-like neurons were seen: immature features and basal dendrites had disappeared, all dendrites reached the top of the molecular layer, and the entire dendritic tree was covered with spines. These data show that dendritic outgrowth occurs before, or concurrent with, axon arrival in the CA3 target region, and that adult-like granule neurons are present by the end of the first week.