Dendritic Trees Of Pyramidal Cells Research Articles

Modeling the effect of dendritic input location on MEG and EEG source dipoles.

The cerebral sources of magneto- and electroencephalography (MEG, EEG) signals can be represented by current dipoles. We used computational modeling of realistically shaped passive-membrane dendritic trees of pyramidal cells from the human cerebral cortex to examine how the spatial distribution of the synaptic inputs affects the current dipole. The magnitude of the total dipole moment vector was found to be proportional to the vertical location of the synaptic input. The dipole moment had opposite directions for inputs above and below a reversal point located near the soma. Inclusion of shunting-type inhibition either suppressed or enhanced the current dipole, depending on whether the excitatory and inhibitory synapses were on the same or opposite side of the reversal point. Relating the properties of the macroscopic current dipoles to dendritic current distributions can help to provide means for interpreting MEG and EEG data in terms of synaptic connection patterns within cortical areas.

Pyramidal cells in V1 of African rodents are bigger, more branched and more spiny than those in primates

Pyramidal cells are characterized by markedly different sized dendritic trees, branching patterns, and spine density across the cortical mantle. Moreover, pyramidal cells have been shown to differ in structure among homologous cortical areas in different species; however, most of these studies have been conducted in primates. Whilst pyramidal cells have been quantified in a few cortical areas in some other species there are, as yet, no uniform comparative data on pyramidal cell structure in a homologous cortical area among species in different Orders. Here we studied layer III pyramidal cells in V1 of three species of rodents, the greater cane rat, highveld gerbil, and four-striped mouse, by the same methodology used to sample data from layer III pyramidal cells in primates. The data reveal markedly different trends between rodents and primates: there is an appreciable increase in the size, branching complexity, and number of spines in the dendritic trees of pyramidal cells with increasing size of V1 in the brain in rodents, whereas there is relatively little difference in primates. Moreover, pyramidal cells in rodents are larger, more branched and more spinous than those in primates. For example, the dendritic trees of pyramidal cells in V1 of the adult cane rat are nearly three times larger, and have more than 10 times the number of spines in their basal dendritic trees, than those in V1 of the adult macaque (7900 and 600, respectively), which has a V1 40 times the size that of the cane rat. It remains to be determined to what extent these differences may result from development or reflect evolutionary and/or processing specializations.

Spinogenesis and Pruning in the Anterior Ventral Inferotemporal Cortex of the Macaque Monkey: An Intracellular Injection Study of Layer III Pyramidal Cells

Pyramidal cells grow and mature at different rates among different cortical areas in the macaque monkey. In particular, differences across the areas have been reported in both the timing and magnitude of growth, branching, spinogenesis, and pruning in the basal dendritic trees of cells in layer III. Presently available data suggest that these different growth profiles reflect the type of functions performed by these cells in the adult brain. However, to date, studies have focused on only a relatively few cortical areas. In the present investigation we quantified the growth of the dendritic trees of layer III pyramidal cells in the anterior ventral portion of cytoarchitectonic area TE (TEav) to better comprehend developmental trends in the cerebral cortex. We quantified the growth and branching of the dendrities, and spinogenesis and pruning of spines, from post-natal day 2 (PND2) to four and a half years of age. We found that the dendritic trees increase in size from PND2 to 7 months of age and thereafter became smaller. The dendritic trees became increasingly more branched from PND2 into adulthood. There was a two-fold increase in the number of spines in the basal dendritic trees of pyramidal cells from PND2 to 3.5 months of age and then a 10% net decrease in spine number into adulthood. Thus, the growth profile of layer III pyramidal cells in the anterior ventral portion of the inferotemporal cortex differs to that in other cortical areas associated with visual processing.

GABA-ERGIC DYSFUNCTION IN SCHIZOPHRENIA: FROM POSTMORTEM STUDIES TO ANIMAL MODELS

Nine years have passed since the first postmortem DNA microarray studies of schizophrenia were published, and it appears that this technologyhas generated several important leads that continue to shape translational neuroscience studies investigating the cellular/molecular bases of schizophrenia. Specifically, independently replicated expression profiling studies of the prefrontal cortex in schizophrenia revealed abnormalities in expression of genes encoding 1) synaptic proteins, 2) proteins related to GABA signaling, 3) immune/chaperone system proteins, 4) metabolic pathway components and 5) oligodendrocyterelated proteins. The GABA-ergic systemic dysfunction is perhaps the most consistently observed deficit associated with schizophrenia. At a molecular level, the PFC of humans with schizophrenia is characterized by an interrelated transcript deficit that consists of downregulation of BDNF, TRKB, GAD67, SST, NPY, PARV, CCK and GABRAD genes, clearly implicating the cortical GABAergic interneuron as a central component of the pathophysiology underlying the disease. Of these, reduction of the transcript encoding glutamic acid decarboxylase 67 kDa (GAD67) is the most robust and consistently replicated finding across different cohorts. GAD67, the critical GABA synthesis enzyme in the brain, is downregulated in distinct interneuron populations of the human cortex. Each of these affected cell types mediate a different kind of inhibition: 1) a chandelier-cell subpopulationof parvalbumin (PARV)-GAD67neurons is responsible for regulating the output of projection neurons at the axon initial segment, 2) small basket andMartinotti cells containingGAD67+ CALB+SST(±NPY) are responsible for the inhibition of the distal dendritic tree of pyramidal cells, and 3) GAD67+CALR(±CCK) interneurons regulate both the dendritic inputs of pyramidal cells as well as provide input to other GABAergic neurons. To understand the GABAergic dysfunction in schizophreniawemust develop animalmodels that modulate gene expression in a phenotypic and regional fashion. Therefore, we hypothesized that transgenic mouse models directed to cortical downregulation of GAD67 in distinct interneuron subtypes should both mimic the molecular and cellular human postmortem findings in schizophrenia, and have distinct consequences on cortical functioning. To test this hypothesis, we developed a novel BAC-driven transgenic mice system that is capable of cell-type specific transcript downregulation using an endogenous miRNA processing cellular mechanism. We generated several transgenic mice lines with cell-type specific downregulation of GAD67 protein in theNPY+, CCK+and PV+ interneurons using exon-embedded miRNA. This transgenic approach allowed us rapid, cell type-specific in vivo downregulation of the transcripts of interest (reduction of GAD67 in specific interneuronal subpopulations), avoiding the labor-intensive and resource-demanding generation of conditional knockout animals. These animal models will allow us to gain a critical understanding of the mechanisms underlying cortical inhibition and the anatomical and behavioral consequences of disturbing this network. Furthermore, the mice generated in this proposal may be useful for testing current lead compounds with therapeutic indications for symptoms of schizophrenia, and aid in the knowledge-based development of drugs for this devastating disease.

Activation Conditions for the Induction of Metabotropic Glutamate Receptor-Dependent Long-Term Depression in Hippocampal CA1 Pyramidal Cells

Two forms of homosynaptic long-term depression (LTD) are distinguished in hippocampal CA1 pyramidal cells, one which is NMDA receptor dependent and the other metabotropic glutamate receptor (mGluR) dependent. Although the molecular processes involved in mGluR-LTD are well characterized, the conditions of circuit activation required for its induction remain unclear. We show that mGluR-LTD cannot be induced in synaptically coupled CA3-CA1 pyramidal cell pairs. Experiments to address the underlying mechanisms indicate that, even when glutamate transporters are blocked, one presynaptic cell releases insufficient glutamate to evoke an mGluR-mediated current in a connected CA1 cell. These findings imply that extrasynaptic diffusion is not a limiting factor and are consistent with a sparse distribution of functional mGluRs in the dendritic tree of pyramidal cells. Thus, the discharge of multiple Schaffer collaterals to a targeted cell is necessary for mGluR-LTD. Our experiments indicate that approximately eight CA3 inputs to a CA1 pyramidal cell must be activated to induce mGluR-LTD.

Spinogenesis and pruning in the primary auditory cortex of the macaque monkey ( Macaca fascicularis): An intracellular injection study of layer III pyramidal cells

Recently we demonstrated that neocortical pyramidal cells in visual, visual association and prefrontal cortex of the macaque monkey are characterised by different growth, branching, spinogenesis and pruning during development. Some neurons, such as those in the primary visual area, prune more spines than they grow following sensory onset, while others such as those in area TE grow more than they prune. To what extent these different neuronal growth profiles may vary among cortical areas remains to be determined. To better comprehend the nature and extent of these regional differences in pyramidal cell growth profiles we expanded the bases for comparison by studying neurons in the primary auditory cortex (A1). We found that pyramidal cells in A1 continue to grow their basal dendritic trees beyond the peak period of spinogenesis (3 1/ 2 months) up until at least 7 months of age. Likewise, the most prolific branching patterns were observed in the dendritic trees of pyramidal cells at 7 months of age. These data reveal that the basal dendritic trees of cells in A1 continue to grow for a much longer period, and attain almost double the number of spines, as compared with those in V1. Such differences in the growth profiles of neocortical pyramidal cells among cortical areas may influence therapeutic outcomes when applying new technologies such as neurotrophic delivery devices or stem cell therapy.

Spinogenesis and Pruning Scales across Functional Hierarchies

Spinogenesis and synaptic pruning during development are widely believed to subserve connectional specificity in the mature CNS via Hebbian-type reinforcement. Refinement of neuronal circuit through this "use it or lose it" principle is considered critical for brain development. Here we demonstrate that the magnitude of spinogenesis and pruning in the basal dendritic trees of pyramidal cells differ dramatically among sensory, association, and executive cortex. Moreover, somewhat counterintuitively, we demonstrate that the dendritic trees of pyramidal cells in the primary visual area actually lose more spines than they grow following the onset of visual experience. The present findings reveal that the process of synaptic refinement differs not only according to time, but also location.

Spike propagation in dendrites with stochastic ion channels

We investigate the effects of the stochastic nature of ion channels on the faithfulness, precision and reproducibility of electrical signal transmission in weakly active, dendritic membrane under in vitro conditions. The properties of forward and backpropagating action potentials (BPAPs) in the dendritic tree of pyramidal cells are the subject of intense empirical work and theoretical speculation (Larkum et al., 1999; Zhu, 2000; Larkum et al., 2001; Larkum and Zhu, 2002; Schaefer et al., 2003; Williams, 2004; Waters et al., 2005). We numerically simulate the effects of stochastic ion channels on the forward and backward propagation of dendritic spikes in Monte-Carlo simulations on a reconstructed layer 5 pyramidal neuron. We report that in most instances there is little variation in timing or amplitude for a single BPAP, while variable backpropagation can occur for trains of action potentials. Additionally, we find that the generation and forward propagation of dendritic Ca(2+) spikes are susceptible to channel variability. This indicates limitations on computations that depend on the precise timing of Ca(2+) spikes.

Pyramidal cell specialization in the occipitotemporal cortex of the Chacma baboon (Papio ursinus)

Pyramidal cell structure varies systematically in occipitotemporal visual areas in monkeys. The dendritic trees of pyramidal cells, on average, become larger, more branched and more spinous with progression from the primary visual area (V1) to the second visual area (V2), the fourth (V4, or dorsolateral DL visual area) and inferotemporal (IT) cortex. Presently available data reveal that the extent of this increase in complexity parallels the expansion of occipitotemporal cortex. Here we extend the basis for comparison by studying pyramidal cell structure in occipitotemporal cortical areas in the chacma baboon. We found a systematic increase in the size of and branching complexity in the basal dendritic trees, as well as a progressive increase in the spine density along the basal dendrites of layer III pyramidal cells through V1, V2 and V4. These data suggest that the trend for more complex pyramidal cells with anterior progression through occipitotemporal visual areas is not a feature restricted to monkeys and prosimians, but is a widespread feature of occipitotemporal cortex in primates.

Specialization in pyramidal cell structure in the sensory‐motor cortex of the Chacma baboon (Papio ursinus) with comparative notes on macaque and vervet monkeys

The systematic study of pyramidal cell structure has revealed new insights into specialization of the phenotype in the primate cerebral cortex. Regional specialization in the neuronal phenotype may influence patterns of connectivity and the computational abilities of the circuits they compose. The comparative study of pyramidal cells in homologous cortical areas is beginning to yield data on the evolution and development of such specialized circuitry in the primate cerebral cortex. Recently, we have focused our efforts on sensory-motor cortex. Based on our intracellular injection methodology, we have demonstrated a progressive increase in the size of, the branching structure in, and the spine density of the basal dendritic trees of pyramidal cells through somatosensory areas 3b, 1, 2, 5, and 7 in the macaque and vervet monkeys. In addition, we have shown that pyramidal cells in premotor area 6 are larger, more branched, and more spinous than those in the primary motor cortex (MI or area 4) in the macaque monkey, vervet monkey, and baboon. Here we expand the basis for comparison by studying the basal dendritic trees of layer III pyramidal cells in these same sensory-motor areas in the chacma baboon. The baboon was selected because it has a larger cerebral cortex than either the macaque or vervet monkeys; motor cortex has expanded disproportionately in these three species; and motor cortex in the baboon reportedly has differentiated to include a new cortical area not present in either the macaque or vervet monkeys. We found, as in monkeys, a progressive increase in the morphological complexity of pyramidal cells through areas 3b, 5, and 7, as well as from area 4 to area 6, suggesting that areal specialization in microcircuitry was likely to be present in a common ancestor of primates. In addition, we found subtle differences in the extent of the interareal differences in pyramidal cell structure between homologous cortical areas in the three species.

A quantitative analysis of the dendritic organization of pyramidal cells in the rat hippocampus.

The three dimensional organization of the dendritic trees of pyramidal cells in the rat hippocampus was investigated using intracellular injection of horseradish peroxidase in the in vitro hippocampal slice preparation and computer-aided reconstruction. The total dendritic length, dendritic length in each of the hippocampal laminae, and the number of dendritic branches were measured in 20 CA1 pyramidal cells, 7 neurons in CA2 and 20 CA3 pyramidal cells. The total dendritic length of CA3 pyramidal cells varied in a consistent fashion depending on their position within the field. Cells located close to the dentate gyrus had the smallest dendritic trees which averaged 9,300 microns in total length. Cells in the distal part of CA3 (near CA2) had the largest dendritic trees, averaging 15,800 microns. The CA2 field contained cells which resembled CA3 pyramidal cells in most respects except for the absence of thorny excrescences on their proximal dendrites. There were also smaller pyramidal cells that resembled CA1 neurons. CA1 pyramidal cells tended to be more homogeneous. Pyramidal neurons throughout the transverse extent of CA1 had a total dendritic length on the order of 13,500 microns. The quantitative analysis of the laminar distribution of dendrites demonstrated that the stratum oriens and stratum radiatum contained significant portions of the pyramidal cell dendritic trees. In Ca3, for example, 42-51% of the total dendritic length was located in stratum oriens; about 34% of the dendritic tree was located in stratum radiatium. The amount of dendritic length in stratum lacunosum-moleculare of CA3 varied depending on the location of the cell. Many CA3 cells located within the limbs of the dentate gyrus, for example, had no dendrites extending into stratum lacunosum-moleculare whereas those located distally in CA3 had about the same percentage of their dendritic tree in stratum lacunosum-moleculare as in stratum radiatum. In CA1, nearly half of the dendritic length was located in stratum radiatum, 34% was in stratum oriens and 18% was in stratum lacunosum-moleculare. These studies identified distinctive dendritic branching patterns, in the stratum radiatum and stratum lacunosum-moleculare, which clearly distinguished CA3 from CA1 neurons.

The physiology and morphology of two types of electrosensory neurons in the weakly electric fishApteronotus leptorhynchus

Previous anatomical and physiological studies of the gymnotoid electrosensory lateral line lobe (ELLL) suggest that the anatomically identified basilar and non-basilar pyramidal cells correspond to the physiologically defined E and I cells. Intracellular injection of horseradish peroxidase (HRP) into physiologically identified E and I cells confirms this hypothesis. The morphologies and physiological responses of the basilar and non-basilar pyramidal cells were compared. Both types of pyramidal cells have extensive apical dendritic trees that interact with a parallel fiber network in the ELLL. The apical dendritic trees of the non-basilar pyramidal cells have a wider spread along the rostrocaudal axis of the ELLL than those of the basilar pyramidal cells. This difference is discussed in reference to the interaction of these cell types with the parallel fibers of the ELLL. The density of apical dendritic branches was measured and related to the distance of these branches from the cell body. No obvious differences were seen between the dendritic density patterns of basilar and non-basilar pyramidal cells. An interesting correlation, however, exists between the atypical physiological characteristics of two basilar pyramidal cells and their dendritic density patterns. Two cells of the medial (ampullary) segment of the ELLL were analyzed. Like the pyramidal cells of the three lateral (tuberous) regions of the ELLL, the physiology of these cells appears to be related to the presence of an extended basilar process. The ampullary cells, however, have apical dendritic trees that are oriented orthogonally to the dendritic trees of the pyramidal cells.

Effects of differential environments on plasticity of dendrites of cortical pyramidal neurons in adult rats

Thickening of the frontal cortex and especially the occipital cortex was observed in adult rats after exposure to the “enriched” condition. An increase in branching and in length of terminal segments was found in the dendritic tree of pyramidal cells in layers II and III of the visual cortex of the adult rat after exposure to “standard” and enriched conditions. These exposures began at day 112 and continued 30 days. The increase observed in the basal dendritic tree of pyramidal cells in the superficial layers was significantly greater in the enriched conditions than in the standard condition. It appeared, furthermore, that branching occurred predominantly on basal terminal segments of all orders at a considerable distance from the tip. This mode of growth is similar to that observed in the cortex of normal immature rats. The differential conditions did not influence the bifurcation angles. The dendritic and cortical changes and changes reported in the literature indicate that the effects of differential experience are not limited to a short, “critical” period.