Morphology Of Pyramidal Neurons Research Articles

Anterior piriform cortex dysfunction underlies autism spectrum disorders-related olfactory deficits in Fmr1 conditional deletion mice.

Previous studies indicated that ASD-related olfactory dysfunctions are rooted in the piriform cortex. However, the direct evidence supporting a causal link between the dysfunction of the piriform cortex and olfactory disorders in ASD is limited. In the present study, we explored the role of anterior piriform cortex (aPC) in ASD-related olfactory disorders by specifically ablating Fmr1, a leading known monogenic cause for ASD, in the pyramidal neurons. Our data demonstrated that the targeted deletion of Fmr1 in aPC pyramidal neurons was sufficient to induce deficits in olfactory detection. In vivo and in vitro electrophysiological recordings showed that the deletion of Fmr1 increased the activity of pyramidal neurons, exhibiting an enhanced excitatory response and a reduced inhibitory response upon odor stimulation. Furthermore, specific deletion of Fmr1 enhanced the power of beta oscillations during odor stimuli, meanwhile, disturbed excitatory and inhibitory synaptic transmission. The abnormal morphology of pyramidal neurons induced by the deletion of Fmr1 may be responsible for the impaired aPC neuronal function. These findings suggest that dysfunction of the aPC may play a role in olfactory impairments observed in ASD models related to Fmr1 deficiency.

Postnatal Neuronal Nogo-A Knockdown Decreased the Message of Glutamatergic Synaptic Proteins.

It is well known that oligodendrocyte-associated Nogo-A protein is an important regulator of axonal outgrowth and an important inhibitor of functional recovery and anatomical plasticity after central nervous system (CNS) injury. Abundant studies of oligodendrocyte-associated Nogo-A function in the uninjured rodent have suggested a role in neuronal development and synaptic function. On the other hand, the roles of neuron-associated (i.e., neuronal) Nogo-A have not been fully investigated. We have previously shown that neuronal Nogo-A influence dendritic spine density and morphology in pyramidal neurons of the intact neocortex. To further examine the role of neuronal Nogo-A in this synaptic population, we designed an RNAi directed against Nogo-A, delivered to the developing rat sensorimotor cortex using a neurotropic viral vector adeno-associated virus (AAV) 2/8. We examined the transduced neocortex for molecules important for synaptic plasticity, including N-Methyl-D-Aspartate (NMDA) receptor subunits GRIN2A; glutamate receptor subunit epsilon-1 (NR2A), and GRIN2B; glutamate receptor subunit epsilon-2 (NR2B), as well as postsynaptic density-95 (PSD-95). Furthermore, we also determined the density of excitatory synapses by examining the presynaptic protein vesicular glutamate transporter 1 (vGLut1) as a marker for potential excitatory synapses. Our results showed that neuronal Nogo-A knockdown in postnatal pyramidal neurons of the sensorimotor cortex led to a significant decrease in NMDA receptor subunits NR2A and NR2B messenger RNA when examined as adults. However, there was no difference in PSD-95 expression in comparison to controls. In addition, the decrease in the number of vGlut1(+) puncta on branches of apical dendrites of pyramidal neurons indicated the loss of synapses that have a strong influence on direct current entering the dendrite. Taken together, these results indicate that neuronal Nogo-A may regulate synaptic plasticity by modulating the components of excitatory synapses. This finding represents a novel role in excitatory synaptic formation for neuronal Nogo-A in developing neurons of the uninjured CNS.

Corilagin improves cognitive impairment in APP/PS1 mice by reducing Aβ generation and enhancing synaptic plasticity

Alzheimer's disease (AD) is closely associated with the neurotoxic effects of amyloid-β (Aβ), leading to synaptic damage, neuronal loss and cognitive dysfunction. Previous in vitro studies have demonstrated the potential of corilagin to counteract Aβ-induced oxidative stress, inflammatory injury, and β-site amyloid precursor protein cleaving enzyme-1 (BACE1) activity in Aβ production. However, the in vivo protective effects of corilagin on Alzheimer's disease remain unexplored. The purpose of this study was to investigate the protective effects of corilagin on APP/PS1 mice and the underlying mechanisms. The cognitive function of the mice was assessed by step-through passive avoidance and Morris water maze tests. Nissl staining was used to evaluate neuronal damage in the hippocampus. ELISA and Western blotting analyses were used to determine the associated protein expression. Transmission electron microscopy was utilized to observe the synaptic ultrastructure of hippocampal neurons. Golgi staining was applied to assess dendritic morphology and dendritic spine density in hippocampal pyramidal neurons. Immunohistochemistry and Western blotting were performed to examine the expression of synaptic-associated proteins. The results showed that corilagin improves learning and memory in APP/PS1 mice, reduces hippocampal neuron damage, inhibits BACE1 and reduces Aβ generation. It also improves synaptic plasticity and the expression of synaptic-associated proteins. Corilagin effectively reduces Aβ generation by inhibiting BACE1, ultimately reducing neuronal loss and enhancing synaptic plasticity to improve synaptic transmission. This study sheds light on the potential therapeutic role of corilagin in Alzheimer's disease.

Recovery of Learning and Memory Deficits Despite Persistent Pyknosis of the Hippocampal Pyramidal Neurons of Adult Hydrocephalic Mice.

The hippocampal alterations resulting from hydrocephalus are associated with various cognitive dysfunctions. Reduced learning and memory are early functional deficits that recover with time in experimental hydrocephalus. This study investigated the recovery processes of learning and memory loss in relation to the morphology of hippocampal pyramidal neurons and the degree of expansion of the ventricles. Hydrocephalus was induced in adult mice by intracisternal injection of sterile kaolin while controls received sham operation. Neurobehavioral tests for memory and learning were conducted, after which the animals were sacrificed in batches: 7 (acute) and 28 (subacute) days postinduction. After sacrifice, mice were categorized into mild and moderate hydrocephalus, and their fixed brain samples were processed for hematoxylin, eosin, and Nissl stains. In moderate acute hydrocephalus, the indices of learning and memory were reduced escape latency (67.20 ± 12.83 s), number of platform crossing (4.000 ± 1.658), duration in platform quadrant (4.000 ± 1.658), and percent of total investigation (44.857% ± 3.981%) but not in the subacute stage. Pyknotic indices (PI) were significantly higher in the cornu ammonis (CA)1 and 3 regions in all hydrocephalic groups than in controls. However, within groups, PI was significantly higher only in the CA1 of moderate acute (28.149% ± 1.875%) compared to moderate subacute hydrocephalic group (12.903% ± 3.23%). Hydrocephalus caused cellular injury to the hippocampus associated with spatial learning and memory deficits. However, these functional deficits were partially reversed in moderate subacute hydrocephalus despite the persistence of the structural alterations in the CA1 and CA3 subregions.

Kamishoyosan Normalizes Dendritic Spine Morphology in the Medial Prefrontal Cortex by Regulating microRNA-18 and Glucocorticoid Receptor Expressions in Postmenopausal Chronic Stress-Exposed Mice.

Kamishoyosan (KSS), a traditional Japanese Kampo medicine, is widely used to treat neuropsychiatric symptoms in perimenopausal and postmenopausal women. We aimed to elucidate the functional mechanisms underlying KSS-mediated reduction of stress response behaviors and neuropsychological symptoms in perimenopausal and postmenopausal women. Female mice were bilaterally ovariectomized (OVX) at the age of 12 weeks and exposed to chronic water immersion and restraint stress for three weeks. Among them, mice in the OVX+stress+KSS group were fed chow containing KSS from one week before exposure to chronic stress until the end of the experiment. Firstly, we performed a marble burying test and measured serum corticosterone levels to assess irritability and stress conditions. Next, we examined whether KSS affects microRNA-18 (miR-18) and glucocorticoid receptor (GR) protein expression, as well as the basal dendritic spine morphology of pyramidal neurons in the medial prefrontal cortex (mPFC) of postmenopausal chronic stress-exposed mice. Analyzed data were expressed as mean ± standard deviation. Tukey's post hoc test, followed by analysis of variance (ANOVA), was used for among-group comparisons. KSS administration normalized chronic stress-induced unstable emotion-like behavior and upregulated plasma corticosterone levels. Furthermore, KSS ameliorated GR protein expression by downregulating miR-18 expression in the mPFC and recovered the immature morphological changes in spine formation of pyramidal neurons in the mPFC of OVX mice following chronic stress exposure. KSS administration in postmenopausal chronic stress-exposed mice exerted anti-stress effects and improved the basal dendritic spine morphology of pyramidal neurons by regulating miR-18 and glucocorticoid receptor expression in the mPFC.

Enigma of Pyramidal Neurons: Chirality-Centric View on Biological Evolution. Congruence to Molecular, Cellular, Physiological, Cognitive, and Psychological Functions

The mechanism of brain information processing unfolds within spatial and temporal domains inherently linked to the concept of space–time symmetry. Biological evolution, beginning with the prevalent molecular chirality, results in the handedness of human cognitive and psychological functions (the phenomena known as biochirality). The key element in the chain of chirality transfer from the downstream to upstream processes is the pyramidal neuron (PyrN) morphology–function paradigm (archetype). The most apparent landmark of PyrNs is the geometry of the cell soma. However, “why/how PyrN’s soma gains the shape of quasi-tetrahedral symmetry” has never been explicitly articulated. Resolving the above inquiry is only possible based on the broad-view assumption that encoding 3D space requires specific 3D geometry of the neuronal detector and corresponding network. Accordingly, our hypothesis states that if the primary function of PyrNs, at the organism level, is sensory space symmetry perception, then the pyramidal shape of soma is the best evolutionary-selected geometry to support sensory-motor coupling. The biological system’s non-equilibrium (NE) state is fundamentally linked to an asymmetric, non-racemic, steady state of molecular constituents. The chiral theory of pyramidal soma shape conceptually agrees that living systems have evolved as non-equilibrium systems that exchange energy with the environment. The molecular mechanism involved in developing PyrN’s soma is studied in detail. However, the crucial missing element—the reference to the fundamental link between molecular chirality and the function of spatial navigation—is the main obstacle to resolving the question in demand: why did PyrNs’ soma gain the shape of quasi-tetrahedral symmetry?

The mTOR pathway genes MTOR, Rheb, Depdc5, Pten, and Tsc1 have convergent and divergent impacts on cortical neuron development and function

Brain somatic mutations in various components of the mTOR complex 1 (mTORC1) pathway have emerged as major causes of focal malformations of cortical development and intractable epilepsy. While these distinct gene mutations converge on excessive mTORC1 signaling and lead to common clinical manifestations, it remains unclear whether they cause similar cellular and synaptic disruptions underlying cortical network hyperexcitability. Here, we show that in utero activation of the mTORC1 activator genes, Rheb or MTOR, or biallelic inactivation of the mTORC1 repressor genes, Depdc5, Tsc1, or Pten in the mouse medial prefrontal cortex leads to shared alterations in pyramidal neuron morphology, positioning, and membrane excitability but different changes in excitatory synaptic transmission. Our findings suggest that, despite converging on mTORC1 signaling, mutations in different mTORC1 pathway genes differentially impact cortical excitatory synaptic activity, which may confer gene-specific mechanisms of hyperexcitability and responses to therapeutic intervention.

The mTOR pathway genes MTOR, Rheb, Depdc5, Pten, and Tsc1 have convergent and divergent impacts on cortical neuron development and function.

Brain somatic mutations in various components of the mTOR complex 1 (mTORC1) pathway have emerged as major causes of focal malformations of cortical development and intractable epilepsy. While these distinct gene mutations converge on excessive mTORC1 signaling and lead to common clinical manifestations, it remains unclear whether they cause similar cellular and synaptic disruptions underlying cortical network hyperexcitability. Here, we show that in utero activation of the mTORC1 activator genes, Rheb or MTOR, or biallelic inactivation of the mTORC1 repressor genes, Depdc5, Tsc1, or Pten in the mouse medial prefrontal cortex leads to shared alterations in pyramidal neuron morphology, positioning, and membrane excitability but different changes in excitatory synaptic transmission. Our findings suggest that, despite converging on mTORC1 signaling, mutations in different mTORC1 pathway genes differentially impact cortical excitatory synaptic activity, which may confer gene-specific mechanisms of hyperexcitability and responses to therapeutic intervention.

Sex-specific dendritic morphology of hippocampal pyramidal neurons in the adolescent and young adult rats.

CA1 and CA3 pyramidal neurons are the major sources of hippocampal efferents. The structural features of these neurons are presumed to be involved in various normal/abnormal cognitive and emotional outcomes by influencing the pattern of synaptic inputs and neuronal signal processing. Although many studies have described hippocampal structure differences between males and females, these reports mainly focused on gross anatomical features in adult or aged models, and such distinctions on neuronal morphology and dendritic spine density during adolescence, a period of high vulnerability to neurodevelopmental disorders, have received much less attention. In this work, we analyzed dendritic architecture and density of spines in CA1 and CA3 neurons of male and female rats in early adolescence (postnatal day, PND 40) and compared them with those in late adolescence/young adulthood (PND 60). On PND 40, CA1 neurons of male rats showed more Sholl intersections and spine density in apical and basal dendrites compared to those in females. The Sholl intersections in basal dendrites of CA3 neurons were also more in males, whereas the number of apical dendrite intersections was not significantly different between sexes. In male rats, there was a notable decrease in the number of branch and terminal points in the basal dendrite of CA1 neurons of young adults when compared to their sex-matched adolescent rats. On the other hand, CA1 neurons in young adult females also showed more Sholl intersections in apical and basal dendrites compared to adolescent females. Meanwhile, the total cable length, the number of branches, and terminal points of apical dendrites in CA3 neurons also exhibited a significant reduction in young adult male rats compared to their sex-matched adolescents. In young adult rats, both apical and basal dendrites of CA3 neurons in males showed fewer intersections with Sholl circles, but there were no significant differences in dendritic spine density or count estimation between males and females. On the other hand, young adult female rats had more Sholl intersections and dendritic spine count on the basal dendrites of CA3 neurons compared to adolescent females. Although no significant sex- and age-dependent difference in neuronal density was detected in CA1 and CA3 subareas, CA3 pyramidal neurons of both male and female rats showed reduced soma area compared to adolescent rats. Our findings show that the sex differences in the dendritic structure of CA1 and CA3 neurons vary by age and also by the compartments of dendritic arbors. Such variations in the morphology of hippocampal pyramidal neurons may take part as a basis for normal cognitive and affective differences between the sexes, as well as distinct sensitivity to interfering factors and the prevalence of neuropsychological diseases.

G-CSF improved the memory and dendritic morphology impairments in the hippocampal CA1 pyramidal neurons after brain ischemia in the male rats.

Stroke remains the leading cause of death and disability in the world. A new potential treatment for stroke is the granulocyte colony-stimulating factor (G-CSF), which exerts neuroprotective effects through multiple mechanisms. Memory impairment is the most common cognitive problem after a stroke. The suggested treatment for memory impairments is cognitive rehabilitation, which is often ineffective. The hippocampus plays an important role in memory formation. This project aimed to study the effect of G-CSF on memory and dendritic morphology of hippocampal CA1 pyramidal neurons after middle cerebral artery occlusion (MCAO)in rats. Male Sprague-Dawley rats were divided into three groups: the sham, control (MCAO + Vehicle), and treatment (MCAO + G-CSF) groups. G-CSF (50µg/kg S.C) was administered at 6, 24, and 48h after brain ischemia induction. The passive avoidance task to evaluate learning and memory was performed on days 6 and 7 post-ischemia. Seven days after MCAO, the brain was removed and the hippocampal slices were stained with Golgi. After that, the neurons were analyzed for dendritic morphology and maturity. The data showed that stroke was associated with a significant impairment in the acquisition and retention of passive avoidance tasks, while the G-CSF improved learning and memory loss. The dendritic length, arborization, spine density, and mature spines of the hippocampus CA1 neurons were significantly reduced in the control group, and treatment with G-CSF significantly increased these parameters. G-CSF, even with three doses, improved learning and memory deficits, and dendritic morphological changes in the CA1 hippocampal neurons resulted from brain ischemia.

Inferring Pyramidal Neuron Morphology using EAP Data.

We report a computational algorithm that uses an inverse modeling scheme to infer neuron position and morphology of cortical pyramidal neurons using spatio-temporal extracellular action potential recordings.. We first develop a generic pyramidal neuron model with stylized morphology and active channels that could mimic the realistic electrophysiological dynamics of pyramidal cells from different cortical layers. The generic stylized single neuron model has adjustable parameters for soma location, and morphology and orientation of the dendrites. The ranges for the parameters were selected to include morphology of the pyramidal neuron types in the rodent primary motor cortex. We then developed a machine learning approach that uses the local field potential simulated from the stylized model for training a convolutional neural network that predicts the parameters of the stylized neuron model. Preliminary results suggest that the proposed methodology can reliably infer the key position and morphology parameters using the simulated spatio-temporal profile of EAP waveforms. We also provide partial support to validate the inference algorithm using in vivo data. Finally, we highlight the issues involved and ongoing work to develop a pipeline to automate the scheme.

Neonatal sevoflurane exposure induces long-term changes in dendritic morphology in juvenile rats and mice.

General anesthetics are potent neurotoxins when given during early development, causing apoptotic deletion of substantial number of neurons and persistent neurocognitive and behavioral deficits in animals and humans. The period of intense synaptogenesis coincides with the peak of susceptibility to deleterious effects of anesthetics, a phenomenon particularly pronounced in vulnerable brain regions such as subiculum. With steadily accumulating evidence confirming that clinical doses and durations of anesthetics may permanently alter the physiological trajectory of brain development, we set out to investigate the long-term consequences on dendritic morphology of subicular pyramidal neurons and expression on genes regulating the complex neural processes such as neuronal connectivity, learning, and memory. Using a well-established model of anesthetic neurotoxicity in rats and mice neonatally exposed to sevoflurane, a volatile general anesthetic commonly used in pediatric anesthesia, we report that a single 6 h of continuous anesthesia administered at postnatal day (PND) 7 resulted in lasting dysregulation in subicular mRNA levels of cAMP responsive element modulator (Crem), cAMP responsive element-binding protein 1 (Creb1), and Protein phosphatase 3 catalytic subunit alpha, a subunit of calcineurin (Ppp3ca) (calcineurin) when examined during juvenile period at PND28. Given the critical role of these genes in synaptic development and neuronal plasticity, we deployed a set of histological measurements to investigate the implications of anesthesia-induced dysregulation of gene expression on morphology and complexity of surviving subicular pyramidal neurons. Our results indicate that neonatal exposure to sevoflurane induced lasting rearrangement of subicular dendrites, resulting in higher orders of complexity and increased branching with no significant effects on the soma of pyramidal neurons. Correspondingly, changes in dendritic complexity were paralleled by the increased spine density on apical dendrites, further highlighting the scope of anesthesia-induced dysregulation of synaptic development. We conclude that neonatal sevoflurane induced persistent genetic and morphological dysregulation in juvenile rodents, which could indicate heightened susceptibility toward cognitive and behavioral disorders we are beginning to recognize as sequelae of early-in-life anesthesia.

Integrin β3 regulates apical dendritic morphology of pyramidal neurons throughout hippocampal CA3.

In excitatory hippocampal pyramidal neurons, integrin β3 is critical for synaptic maturation and plasticity in vitro. Itgb3 is a potential autism susceptibility gene that regulates dendritic morphology in the cerebral cortex in a cell-specific manner. However, it is unknown what role Itgb3 could have in regulating hippocampal pyramidal dendritic morphology in vivo, a key feature that is aberrant in many forms of autism and intellectual disability. We found that Itgb3 mRNA is expressed in the stratum pyramidale of CA3. We examined the apical dendritic morphology of CA3 hippocampal pyramidal neurons in conditional Itgb3 knockouts and controls, utilizing the Thy1-GFP-M line. We fully reconstructed the apical dendrite of each neuron and determined each neuron's precise location along the dorsoventral, proximodistal, and radial axes of the stratum pyramidale. We found a very strong effect for Itgb3 expression on CA3 apical dendritic morphology: neurons from conditional Itgb3 knockouts had longer and thinner apical dendrites than controls, particularly in higher branch orders. We also assessed potential relationships between pairs of topographic or morphological variables, finding that most variable pairs were free from any linear relationships to each other. We also found that some neurons from controls, but not conditional Itgb3 knockouts, had a graded pattern of overall diameter along the dorsoventral and proximodistal axes of the stratum pyramidale of CA3. Taken together, Itgb3 is essential for constructing normal dendritic morphology in pyramidal neurons throughout CA3.

Sex differences in hippocampal structural plasticity and glycosaminoglycan disaccharide levels after neonatal handling.

In this study we investigated the effects of a neonatal handling protocol that mimics the handling of sham control pups in protocols of neonatal exposure to brain insults on dendritic arborization and glycosaminoglycan (GAG) levels in the developing brain. GAGs are long, unbranched polysaccharides, consisting of repeating disaccharide units that can be modified by sulfation at specific sites and are involved in modulating neuronal plasticity during brain development. In this study, male and female Sprague-Dawley rats underwent neonatal handling daily between post-natal day (PD)4 and PD9, with brains analyzed on PD9. Neuronal morphology and morphometric analysis of the apical and basal dendritic trees of CA1 hippocampal pyramidal neurons were carried out by Golgi-Cox staining followed by neuron tracing and analysis with the software Neurolucida. Chondroitin sulfate (CS)-, Hyaluronic Acid (HA)-, and Heparan Sulfate (HS)-GAG disaccharide levels were quantified in the hippocampus by Liquid Chromatography/Mass Spectrometry analyses. We found sex by neonatal handling interactions on several parameters of CA1 pyramidal neuron morphology and in the levels of HS-GAGs, with females, but not males, showing an increase in both dendritic arborization and HS-GAG levels. We also observed increased expression of glucocorticoid receptor gene Nr3c1 in the hippocampus of both males and females following neonatal handling suggesting that both sexes experienced a similar stress during the handling procedure. This is the first study to show sex differences in two parameters of brain plasticity, CA1 neuron morphology and HS-GAG levels, following handling stress in neonatal rats.

Simultaneous 3D cellular positioning and apical dendritic morphology of transgenic fluorescent mouse CA3 hippocampal pyramidal neurons

BackgroundPyramidal neurons throughout hippocampal CA3 are diverse in their dendritic morphology, and CA3 is not homogenous in its structure or function. Nonetheless, few structural studies have captured the precise 3D somatic position and the 3D dendritic morphology of CA3 pyramidal neurons simultaneously. New methodHere, we present a simple approach to reconstruct the apical dendritic morphology of CA3 pyramidal neurons using the transgenic fluorescent Thy1-GFP-M line. The approach simultaneously tracks the dorsoventral, tangential, and radial positions of reconstructed neurons within the hippocampus. It is especially designed for use with transgenic fluorescent mouse lines, which are commonly used in genetic studies of neuronal morphology and development. ResultsWe demonstrate how topographic and morphological data are captured from transgenic fluorescent mouse CA3 pyramidal neurons. Comparison with existing methodsThere is no need to select and label CA3 pyramidal neurons with the transgenic fluorescent Thy1-GFP-M line. By taking transverse (not coronal) serial sections, we preserve fine dorsoventral, tangential, and radial somatic positioning of 3D-reconstructed neurons. Because CA2 is well defined by PCP4 immunohistochemistry, we use that technique here to to increase precision in defining tangential position along CA3. ConclusionsWe developed a method for simultaneously collecting precise somatic positioning as well as 3D morphological data among transgenic fluorescent mouse hippocampal pyramidal neurons. This fluorescent method should be compatible with many other transgenic fluorescent reporter lines and immunohistochemical methods, facilitating the capture of topographic and morphological data from a wide variety of genetic experiments in mouse hippocampus.

Vanadium improves memory and spatial learning and protects the pyramidal cells of the hippocampus in juvenile hydrocephalic mice.

Hydrocephalus is a neurological condition known to cause learning and memory disabilities due to its damaging effect on the hippocampal neurons, especially pyramidal neurons. Vanadium at low doses has been observed to improve learning and memory abilities in neurological disorders but it is uncertain whether such protection will be provided in hydrocephalus. We investigated the morphology of hippocampal pyramidal neurons and neurobehavior in vanadium-treated and control juvenile hydrocephalic mice. Hydrocephalus was induced by intra-cisternal injection of sterile-kaolin into juvenile mice which were then allocated into 4 groups of 10 pups each, with one group serving as an untreated hydrocephalic control while others were treated with 0.15, 0.3 and 3 mg/kg i.p of vanadium compound respectively, starting 7 days post-induction for 28 days. Non-hydrocephalic sham controls (n = 10) were sham operated without any treatment. Mice were weighed before dosing and sacrifice. Y-maze, Morris Water Maze and Novel Object Recognition tests were carried out before the sacrifice, the brains harvested, and processed for Cresyl Violet and immunohistochemistry for neurons (NeuN) and astrocytes (GFAP). The pyramidal neurons of the CA1 and CA3 regions of the hippocampus were assessed qualitatively and quantitatively. Data were analyzed using GraphPad prism 8. Escape latencies of vanadium-treated groups were significantly shorter (45.30 ± 26.30 s, 46.50 ± 26.35 s, 42.99 ± 18.44 s) than untreated group (62.06 ± 24.02 s) suggesting improvements in learning abilities. Time spent in the correct quadrant was significantly shorter in the untreated group (21.19 ± 4.15 s) compared to control (34.15 ± 9.44 s) and 3 mg/kg vanadium-treated group (34.35 ± 9.74 s). Recognition index and mean % alternation were lowest in untreated group (p = 0.0431, p=0.0158) suggesting memory impairments, with insignificant improvements in vanadium-treated groups. NeuN immuno-stained CA1 revealed loss of apical dendrites of the pyramidal cells in untreated hydrocephalus group relative to control and a gradual reversal attempt in the vanadium-treated groups. Astrocytic activation (GFAP stain) in the untreated hydrocephalus group were attenuated in the vanadium-treated groups under the GFAP stain. Pyknotic index in CA1 pyramidal layer of untreated (18.82 ± 2.59) and 0.15mg/kg vanadium-treated groups (18.14 ± 5.92) were significantly higher than control (11.11 ± 0.93; p = 0.0205, p = 0.0373) while there was no significant difference in CA3 pyknotic index across all groups. Our results suggest that vanadium has a dose-dependent protective effect on the pyramidal cells of the hippocampus and on memory and spatial learning functions in juvenile hydrocephalic mice.

Facial nerve axotomy induces morphological changes in hippocampal pyramidal neurons.

Facial nerve injury in rats have been widely used to study functional and structural changes that occur in the injured motoneurons and other central nervous system structures related with sensorimotor processing. A decrease in long-term potentiation of hippocampal CA3-to-CA1 commissural synapse has recently been reported related to this peripheral injury. Additionally, it has been found increased corticosterone plasmatic levels, impairment in spatial memory consolidation, and hippocampal microglial activation in animals with facial nerve axotomy. In this work, we analyzed the neuronal morphology of hippocampal CA1 and CA3 pyramidal neurons in animals with either reversible or irreversible facial nerve injury. For this purpose, brain tissues of injured animals sacrificed at different postlesion times, were stained with the Golgi-Cox method and compared with control brains. It was found that both reversible and irreversible facial nerve injury-induced significant decreases in dendritic tree complexity, dendritic length, branch points, and spine density of hippocampal neurons. However, such changes' timing varied according to hippocampal area (CA1 vs. CA3), dendritic area (apical vs. basal), and lesion type (reversible vs. irreversible). In general, the observed changes were transient when animals had the possibility of motor recovery (reversible injury), but perdurable if the recovery from the lesion was impeded (irreversible injury). CA1 apical and CA3 basal dendritic tree morphology were more sensible to irreversible injury. It is concluded that facial nerve injury induced significant changes in hippocampal CA1 and CA3 pyramidal neurons morphology, which could be related to LTP impairments and microglial activation in the hippocampal formation, previously described.

Postnatal development of electrophysiological and morphological properties in layer 2/3 and layer 5 pyramidal neurons in the mouse primary visual cortex.

Eye-opening is a critical point for laminar maturation of pyramidal neurons (PNs) in primary visual cortex. Knowing both the intrinsic properties and morphology of PNs from the visual cortex during development is crucial to contextualize the integration of visual inputs at different age stages. Few studies have reported changes in intrinsic excitability in these neurons but were restricted to only one layer or one stage of cortical development. Here, we used in vitro whole-cell patch-clamp to investigate the developmental impact on electrophysiological properties of layer 2/3 and layer 5 PNs in mouse visual cortex. Additionally, we evaluated the morphological changes before and after eye-opening and compared these in adult mice. Overall, we found a decrease in intrinsic excitability in both layers after eye-opening which remained stable between juvenile and adult mice. The basal dendritic length increased in layer 5 neurons, whereas spine density increased in layer 2/3 neurons after eye-opening. These data show increased number of synapses after onset of sensory input paralleled with a reduced excitability, presumably as homeostatic mechanism. Altogether, we provide a database of the properties of PNs in mouse visual cortex by considering the layer- and time-specific changes of these neurons during sensory development.

Obese male Zucker rats exhibit dendritic remodeling in neurons of the hippocampal trisynaptic circuit as well as spatial memory deficits.

Obesity is characterized by excessive fat accumulation. The Zucker rat displays genetic obesity due to a mutation in the leptin receptor gene; this model is of great interest because of its similarity to human obesity. Brain regions may be affected by obesity, but detailed information is lacking. In the present study, we analyzed the morphology of neurons in the hippocampal trisynaptic circuit as well as the spatial memory of obese Zucker rats. We performed two experiments. Each experiment contained two experimental groups: the control group (male Long Evans rats) and the study group (obese male Zucker rats). We monitored the body weights of all rats over 4 weeks. In the first experiment, we analyzed the morphology of hippocampal neurons. Under anesthesia, we measured the abdominal and hip circumferences and collected at least 1ml of blood to assess serum glucose (GLU), triglyceride (TGC), and cholesterol (COL) concentrations. We perfused the brains of these rats with 0.9% saline solution, incubated the brains in Golgi-Cox solution, and subsequently evaluated the morphology of pyramidal neurons in the hippocampus (the CA1-CA3 regions) and the entorhinal cortex as well as the morphology of granule neurons in the dentate gyrus. In the second experiment, we assessed the spatial memory of animals with the Morris water maze. The Zucker rats had an obese phenotype, as indicated by their elevated body weight and increased abdominal and hip circumferences as well as elevated GLU, COL, and TGC concentrations. Analysis of neurons from the specified regions in obese male Zucker rats indicated reduced dendritic arborization and reduced dendritic spine density. In terms of spatial learning and memory, the obese Zucker rats exhibited intact spatial learning (i.e., of platform location) but deficits in spatial memory. These data provide evidence that obesity alters the morphology and function of hippocampal neurons.

Cranial irradiation induces cognitive decline associated with altered dendritic spine morphology in the young rat hippocampus.

Therapeutic irradiation is commonly used to treat brain cancers but can induce cognitive dysfunction, especially in children. The mechanism is unknown but likely involves alterations in dendritic spine number and structure. To explore the impact of radiation exposure on the alteration of dendritic spine morphology in the hippocampus of young brains, 21-day-old Sprague-Dawley rats received cranial irradiation (10Gy), and changes in spine density and morphology in dentate gyrus (DG) granules and CA1 pyramidal neurons were detected 1 and 3months later by using Golgi staining. Moreover, we analyzed synapse-associated proteins within dendritic spines after irradiation. Our data showed that cognitive deficits were detected in young rats at both time points postirradiation, accompanied by morphological changes in dendritic spines. Our results revealed significant reductions in spine density in the DG at both 1month (40.58%) and 3months (28.92%) postirradiation. However, there was a decrease in spine density only at 1month (33.29%) postirradiation in the basal dendrites of CA1 neurons and no significant changes in the apical dendrites of CA1 neurons at either time point. Notably, among our findings were the significant dynamic changes in spine morphology that persisted 3months following cranial irradiation. Meanwhile, we found that depletion of the synapse-associated proteins PSD95 and Drebrin coincided with alterations in dendritic spines. These data suggest that the decreased levels of PSD95 and Drebrin after ionizing radiation may cause changes in synaptic plasticity by affecting the morphological structure of dendritic spines, blocking the functional connectivity pathways of the brain and leading to cognitive impairment. Although the mechanism involved is unclear, understanding how ionizing radiation affects young brain hippocampal tissue may be useful to gain new mechanistic insights into radiation-induced cognitive dysfunction.