Changes In Dendritic Length Research Articles

Selective Loss of Thin Spines in Area 7a of the Primate Intraparietal Sulcus Predicts Age-Related Working Memory Impairment.

Brodmann area 7a of the parietal cortex is active during working memory tasks in humans and nonhuman primates, but the composition and density of dendritic spines in area 7a and their relevance both to working memory and cognitive aging remain unexplored. Aged monkeys have impaired working memory, and we have previously shown that this age-induced cognitive impairment is partially mediated by a loss of thin spines in prefrontal cortex area 46, a critical area for working memory. Because area 46 is reciprocally connected with area 7a of the parietal cortex and 7a mediates visual attention integration, we hypothesized that thin spine density in area 7a would correlate with working memory performance as well. To investigate the synaptic profile of area 7a and its relevance to working memory and cognitive aging, we investigated differences in spine type and density in layer III pyramidal cells of area 7a in young and aged, male and female rhesus macaques (Macaca mulatta) that were cognitively assessed using the delayed response test of working memory. Area 7a shows age-related loss of thin spines, and thin spine density positively correlates with delayed response performance in aged monkeys. In contrast, these cells show no age-related changes in dendritic length or branching. These changes mirror age-related changes in area 46 but are distinct from other neocortical regions, such as V1. These findings support our hypothesis that cognitive aging is driven primarily by synaptic changes, and more specifically by changes in thin spines, in key association areas.SIGNIFICANCE STATEMENT This study advances our understanding of cognitive aging by demonstrating the relevance of area 7a thin spines to working memory performance. This study is the first to look at cognitive aging in the intraparietal sulcus, and also the first to report spine or dendritic measures for area 7a in either young adult or aged nonhuman primates. These results contribute to the hypothesis that thin spines support working memory performance and confirm our prior observation that cognitive aging is driven by synaptic changes rather than changes in dendritic morphology or neuron death. Importantly, these data show that age-related working memory changes are not limited to disruptions of the prefrontal cortex but also include an association region heavily interconnected with prefrontal cortex.

Increased dendritic length in CA1 and CA3 hippocampal neurons during the metestrus phase in Wistar rats

Studies have shown that changes in ovarian hormone concentrations promote natural fluctuations in the density of dendritic spines of hippocampal neurons in female Sprague-Dawley rats, without changes in dendritic length, throughout the estrous cycle. However, it is still unknown whether these fluctuations are present in other rat strains. Due to our interest in Wistar rats, the objective of the present study was to determine if there is natural dendritic remodeling in the female Wistar rat throughout the estrous cycle. This study analyzed the dendritic arborization of pyramidal neurons CA1 and CA3 of the dorsal hippocampus in each phase of the estrous cycle. We used the Golgi-Cox staining method and Sholl analysis to evaluate the dendritic length and density of dendritic spines. Our results showed that the dendritic length of the basilar and apical trees of CA1 neurons was longer in the metestrus phase. In CA3 neurons, only the apical dendritic trees showed longer dendritic length during metestrus. There was no variation in the density of dendritic spines in relation to any of the phases of the estrous cycle. Taken together, these results indicated that pyramidal neurons of the CA1 and CA3 regions of the dorsal hippocampus in the Wistar rat exhibited changes in dendritic length in the metestrus phase of the estrous cycle. Together, these data are important when considering the use of these organisms in behavioral studies.

Ligand-Gated Purinergic Receptors Regulate HIV-1 Tat and Morphine Related Neurotoxicity in Primary Mouse Striatal Neuron-Glia Co-Cultures

Emerging evidence suggests that opioid drugs, such as morphine and heroin, can exacerbate neuroAIDS. Microglia are the principal neuroimmune effectors thought to be responsible for neuron damage in HIV-infected individuals, and evidence suggests that opioid drugs acting via μ opioid receptors in microglia aggravate the neuropathophysiological effects of HIV. Key aspects of microglial function are regulated by the P2X family of ATP activated ligand-gated ion channels. In addition, opioid-dependent microglial activation has been reported to be mediated through P2X4 signaling, which prompted us to investigate whether the cation-permeable P2X receptors contribute to the neurotoxic effects of HIV and morphine. To address this question, neuron survival, as well as other endpoints including changes in dendritic length, extracellular ATP levels, and intracellular calcium levels, were assayed in primary neuron-glia co-cultures from mouse striatum. Treatment with TNP-ATP, a non-selective P2X antagonist, prevented the neurotoxic effects of exposure to morphine and/or HIV Tat, or ATP alone, suggesting P2X receptors mediate the neurotoxic effects of these insults in striatal neurons. Although P2X7, and perhaps P2X1, receptor activation decreases neuron survival, neither P2X1, P2X3, nor P2X7 selective receptor antagonists prevented Tat and/or morphine-induced neurotoxicity. These and other experiments indicate the P2X receptor family contributes to Tat- and morphine- related neuronal injury, and provide circumstantial evidence implicating P2X4 receptors in particular. Our findings reveal that members of the P2X receptor family, especially P2X4, may be novel therapeutic targets for restricting the synaptodendritic injury and neurodegeneration that accompanies neuroAIDS and opiate abuse.

Absence of Large-Scale Dendritic Plasticity of Layer 5 Pyramidal Neurons in Peri-Infarct Cortex

When stroke or traumatic brain injury lead to cortical damage, how do surviving neurons rewire the brain to restore lost functionalities? Several Golgi studies have argued for de novo growth and branching of dendrites of pyramidal neurons in the spared hemisphere, but the results could not always be replicated. Functional brain imaging studies in humans and rodents suggest that significant neuronal plasticity occurs in areas surrounding the cortical lesion, but whether dendritic rearrangements occur there has been less well studied, especially after stroke. We used in vivo two-photon microscopy in adult mice expressing green fluorescent protein to monitor longitudinally the length and branch complexity of entire apical dendritic arbors from layer 5 pyramidal neurons distributed over a large peri-infarct cortex region after middle cerebral artery occlusion. We find no evidence of growth of dendrites or addition of new branches to their arbors over a period of 3 months after stroke. Instead, we observed a two-step pruning process: an initial decrease in dendritic length, followed by a loss of dendritic branches. Importantly, the shortening of branch tips reflected a general shrinkage in the dendritic apical tree, suggesting that mechanical forces attributable to the involution of the infarct contributed to the changes in dendritic length. These results help resolve a long-standing debate regarding the role of large-scale dendritic plasticity of pyramidal neurons in functional recovery after cortical injury.

Changes in dendritic morphology and spine density in motor cortex of the adult rat after stroke during infancy

Cognitive and motor deficits are pervasive in children that suffer early brain injury. The aim of this study was to determine the impact that early damage has on dendritic spine density and other aspects of dendritic morphology of neurons in the motor cortex. Also of interest was how changes in dendritic structure evolved across the lifespan. Ischemia was induced in 10-day-old Long Evans rats by injection of Rose Bengal dye and a laser positioned over right motor cortex. Animals were sacrificed at two and six months of age, and brains were processed for Golgi-Cox staining. Animals exposed to early damage exhibited increases in length of basilar dendrites at two months of age, however no differences in spine density were found across groups at this age. At six months of age, injured animals demonstrated an overall decrease in apical and basilar spine density. Our results suggest that the changes in dendritic length and spine density observed after early damage are unable to be maintained as the animal ages. The observation that increases in spine density do not necessarily coincide with increases in dendritic length suggests that the two processes may not be dependent on one another and suggest two independent plasticity processes responding to damage.

Effect of the environment on the dendritic morphology of the rat auditory cortex

The present study aimed to identify morphological correlates of environment-induced changes at excitatory synapses of the primary auditory cortex (A1). We used the Golgi-Cox stain technique to compare pyramidal cells dendritic properties of Sprague-Dawley rats exposed to different environmental manipulations. Sholl analysis, dendritic length measures, and spine density counts were used to monitor the effects of sensory deafness and an auditory version of environmental enrichment (EE). We found that deafness decreased apical dendritic length leaving basal dendritic length unchanged, whereas EE selectively increased basal dendritic length without changing apical dendritic length. On the contrary, deafness decreased while EE increased spine density in both basal and apical dendrites of A1 Layer 2/3 (LII/III) neurons. To determine whether stress contributed to the observed morphological changes in A1, we studied neural morphology in a restraint-induced model that lacked behaviorally relevant acoustic cues. We found that stress selectively decreased apical dendritic length in the auditory but not in the visual primary cortex. Similar to the acoustic manipulation, stress-induced changes in dendritic length possessed a layer-specific pattern displaying LII/III neurons from stressed animals with normal apical dendrites but shorter basal dendrites, while infragranular neurons (Layers V and VI) displayed shorter apical dendrites but normal basal dendrites. The same treatment did not induce similar changes in the visual cortex, demonstrating that the auditory cortex is an exquisitely sensitive target of neocortical plasticity, and that prolonged exposure to different acoustic as well as emotional environmental manipulation may produce specific changes in dendritic shape and spine density.

Alterations in dendritic morphology of the prefrontal cortical and striatum neurons in the unilateral 6‐OHDA‐rat model of Parkinson's disease

We have studied the morphological changes of the dendrites of the pyramidal neurons of the prefrontal cortex (PFC) and the medium spiny neurons of the caudate-putamen (CPu) and nucleus accumbens (NAcc) induced by the injection of 6-hydroxydopamine (6-OHDA) into the substantia nigra pars compacta (SNc). The unilateral 6-OHDA-induced lesion of the SNc was made in Wistar rats to produce the Parkinson model lesion. Two weeks after the injection, the testing of rotational behavior caused by amphetamine injection was done to assess the animals with lesions. Four weeks after the 6-OHDA injection, the morphology of the pyramidal cells of Layer 5 of the PFC and the medium spiny neurons of the CPu and NAcc were quantified by modified Golgi-Cox staining. The results showed that the length of dendrites, the branching, and the density of dendritic spines on the medium spiny neurons of the same side of the caudate-putamen lesion were significantly decreased in rats with the unilateral 6-OHDA-induced lesion of the SNc. The pyramidal neurons of the PFC and medium spiny neurons of the NAcc showed a decrease in the density of dendritic spines without significant changes in dendritic length or arborization. Our data suggest that the SNc lesion with the 6-OHDA, Hemiparkinsonism animal model may lead to altered neuronal plasticity in the CPu, NAcc, and PFC that may have participated in the emergence of the behavioral changes observed in these animals.

Alterations in dendritic morphology of prefrontal cortical and nucleus accumbens neurons in post-pubertal rats after neonatal excitotoxic lesions of the ventral hippocampus

Neonatal ventral hippocampal (nVH) lesions in rats result in adult onset of a number of behavioral and cognitive abnormalities analogous to those seen in schizophrenia, including hyperresponsiveness to stress and psychostimulants and deficits in working memory, sensorimotor gating and social interaction. Molecular and neurochemical alterations in the prefrontal cortex (PFC) and nucleus accumbens (NAcc) of nVH-lesioned animals suggest developmental reorganization of these structures following neonatal lesions. To determine whether nVH lesions lead to neuronal morphological changes, we investigated the effect of nVH lesion on dendritic structure and spine density of pyramidal neurons of the PFC and medium spiny neurons of the NAcc. Bilateral ibotenic acid-induced lesion of the VH was made in Sprague-Dawley pups at postnatal day 7 (P7); and at P70, neuronal morphology was quantified by modified Golgi-Cox staining. The results show that length of basilar dendrites and branching and the density of dendritic spines on layer 3 pyramidal neurons were significantly decreased in rats with nVH lesions. Medium spiny neurons from the NAcc showed a decrease in the density of dendritic spines without significant changes in dendritic length or arborization. The data, comparable to those observed in the PFC of schizophrenic patients, suggest that developmental loss of excitatory projections from the VH may lead to altered neuronal plasticity in the PFC and the NAcc that may contribute to the behavioral changes in these animals.

Cortical distribution of neurofibrillary tangles in alzheimer's disease matches the pattern of neurons that retain their capacity of plastic remodelling in the adult brain

The formation of neurofibrillary tangles in Alzheimer's disease shows a preferential involvement of certain cytoarchitecturally defined cortical areas suggesting systematic differences in regional neuronal vulnerability. The cellular and molecular nature of this selective neuronal vulnerability that follows a certain hierarchy of structural brain organization is largely unknown. In the present study, we compared the regional pattern of tangle density in Alzheimer's disease with systematic regional differences in neuronal plasticity that can be observed both during ageing and in Alzheimer's disease. Changes in dendritic length and arborization of Golgi-impregnated pyramidal neurons were analysed after three-dimensional reconstruction in 12 cortical areas. The intensity of dendritic remodelling that was observed during ageing as well as in Alzheimer's disease was regionally different and decreased in the following order: transentorhinal region >limbic areas (entorhinal region, hippocampus)>non-primary association areas (37, 40, 46)>primary sensory association areas (7, 18, 22)>primary sensory and motor cortex (17, 41, 4). These regional differences of neuronal plasticity follow the same pattern as the regional vulnerability to tangle formation in Alzheimer's disease. The results of the present study provide evidence that a high degree of structural neuronal plasticity might predispose neurons to tangle formation.

Effect of beta amyloid peptides on neurons in hippocampal slice cultures

Several investigators have described the neurotrophic and neurotoxic effects of beta amyloid peptide fragments on dissociated hippocampal neurons in culture. In these prior studies, the peptides were added to dissociated cultures between day 0 and day 4 in vitro, before hippocampal neurons are fully mature. We have analyzed the neurotrophic and neurotoxic effects of beta amyloid fragments β1–28, β25–35 and β1–40 on hippocampal slice cultures, whose physiology and morphology resembles the intact hippocampus. Addition of β1–28 or β25–35 to the growth medium did not produce significant changes in dendritic length or number of branches. Nerve growth factor, previously reported to enhance the neurotoxic effects of β1–40 on dissociated hippocampal neurons in culture, did not significantly enhance the neurotrophic effects of β1–128. To achieve high local concentrations of peptides and to avoid potential access problems in the cultures, we injected β1–28, β25–35, and β1–40 directly into the cultures. Amyloid-mediated neurotoxicity was not observed for β1–28 or β25–35, but β1–40 appeared to produce neurodegeneration around the site of injection.

Differentiation of granule cell dendrites in the dentate gyrus of the rhesus monkey: a quantitative Golgi study.

The differentiation of granule cell dendrites in the dentate gyrus of the hippocampal region was studied in a series of developing fetal and postnatal rhesus monkeys whose brains were processed by the rapid Golgi method. The total combined lengths of dendrites, the total number of dendritic spines, and their density on the proximal, middle, and distal thirds of the dendritic shafts were determined at embryonic days 58, 95, 120, 153, term (165), postnatal days 3, 20, 60, 150, 365, and adults. At all ages examined, granule cells exhibited various levels of maturation with the more differentiated cells being situated in the superficial strata of the granular layer and the less mature cells lying in progressively deeper positions, thus conforming to the outside-to-inside spatiotemporal gradient of their genesis. Quantitative analysis shows that, in this primate, hippocampal granule cells differentiate mainly in the second half of gestation with all measured parameters attaining mature values by the time of birth. However, the analysis also reveals a transient phase of exuberant postnatal development which involves excessive dendritic branching, regional changes in dendritic length, overproduction of dendritic spines, and redistribution of spines within the molecular layer. After reaching peak values around the middle of the first year of life, these parameters decrease and in adult monkeys fall back to the neonatal level.

The development of pyramidal neurons after eye opening in the visual cortex of hooded rats: A quantitative study

Dendritic maturation of pyramidal neurons in layers III and V of the rat visual cortex was quantified in rapid Golgi-stained tissue from socially housed hooded rats at ages 15, 30, and 60 days. A complex pattern of changes emerged. Dendritic branching analyses revealed that in layer III both bifurcating and terminal basilar branches increased in length over the sampled days. Likewise, total dendritic length increased in the layer III basilar dendritic tree between 15 and 30 days of age and peaked at 30 days of age in the layer III apical oblique branches. No changes in dendritic length were observed in layer V pyramidal neurons. Neither layer III nor layer V neurons exhibited any changes in the number of basilar or apical oblique branches over the time period studied. Dendritic spine density increased on terminal basilar branches in both cell populations between 15 and 30 days. There also was an increase in spine density on the layer V pyramidal apical shaft between 15 and 30 days, while on layer III bifurcating basilar branches, spine density fell between 30 and 60 days. These data indicate that while dendrites may continue to grow longer, pyramidal neurons do not on average generate additional branches after day 15. However, the pattern of spine density is still changing between 15 and 60 days of age. Thus no single developmental pattern holds for all cell populations or even across areas of the dendritic field within a population.