Brenda J. Claiborne

Neurons, numbers and the hippocampal network

Anatomists involved with studies of the hippocampal formation are being prodded by computational modelers and physiologists who demand detailed and quantitative information concerning hippocampal neurons and circuits. The beautiful camera lucida drawings of old, and the elegant descriptions of dendritic form that accompanied them are giving way to computer-reconstructed and three-dimensionally analyzed cells with rigorous determination of dendritic lengths and volumes, branching pattern and spine distribution. We will review certain quantitative aspects of hippocampal organization in the rat based on a survey of available literature and on our own intracellular labeling studies of granule cells of the dentate gyrus and pyramidal cells of the hippocampus. Some of the potential implications of these data for hippocampal information processing will be discussed.

Dendritic growth and regression in rat dentate granule cells during late postnatal development

The goal of this study was to determine whether dendritic regression occurs in granule neurons of the rat dentate gyrus during late postnatal development. In vitro hippocampal slices were prepared from rats between the ages of 14 and 60 days, and granule neurons in one portion of the suprapyramidal blade were labeled by intracellular injection of horseradish peroxidase. The dendrites of filled neurons were analyzed in both two and three dimensions directly from 400 microns thick whole-mounts. Results showed that the molecular layer expanded by approximately 50% between days 14 and 60. At every age examined, granule cell dendrites reached the top of the molecular layer, suggesting that dendrites continued to grow during this time period. In contrast, the number of dendritic segments per neuron decreased from an average of 36 to 28. Three-dimensional measurements showed that total dendritic length and surface area per granule cell did not change, suggesting that the overall dendritic tree size of granule neurons may be regulated during late postnatal development in the rodent.

Distribution of thorny excrescences on CA3 pyramidal neurons in the rat hippocampus

Thorny excrescences are the postsynaptic components of synapses between mossy fibers of granule cells and dendrites of CA3 pyramidal neurons in the hippocampal formation. Very little quantitative data on the number and distribution of excrescences in adult rats are available because, first, the vast majority are grouped into clusters and it is not possible to identify single excrescences within these clusters at the light microscope level. Second, clusters are of varying lengths and are distributed over hundreds of micrometers, making ultrastructural analysis prohibitively time‐consuming. Here, by using three‐dimensional analysis techniques at the light microscope level, we quantified the number, length, and distribution of excrescence clusters on proximal and midfield pyramidal neurons in the rat. Results indicated that proximal neurons had similar numbers of clusters on their apical and basal trees, and that cluster length was also similar. In contrast, midfield neurons had more apical than basal clusters, and apical clusters were longer. For neurons in both regions, basal clusters were located about 50% closer to somata. Overall, proximal neurons had more clusters than did midfield neurons, but the clusters were shorter; thus, proximal and midfield neurons had about the same total cluster length, and presumably the same number of single excrescences. Based on these data and on published ultrastructural measurements of single excrescences, we estimated an average of 41 excrescences/neuron, and suggest that a pyramidal neuron can be contacted by a maximum of 41 mossy fiber boutons, each from a different granule cell. J. Comp. Neurol. 430:357–368, 2001.

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.

Hebbian computations in hippocampal dendrites and spines

Publisher Summary This chapter discusses the Hebbian computation in hippocampal dendrites and spines by considering three abstract dimensions of differences, namely, space, time, and probability. It also focuses on the implications of spatial differences between neurons and processing elements (PEs). Determination of synaptic modifications can be done in part by the local dendritic potential, and the dendritic potential can be affected by the outcome of the modifications. Depending on the properties of the dendrites, this reciprocal relationship can easily be imagined to produce categories of adaptive computations. Preliminary simulations suggest that the electrotonic structure of neurons adds a computational complexity that is not present in PEs and the structure may be an important determinant of the manner in which synaptic strengths self-organize in response to a structured environment.

Pubertal exposure to anabolic androgenic steroids increases spine densities on neurons in the limbic system of male rats.

Human studies show that the number of teenagers abusing anabolic androgenic steroids (AAS) is increasing. During adolescence, brain development is altered by androgen exposure, which suggests that AAS may potentially alter central nervous system (CNS) development. The goal of the present study was to determine whether pubertal AAS exposure increased dendritic spine densities on neurons within the medial amygdala and the dorsal hippocampus. Pubertal gonadally intact male rats received the AAS testosterone propionate (5 mg/kg) or vehicle for 5 days/week for 4 weeks. To determine the long-term implications of pubertal AAS use, another set of males received the same AAS treatment and was then withdrawn from AAS exposure for 4 weeks. Results showed that pubertal AAS exposure significantly increased spine densities on neurons in the anterior medial amygdala, posterodorsal medial amygdala, and the cornu ammonis region 1 (CA1) of the hippocampus compared with gonadally intact control males. Spine densities returned to control levels within the anterior medial amygdala and the posterodorsal medial amygdala 4 weeks after withdrawal. However, spine densities remained significantly elevated after AAS withdrawal in the CA1 region of the hippocampus, suggesting that pubertal AAS exposure may have a long-lasting impact on CA1 hippocampal neuroanatomy. Since pubertal AAS exposure increased spine densities and most excitatory synapses in the CNS occur on dendritic spines, AAS may increase neuronal excitation. It is proposed that this increase in excitation may underlie the behavioral responses seen in pubertal AAS-treated male rats.

Computational models of hippocampal neurons

Publisher Summary This chapter describes the methods and their rationale, focusing on pyramidal neurons of the CA1 region of the hippocampus. It discusses the way the morphometric and neurophysiological properties can be combined and incorporated into compartmental models that enable efficient simulations. The chapter also describes the graphical display system, which is found to be essential for interpreting the results of the simulations. To create an electrotonic model, three electrical properties of the cell needs be specified: R m , the specific membrane resistivity; C m , the specific membrane capacitance; and R i , the specific resistivity of the cytoplasm. If these are assumed to be homogeneous throughout the neuron, and if one neglect the problem of a somatic shunt, then these three parameters, in conjunction with the morphology, uniquely determine the neurons electrotonic structure. Field of computational neuroscience can be expected to furnish the theoretical glue that is needed to integrate and comprehend the explosion of experimental knowledge.

Efficient mapping from neuroanatomical to electrotonic space

Previous studies documented the importance of electrotonic structure in single-neuron computations. Here we elaborate a new approach to electrotonic theory and analysis. We begin with a more versatile measure Lij of the electrotonic distance between any two locations i and j on a neuron. If Vi is the voltage at the origin and Vj is the voltage at Some other point, the electrotonic distance is Lij=ln(Vi/Vj). Voltage decays e-fold per unit of L for any two points on the neuron, regardless of its electrotonic architecture. Lij increases as the sinusoidal frequency of Vi increases. If j lies on the direct path between i and k, then Lik=Lij+Ljk. This relation enables electrotonic transforms of the neuron—graphical mappings from neuroanatomical to electrotonic space. For each neuron, there exists an infinite number of such transforms, which can be done from any reference location on the neuron, as a function of voltage transfer to or from that location, and for any frequency of input signal. Sets of these trans...

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

Estrogens 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.

Detection of zinc in isolated nerve terminals using a modified Timm's sulfide―silver method

An ultrastructural method for detecting the presence of zinc in isolated nerve terminals from the mammalian brain is described. This method is based on the well-known Timms sulfide-silver technique that has been used by many investigators to detect and localize zinc-containing pathways in sections of intact brain tissue. We report here a modification of this technique that we have used to assess the homogeneity, at the electron microscopic level, of a zinc-enriched synaptosomal fraction from the rat hippocampus. This technique allows biochemical assays to be performed on samples of the same tissue if desired, and also provides the large amounts of tissue needed for synaptosomal isolation. Results indicated that all of the mossy fiber synaptosomes, identified on the basis of their large size and characteristic morphology, stained for zinc using this method, as did about one-third of the smaller synaptic profiles present in the same fraction. The method described here should be useful for determining zinc retention and localization in isolated synaptosomes from other regions of the mammalian central nervous system.