Dendritic spinules detected by the peroxidase method]

The structure of marked associative pyramidal neurons, their dendrites, and spines in layer III of somato-sensory cortex in cats after HRP-injection into the motor cortex has been described. Secondary and tertiary branches of basal dendrites are revealed more often than the apical ones. But the spines, especially their heads, were more obvious on the apical dendrites. The marked associative neurons are displaced sparsely, making no accumulations.     

Neural recognition molecules CHL1 and NB-3 regulate apical dendrite orientation in the neocortex via PTP alpha

Apical dendrites of pyramidal neurons in the neocortex have a stereotypic orientation that is important for neuronal function. Neural recognition molecule Close Homolog of L1 (CHL1) has been shown to regulate oriented growth of apical dendrites in the mouse caudal cortex. Here we show that CHL1 directly associates with NB-3, a member of the F3/contactin family of neural recognition molecules, and enhances its cell surface expression. Similar to CHL1, NB-3 exhibits high-caudal to low-rostral expression in the deep layer neurons of the neocortex. NB-3-deficient mice show abnormal apical dendrite projections of deep layer pyramidal neurons in the visual cortex. Both CHL1 and NB-3 interact with protein tyrosine phosphatase alpha (PTPalpha) and regulate its activity. Moreover, deep layer pyramidal neurons of PTPalpha-deficient mice develop misoriented, even inverted, apical dendrites. We propose a signaling complex in which PTPalpha mediates CHL1 and NB-3-regulated apical dendrite projection in the developing caudal cortex.     

Ontogeny of the mouse motor cortex. The polymorph layer or layer VI. A Golgi and electronmicroscopical study

Summary The development of neurons and their synapses of the mouse motor cortex has been studied from the first postnatal day up to an age of three weeks both electronmicroscopically and with the Golgi method. Special attention has been paid to the maturation of the different cell types in the sixth cortical layer and their dendritic organization within this layer.The polymorph layer is subdivided into two zones: an internal (VIb) and an external one (VIa). In these zones six different cell types can be identified both electronmicroscopically and with the Golgi method: large, small and inverted pyramidal cells in VIa; horizontal cells, star cells and small pyramidal cells in VIb.Spines of apical dendrites of large pyramidal cells in sublayer VIa can be detected as early as the 6th postnatal day. About the ninth day the basal dendrites as well show emerging spines. Somatic spines are found only on the large pyramidal cells and disappear slowly towards the end of the 3rd postnatal week.The small pyramidal cells show developing spines on their apical dendrite in the first half of the second postnatal week. The final density and distribution of spines is reached by the stem dendrites towards the end of the second week, by the basal dendrites during the third week. The maturation process of the improperly orientated neurons occurs in time in between the large and the small pyramidal cells.The axo-somatic synapses appear in general at a later date than the axo-dendritic ones. In the horizontal cells axo-somatic synapses are visible already at the seventh postnatal day.At the end of the first week especially in layer VIb many immature neurons with an ovoid or round nucleus are present having little if any endoplasmic reticulum organised as ergastoplasm.Towards the end of the second week however most neurons in the polymorph layer have a well developed endoplasmic reticulum.Electronmicroscopical pictures reveal in outgrowing dendrites many enlargements filled with vesicles, these correspond to the varicosities seen in Golgi pictures. At nine days postnatally the first myelinated fibres appear.Aided by grant (R-209-67) from the United Cerebral Palsy Research and Educational Foundation, New York.     

Cholinergic pyramidal neurons of the motor region of human neocortex

By means of histochemical methods for revealing +choline acetyltransferase (ChAT) and acetylcholinesterase (AChE) cytoarchitectonic of the field 4 of the motor cortex of the cerebrum has been studied in 5 persons at the age of 33-65 years. An essential part of neurons at revealing AChE and most of them at revealing ChAT do not react. Among giant pyramidal neurons (Bets) according to ChAT activity, 4 types are distinguished: neurons with low, middle, high and very high activity. The presence of ChAT is ascertained in middle and large pyramidal neurons of the III layer. Presence of ChAT-positive synapses is demonstrated in apical dendrites. A conclusion is made that less part of the pyramidal in the III, V layers are cholinergic ones.     

Regulation of back-propagating action potentials in hippocampal neurons.

Protein kinase C has recently been shown to modulate the slow recovery from inactivation of Na+ channels in apical dendrites of hippocampal CA1 pyramidal neurons. Moreover, dendritic, A-type K+ channels have been found to be modulated by protein kinases A and C and by mitogen-activated protein kinase. The electrical signalling ability of these dendrites is thus highly regulated by a number of neurotransmitters and second-messenger systems.     

Phosphorylation of CRMP2 is involved in proper bifurcation of the apical dendrite of hippocampal CA1 pyramidal neurons

The neural circuit in the hippocampus is important for higher brain functions. Dendrites of CA1 pyramidal neurons mainly receive input from the axons of CA3 pyramidal neurons in this neural circuit. A CA1 pyramidal neuron has a single apical dendrite and multiple basal dendrites. In wild‐type mice, most of CA1 pyramidal neurons extend a single trunk, or alternatively, the apical dendrite bifurcates into two daughter trunks at the stratum radiatum layer. We previously reported the proximal bifurcation phenotype in Sema3A?/?, p35?/?, and CRMP4?/? mice. Cdk5/p35 phosphorylates CRMP2 at Ser522, and inhibition of this phosphorylation suppressed Sema3A‐induced growth cone collapse. In this study, we analyzed the bifurcation points of the apical dendrites of hippocampal CA1 pyramidal neurons in CRMP2KI/KI mice in which the Cdk5/p35‐phosphorylation site Ser522 was mutated into an Ala residue. The proximal bifurcation phenotype was not observed in CRMP2KI/KI mice; however, severe proximal bifurcation of apical dendrites was found in CRMP2KI/KI;CRMP4?/? mice. Cultured hippocampal neurons from CRMP2KI/KI and CRMP2KI/KI;CRMP4?/? embryos showed an increased number of dendritic branching points compared to those from wild‐type embryos. Sema3A increased the number of branching points and the total length of dendrites in wild‐type hippocampal neurons, but these effects of Sema3A for dendrites were notobserved in CRMP2KI/KI and CRMP2KI/KI;CRMP4?/?hippocampal neurons. Binding of CRMP2 to tubulin increased in both CRMP2KI/KI and CRMP2KI/KI:CRMP4?/? brain lysates. These results suggest that CRMP2 and CRMP4 synergistically regulate dendritic development, and CRMP2 phosphorylation is critical for proper bifurcation of apical dendrite of CA1 pyramidal neurons. © 2012 Wiley Periodicals, Inc. Develop Neurobiol, 2013     

Computational simulation of the input-output relationship in hippocampal pyramidal cells

The precise mapping of how complex patterns of synaptic inputs are integrated into specific patterns of spiking output is an essential step in the characterization of the cellular basis of network dynamics and function. Relative to other principal neurons of the hippocampus, the electrophysiology of CA1 pyramidal cells has been extensively investigated. Yet, the precise input-output relationship is to date unknown even for this neuronal class. CA1 pyramidal neurons receive laminated excitatory inputs from three distinct pathways: recurrent CA1 collaterals on basal dendrites, CA3 Schaffer collaterals, mostly on oblique and proximal apical dendrites, and entorhinal perforant pathway on distal apical dendrites. We implemented detailed computer simulations of pyramidal cell electrophysiology based on three-dimensional anatomical reconstructions and compartmental models of available biophysical properties from the experimental literature. To investigate the effect of synaptic input on axosomatic firing, we stochastically distributed a realistic number of excitatory synapses in each of the three dendritic layers. We then recorded the spiking response to different stimulation patterns. For all dendritic layers, synchronous stimuli resulted in trains of spiking output and a linear relationship between input and output firing frequencies. In contrast, asynchronous stimuli evoked non-bursting spike patterns and the corresponding firing frequency input-output function was logarithmic. The regular/irregular nature of the input synaptic intervals was only reflected in the regularity of output inter-burst intervals in response to synchronous stimulation, and never affected firing frequency. Synaptic stimulations in the basal and proximal apical trees across individual neuronal morphologies yielded remarkably similar input-output relationships. Results were also robust with respect to the detailed distributions of dendritic and synaptic conductances within a plausible range constrained by experimental evidence. In contrast, the input-output relationship in response to distal apical stimuli showed dramatic differences from the other dendritic locations as well as among neurons, and was more sensible to the exact channel densities. Action Editor: Alain Destexhe     

Weak Sinusoidal Electric Fields Entrain Spontaneous Ca Transients in the Dendritic Tufts of CA1 Pyramidal Cells in Rat Hippocampal Slice Preparations

Neurons might interact via electric fields and this notion has been referred to as ephaptic interaction. It has been shown that various types of ion channels are distributed along the dendrites and are capable of supporting generation of dendritic spikes. We hypothesized that generation of dendritic spikes play important roles in the ephaptic interactions either by amplifying the impact of electric fields or by providing current source to generate electric fields. To test if dendritic activities can be modulated by electric fields, we developed a method to monitor local Ca-transients in the dendrites of a neuronal population in acute rat hippocampal slices by applying spinning-disk confocal microscopy and multi-cell dye loading technique. In a condition in which the dendrites of CA1 pyramidal neurons show spontaneous Ca-transients due to added 50 μM 4-aminopyridine to the bathing medium and adjusted extracellular potassium concentration, we examined the impact of sinusoidal electric fields on the Ca-transients. We have found that spontaneously occurring fast-Ca-transients in the tufts of the apical dendrites of CA1 pyramidal neurons can be blocked by applying 1 μM tetrodotoxin, and that the timing of the transients become entrained to sub-threshold 1-4 Hz electric fields with an intensity as weak as 0.84 mV/mm applied parallel to the somato-dendritic axis of the neurons. The extent of entrainment increases with intensity below 5 mV/mm, but does not increase further over the range of 5-20 mV/mm. These results suggest that population of pyramidal cells might be able to detect electric fields with biologically relevant intensity by modulating the timing of dendritic spikes.     

The anatomy of the cerebral cortex of the echidna (Tachyglossus aculeatus)

The cerebral cortex of the echidna is notable for its extensive folding and the positioning of major functional areas towards its caudal extremity. The gyrification of the echidna cortex is comparable in magnitude to prosimians and cortical thickness and neuronal density are similar to that seen in rodents and carnivores. On the other hand, many pyramidal neurons in the cerebral cortex of the echidna are atypical with inverted somata and short or branching apical dendrites. All other broad classes of neurons noted in therian cortex are also present in the echidna, suggesting that the major classes of cortical neurons evolved prior to the divergence of proto- and eutherian lineages. Dendritic spine density on dendrites of echidna pyramidal neurons in somatosensory cortex and apical dendrites of motor cortex pyramidal neurons is lower than that found in eutheria. On the other hand, synaptic morphology, density and distribution in somatosensory cortex are similar to that in eutheria. In summary, although the echidna cerebral cortex displays some structural features, which may limit its functional capacities (e.g. lower spine density on pyramidal neurons), in most structural parameters (e.g. gyrification, cortical area and thickness, neuronal density and types, synaptic morphology and density), it is comparable to eutheria.     

Dendritic morphology of hippocampal and amygdalar neurons in adolescent mice is resilient to genetic differences in stress reactivity

Many studies have shown that chronic stress or corticosterone over-exposure in rodents leads to extensive dendritic remodeling, particularly of principal neurons in the CA3 hippocampal area and the basolateral amygdala. We here investigated to what extent genetic predisposition of mice to high versus low stress reactivity, achieved through selective breeding of CD-1 mice, is also associated with structural plasticity in Golgi-stained neurons. Earlier, it was shown that the highly stress reactive (HR) compared to the intermediate (IR) and low (LR) stress reactive mice line presents a phenotype, with respect to neuroendocrine parameters, sleep architecture, emotional behavior and cognition, that recapitulates some of the features observed in patients suffering from major depression. In late adolescent males of the HR, IR, and LR mouse lines, we observed no significant differences in total dendritic length, number of branch points and branch tips, summated tip order, number of primary dendrites or dendritic complexity of either CA3 pyramidal neurons (apical as well as basal dendrites) or principal neurons in the basolateral amygdala. Apical dendrites of CA1 pyramidal neurons were also unaffected by the differences in stress reactivity of the animals; marginally higher length and complexity of the basal dendrites were found in LR compared to IR but not HR mice. In the same CA1 pyramidal neurons, spine density of distal apical tertiary dendrites was significantly higher in LR compared to IR or HR animals. We tentatively conclude that the dendritic complexity of principal hippocampal and amygdala neurons is remarkably stable in the light of a genetic predisposition to high versus low stress reactivity, while spine density seems more plastic. The latter possibly contributes to the behavioral phenotype of LR versus HR animals.     

Physiology of Layer 5 Pyramidal Neurons in Mouse Primary Visual Cortex: Coincidence Detection through Bursting

L5 pyramidal neurons are the only neocortical cell type with dendrites reaching all six layers of cortex, casting them as one of the main integrators in the cortical column. What is the nature and mode of computation performed in mouse primary visual cortex (V1) given the physiology of L5 pyramidal neurons? First, we experimentally establish active properties of the dendrites of L5 pyramidal neurons of mouse V1 using patch-clamp recordings. Using a detailed multi-compartmental model, we show this physiological setup to be well suited for coincidence detection between basal and apical tuft inputs by controlling the frequency of spike output. We further show how direct inhibition of calcium channels in the dendrites modulates such coincidence detection. To establish the singe-cell computation that this biophysics supports, we show that the combination of frequency-modulation of somatic output by tuft input and (simulated) calcium-channel blockage functionally acts as a composite sigmoidal function. Finally, we explore how this computation provides a mechanism whereby dendritic spiking contributes to orientation tuning in pyramidal neurons.     

Cux1 and Cux2 selectively target basal and apical dendritic compartments of layer II‐III cortical neurons

A number of recent reports implicate the differential regulation of apical and basal dendrites in autism disorders and in the higher functions of the human brain. They show that apical and basal dendrites are functionally specialized and that mechanisms regulating their development have important consequences for neuron function. The molecular identity of layer II‐III neurons of the cerebral cortex is determined by the overlapping expression of Cux1 and Cux2. We previously showed that both Cux1 and Cux2 are necessary and nonredundant for normal dendrite development of layer II‐III neurons. Loss of function of either gene reduced dendrite arbors, while overexpression increased dendritic complexity and suggested additive functions. We herein characterize the function of Cux1 and Cux2 in the development of apical and basal dendrites. By in vivo loss and gain of function analysis, we show that while the expression level of either Cux1 or Cux2 influences both apical and basal dendrites, they have distinct effects. Changes in Cux1 result in a marked effect on the development of the basal compartment whereas modulation of Cux2 has a stronger influence on the apical compartment. These distinct effects of Cux genes might account for the functional diversification of layer II‐III neurons into different subpopulations, possibly with distinct connectivity patterns and modes of neuron response. Our data suggest that by their differential effects on basal and apical dendrites, Cux1 and Cux2 can promote the integration of layer II‐III neurons in the intracortical networks in highly specific ways. © 2014 Wiley Periodicals, Inc. Develop Neurobiol 75: 163–172, 2015     

Intrinsic organization of the medial cerebral cortex of the lizard Lacerta pityusensis: A golgi study

The morphology of cells and the organization of axons were studied in Golgi-Colonnier and toluidine blue stained preparations from the medial cerebral cortex of the lizard Lacerta pityusensis. In the medial cortex, six strata were distinguished between the superficial glial membrane and the ependyma. Strata I and II formed the outer plexiform layer, stratum III formed the cellular layer, and strata IV go VI the inner plexiform layer. The outer plexiform layer contained smooth bipolar neurons; their dendrites were oriented anteroposteriorly and their axons were directed towards the posterior zone of the brain. Five neuronal types were observed in the cellular layer. The spinous pyramidal neurons had well-developed apical dendrites and poorly developed basal ones. Their axons entered the inner plexiform layer and gave off collaterals oriented anteroposteriorly. The small, sparsely spinous pyramidal neurons had poorly developed dendrites and their axons entered the inner plexiform layer. The spinous bitufted neurons had well-developed apical and basal dendritic tufts. Their axons gave off collaterals that reached the outer and inner plexiform layers of both the dorsomedial and dorsal cortices. The sparsely spinous horizontal neurons had dendrites restricted to the outer plexiform layer. Their axons entered the inner plexiform layer. The sparsely spinous, multipolar neurons had their soma close to stratum IV and their axons entered the outer plexiform layer. In stratum V of the inner plexiform layer were large, spiny polymorphic neurons; they had dendrites with long spines, and their axons reached the cellular layer. On the basis of these results, we have subdivided the medial cortex into two subregions: the superficial region, which contains the neurons of the cellular layer and their dendritic domains, and the deep region, strata V and VI, which contains the large, spiny polymorphic neurons. The neurons in the medial cortex of these lizards resembles those in the area dentata of mammals. On this basis, the superficial region may be compared to the dentate gyrus and the deep region to the hilar region of the hippocampus of mammals.     

Changes of Dendritic Spine Density and Morphology in the Superficial Layers of the Medial Entorhinal Cortex Induced by Extremely Low-Frequency Magnetic Field Exposure

In the present study, we investigated the effects of chronic exposure (14 and 28 days) to a 0.5 mT 50 Hz extremely low-frequency magnetic field (ELM) on the dendritic spine density and shape in the superficial layers of the medial entorhinal cortex (MEC). We performed Golgi staining to reveal the dendritic spines of the principal neurons in rats. The results showed that ELM exposure induced a decrease in the spine density in the dendrites of stellate neurons and the basal dendrites of pyramidal neurons at both 14 days and 28 days, which was largely due to the loss of the thin and branched spines. The alteration in the density of mushroom and stubby spines post ELM exposure was cell-type specific. For the stellate neurons, ELM exposure slightly increased the density of stubby spines at 28 days, while it did not affect the density of mushroom spines at the same time. In the basal dendrites of pyramidal neurons, we observed a significant decrease in the mushroom spine density only at the later time point post ELM exposure, while the stubby spine density was reduced at 14 days and partially restored at 28 days post ELM exposure. ELM exposure-induced reduction in the spine density in the apical dendrites of pyramidal neurons was only observed at 28 days, reflecting the distinct vulnerability of spines in the apical and basal dendrites. Considering the changes in spine number and shape are involved in synaptic plasticity and the MEC is a part of neural network that is closely related to learning and memory, these findings may be helpful for explaining the ELM exposure-induced impairment in cognitive functions.     

Morphological correlates of pyramidal cell adaptation rate in the electrosensory lateral line lobe of weakly electric fish

1. Extracellular HRP injections into the nucleus praeeminentialis dorsalis (NPd) of Apteronotus leptorhynchus retrogradely labeled a population of electrosensory lateral line lobe (ELL) efferent cells, deep basilar pyramidal cells, that differ morphologically from the previously described basilar and nonbasilar pyramidal cells. These neurons are found deep in the ELL cellular layers; they have small cell bodies and very short sparsely branching apical dendritic trees. The previously described basilar and nonbasilar pyramidal cells are larger, have extensive apical dendrites and are found more superficially. 2. Axon terminals of the deep basilar pyramidal cells were recorded from in the NPd and labeled with lucifer yellow. These NPd afferents have high, regular spontaneous firing rates, and respond tonically to changes in electric organ discharge amplitude. 3. Deep basilar pyramidal cell bodies were recorded from and labeled in the ELL, and these showed the same physiological responses as did the NPd afferent fibers. 4. In addition, basilar pyramidal cells were found which had spontaneous activity patterns and adaptation characteristics intermediate to those typical of the superficial basilar pyramidal cells and the deep basilar pyramidal cells. The size of the pyramidal cells' apical dendritic trees and the placement of their somata within the dorsoventral extent of the ELL cellular layers are highly correlated with the neurons' physiological properties.     

Laminar analysis of the origin of the various components of evoked potentials in slices of rat sensorimotor cortex

In slices of rat sensorimotor cortex, extracellular field potentials evoked by electrical stimulation of the white matter were recorded at various cortical depths. In order to determine the nature of the various components, experiments were performed in 3 situations: in a control perfusion medium, in a solution in which calcium ions have been replaced by magnesium ions to block synaptic transmission, and in cortices in which the pyramidal neurons of layer V had been previously induced to degenerate.In the control situation, the response at or near the surface was a positive-negative wave. From a depth of about 150 μm downwards, the evoked response consisted usually of 6 successive components, 3 positive-going, P11, P3 and P6 and 3 negative-going, N2, N4 and N5. P1 and N4 were apparent in superficial layers only. The amplitude of the remaining waves variable in the cortex but all diminished near the white matter.The early part of the surface positive wave arises from a non-synaptic activation of superficial elements, probably apical dendrites. The late part of the surface positive wave and the negative wave are due to the synaptic activation of neurons located probably in layer III.The large negative wave N2 represents principally the antidromic activation of cell bodies and possibly of proximal dendrites of neurons situated in layers III, IV and V, through the compound action potentials of afferent and efferent fibers may contribute to a reduced part to its generation.The late components N4 to P6 are post-synaptic responses. The negative component N5, the amplitude of which is largest in layers III and IV, represents excitatory responses of neurons located at various depths in the cortex. The nature of the positive component P6 is less clear, although the underlying mechanism might be inhibitory synaptic potentials.     

Ontogenesis of the spine-free initial zone of apical dendrites; studies in cortical pyramidal cells of albino rat]

1. In Golgi-Cox-impregnated coronal sections of albino rat brains at 1, 4, 26, 24, 30, 60 and 90 days it is presented the evolution of the spine-less, bare initial zone ("nude zone", NZ) at the proximal apical main dendrites of the layer V pyramidal neurons in the somatosensory and anterior limbie cortex. The quantitative results are analyzed by statistical methods. 2. The NZ is comprehended as a morphological correlate of the endodendritic neuroplasmic flow (Weiss 1944, Globus, Lux and Schuberl 1968, Kreutzberg 1973). The observed changes of the percental frequency and the average length of NZ increases rapidly. 3. The NZ occurs at first in the (12th) 16 postnatal day, thus in a time, when the organs of hearing and the eyes are differentiated completely. Between 16th and 24th day the percental frequency as well as the longitude of NZ increases. During this time the rats will be independent of the mother animals. With the full differentiation of the urogenital tract and especially with the sexual maturity the percentage frequency of NZ increases only at pyramidal cells in the anterior limbie cortex between 24th and 60th day. During 3rd month the NZ is occuring percental more frequently in the anterior limbic cortex than in the somatosensory cortex. At this time the average length of NZ is shorter in the limbic cortex. 4. As to the enriched, vivid movement of the animals and the playing impulse of the young rats the average length of NZ will be extended at pyramidal neurons in the somatosensory cortex during 2nd month, as well as the pattern of spine distribution will be changed along apical dendrites (Schlerhorn, unpublished). During the following (3rd) month the NZ will be shorteded in the somatosensory cortex, obviously caused by new formation of spines at the proximal main dendrites. 5. These newly formed spines in the initial zone of apical dendrites may be inhibitory spines. The inhibitory spines are stained only when using the mercury chromate impregnation according to Golgi-Cox, but not when using the silver chromate methods according to Golgi-Kopsch or Golgi-Bubenaite. The different tingibility of these spines by different Golgi techniques is discussed by Doedens, Nagel and Schierhorn (1974). The pyramidal neurons in the somatosensory cortex possess a longer average length of NZ (Lnz = 7,3[mum]) than the pyramidal cells in the anterior limbic cortex (Lnz = 6.2[mum]). As to NZ the differences between silver and mercury chromate stained pyramidal neurons are greater in the somatosensory cortex than in limbic cortex (see Tab. 7). Therefore we assume that there are in the initial zone of somatosensory pyramidal neurons more inhibitory spines than at the pyramidal neurons in the anterior limbic cortex. 6. The regional differences in the percentual frequency and in the average length of NZ between somatosensory and limbic cortex are new identifying marks of architectonic differentiation of the pyramidal neurons in cortical regions of phylogenetically different ages.     

Cell type-specific dendritic polarity in the absence of spatially organized external cues

Pyramidal neurons of the hippocampus and cortex have polarized dendritic arbors, but little is known about the cellular mechanisms distinguishing apical and basal dendrites. We used morphometric analysis and time lapse imaging of cultured hippocampal neurons to show that glutamatergic neurons develop progressive dendritic asymmetry in the absence of polarized extrinsic cues. Thus, pyramidal neurons have a cellular program for polarized dendrite growth independent of tissue microenvironment.     

Local Diameter Fully Constrains Dendritic Size in Basal but not Apical Trees of CA1 Pyramidal Neurons

Computational modeling of dendritic morphology is a powerful tool for quantitatively describing complex geometrical relationships, uncovering principles of dendritic development, and synthesizing virtual neurons to systematically investigate cellular biophysics and network dynamics. A feature common to many morphological models is a dependence of the branching probability on local diameter. Previous models of this type have been able to recreate a wide variety of dendritic morphologies. However, these diameter-dependent models have so far failed to properly constrain branching when applied to hippocampal CA1 pyramidal cells, leading to explosive growth. Here we present a simple modification of this basic approach, in which all parameter sampling, not just bifurcation probability, depends on branch diameter. This added constraint prevents explosive growth in both apical and basal trees of simulated CA1 neurons, yielding arborizations with average numbers and patterns of bifurcations extremely close to those observed in real cells. However, simulated apical trees are much more varied in size than the corresponding real dendrites. We show that, in this model, the excessive variability of simulated trees is a direct consequence of the natural variability of diameter changes at and between bifurcations observed in apical, but not basal, dendrites. Conversely, some aspects of branch distribution were better matched by virtual apical trees than by virtual basal trees. Dendritic morphometrics related to spatial position, such as path distance from the soma or branch order, may be necessary to fully constrain CA1 apical tree size and basal branching pattern.     

CRMP4 suppresses apical dendrite bifurcation of CA1 pyramidal neurons in the mouse hippocampus

Collapsin response mediator proteins (CRMPs) are a family of cytosolic phosphoproteins that consist of 5 members (CRMP 1–5). CRMP2 and CRMP4 regulate neurite outgrowth by binding to tubulin heterodimers, resulting in the assembly of microtubules. CRMP2 also mediates the growth cone collapse response to the repulsive guidance molecule semaphorin‐3A (Sema3A). However, the role of CRMP4 in Sema3A signaling and its function in the developing mouse brain remain unclear. We generated CRMP4?/? mice in order to study the in vivo function of CRMP4 and identified a phenotype of proximal bifurcation of apical dendrites in the CA1 pyramidal neurons of CRMP4?/? mice. We also observed increased dendritic branching in cultured CRMP4?/? hippocampal neurons as well as in cultured cortical neurons treated with CRMP4 shRNA. Sema3A induces extension and branching of the dendrites of hippocampal neurons; however, these inductions were compromised in the CRMP4?/? hippocampal neurons. These results suggest that CRMP4 suppresses apical dendrite bifurcation of CA1 pyramidal neurons in the mouse hippocampus and that this is partly dependent on Sema3A signaling. © 2012 Wiley Periodicals, Inc. Develop Neurobiol, 2012