Changes In Dendritic Spine Density Research Articles

Role of estrogen in sex differences in memory, emotion and neuropsychiatric disorders.

Estrogen regulates a wide range of neuronal functions in the brain, such as dendritic spine formation, remodeling of synaptic plasticity, cognition, neurotransmission, and neurodevelopment. Estrogen interacts with intracellular estrogen receptors (ERs) and membrane-bound ERs to produce its effect via genomic and non-genomic pathways. Any alterations in these pathways affect the number, size, and shape of dendritic spines in neurons associated with psychiatric diseases. Increasing evidence suggests that estrogen fluctuation causes changes in dendritic spine density, morphology, and synapse numbers of excitatory and inhibitory neurons differently in males and females. In this review, we discuss the role of estrogen hormone in rodents and humans based on sex differences. First, we explain estrogen role in learning and memory and show that a high estrogen level alleviates the deficits in learning and memory. Secondly, we point out that estrogen produces a striking difference in emotional memories in men and women, which leads them to display sex-specific differences in underlying neuronal signaling. Lastly, we discuss that fluctuations in estrogen levels in men and women are related to neuropsychiatric disorders, including schizophrenia, autism spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD), bipolar disorder (BPD), major depressive disorder (MDD), substance use disorder (SUD), and anxiety disorders.

Acupuncture Alleviates Chronic Ischemic White Matter Injury in SHR Rats via JNK-NMDAR Circuit.

To study the protective mechanism of acupuncture at "Jiangya Recipe" on chronic ischemic white matter injury in spontaneously hypertensive rats (SHR) and the regulation of Jun N-terminal kinase-N-methyl-D-aspartate receptor (JNK-NMDAR) loop. A hypertensive white matter injury model was established in 46 male SHR rats aged 11 weeks by bilateral common carotid artery tapering (SHR-2VGO). In the SHR sham operation group, only bilateral common carotid arteries were isolated and in the SHR-2VGO modeling group, 36 rats were used for microcoil spring clip implantation to narrow the common carotid arteries and then, after 2 weeks of modeling, rats with impaired motor function were removed, and SHR-2VGO rats with successful final models were randomly divided into the model group, JNK blocking group, and acupuncture group. The sham operation group, model group, and JNK blocking group underwent the same grasping fixation, and the acupuncture group received acupuncture at acupoints "Jiangya Fang" once daily. In the JNK blocker group, an injection cannula was implanted into the lateral ventricle and sp600125 was injected into the lateral ventricle at 4.5 ul/day for 4 weeks. One week after the end of the intervention, white matter lesions were detected by MRI DWI and T2 imaging, and the learning and memory ability of rats was tested by Y-Maze and Passive Avoidance. Myelin density was detected by luxol fast blue (LFB) staining, also axon arrangement, myelin integrity, and thickness of neurons were detected by electron microscopy; neuronal morphology and the number of Nissl bodies in the hippocampus were detected by Nissl staining, dendritic spine density changes were detected by Golgi staining, and JNK, NMDAR1, and N-methyl-D-receptor 2B (NMDAR2B) in DG, CA3 region of hippocampus were detected by immunohistochemistry, protein expression of p-JNK/JNK, p-NMDAR1/NMDAR1, NMDAR2B, GSK3β protein expression in the fimbria of hippocampus was detected by Western blot. The Y maze test of SHR-2VGO+Acu and SHR-2VGO+ sp600125 group showed that the spontaneous alternating reaction rate increased significantly. At the same time, the incubation period increased significantly and the number of errors decreased significantly in Passive Avoidance. MRI T2WI showed that the white matter high signal of the corpus callosum, internal capsule and hippocampal fimbria in the SHR-2VGO+ sp600125 and SHR-2VGO+Acu groups was significantly lower than that in the SHR-2VGO model group, and the striatum and anterior commissure were not obvious. DWI showed that the SHR-2VGO model group had scattered high signal and limited diffusion movement in both the internal capsule and striatum, but the difference between groups was not obvious. Compared with SHR-2VGO rats, LFB staining of SHR-2VGO + sp600125 and SHR-2VGO +Acu groups showed significant relaxation of myelin porosity in corpus callosum, striatum, inner capsule, anterior commissure and hippocampal fimbria, and electron microscopy showed improved axonal myelin integrity and thickness in corpus callosum region. Also, the number of blue patchy Nissl bodies increased, and the number and complexity of dendritic spines increased significantly in Golgi staining. Immunohistochemical detection showed that JNK levels in DG and CA3 region were increased and NMDAR1 and NMDAR2B levels were decreased in SHR-2VGO+Acu and SHR-2VGO+ sp600125 groups. Meanwhile, protein expressions of GSK3β, NMDAR1/p-NMDAR1 and NMDAR2B in fimbria of hippocampus were increased, and JNK/P-JNK protein expression decreased. Acupuncture can increase the density and thickness of myelin sheath in white matter areas of corpus callosum, anterior commissure and hippocampal fimbria, increase the number and length of hippocampal neuronal dendrites, and improve hypertensive white matter injury and cognitive decline through JNK-NMDAR pathway.

A Unique Role for Protocadherin γC3 in Promoting Dendrite Arborization through an Axin1-Dependent Mechanism.

The establishment of a functional cerebral cortex depends on the proper execution of multiple developmental steps, culminating in dendritic and axonal outgrowth and the formation and maturation of synaptic connections. Dysregulation of these processes can result in improper neuronal connectivity, including that associated with various neurodevelopmental disorders. The γ-Protocadherins (γ-Pcdhs), a family of 22 distinct cell adhesion molecules that share a C-terminal cytoplasmic domain, are involved in multiple aspects of neurodevelopment including neuronal survival, dendrite arborization, and synapse development. The extent to which individual γ-Pcdh family members play unique versus common roles remains unclear. We demonstrated previously that the γ-Pcdh-C3 isoform (γC3), via its unique "variable" cytoplasmic domain (VCD), interacts in cultured cells with Axin1, a Wnt-pathway scaffold protein that regulates the differentiation and morphology of neurons. Here, we confirm that γC3 and Axin1 interact in the cortex in vivo and show that both male and female mice specifically lacking γC3 exhibit disrupted Axin1 localization to synaptic fractions, without obvious changes in dendritic spine density or morphology. However, both male and female γC3 knock-out mice exhibit severely decreased dendritic complexity of cortical pyramidal neurons that is not observed in mouse lines lacking several other γ-Pcdh isoforms. Combining knock-out with rescue constructs in cultured cortical neurons pooled from both male and female mice, we show that γC3 promotes dendritic arborization through an Axin1-dependent mechanism mediated through its VCD. Together, these data identify a novel mechanism through which γC3 uniquely regulates the formation of cortical circuitry.SIGNIFICANCE STATEMENT The complexity of a neuron's dendritic arbor is critical for its function. We showed previously that the γ-Protocadherin (γ-Pcdh) family of 22 cell adhesion molecules promotes arborization during development; it remained unclear whether individual family members played unique roles. Here, we show that one γ-Pcdh isoform, γC3, interacts in the brain with Axin1, a scaffolding protein known to influence dendrite development. A CRISPR/Cas9-generated mutant mouse line lacking γC3 (but not lines lacking other γ-Pcdhs) exhibits severely reduced dendritic complexity of cerebral cortex neurons. Using cultured γC3 knock-out neurons and a variety of rescue constructs, we confirm that the γC3 cytoplasmic domain promotes arborization through an Axin1-dependent mechanism. Thus, γ-Pcdh isoforms are not interchangeable, but rather can play unique neurodevelopmental roles.

Reduced BDNF expression in the auditory cortex contributed to neonatal pain-induced hearing impairment and dendritic pruning deficiency in mice

IntroductionProcedural pain in neonates is associated with impaired neurodevelopment. Whether hearing development is impaired, however, remains unknown. This study examined potential cause-and-effect relationship between neonatal pain and subsequent hearing loss...

A Possible Mechanism for Development of Working Memory Impairment in Male Mice Subjected to Inflammatory Pain

We studied the effects of inflammatory pain on working memory and correlated the pain effects with changes in dendritic spine density and glutamate signaling in the medial prefrontal cortex (mPFC) of male and female mice. Injection of Complete Freund’s Adjuvant (CFA) into the hind paw modeled inflammatory pain. The CFA equally decreased the mechanical thresholds in both sexes. The density of dendritic spines, as a marker for neuronal input, increased on the dendrites of both, pyramidal cells and interneurons in males but only on the dendrites of interneurons in CFA injected females. Next, we injected virus with glutamate sensor (pAAV5.hSyn.iGluSnFr) into the mPFC and used fiber photometry to record glutamate signaling during Y-maze spontaneous alternations test, which is a test for working memory in rodents. The detected fluorescent signal was higher during correct alternations when compared to incorrect alternations in both sexes. The CFA injection did not change the pattern of glutamate fluorescence during the test but the female mice made fewer incorrect alternations than their male counterparts. Furthermore, while the CFA injection decreased the expression of the glutamate transporter VGlut1 on the soma of mPFC neurons in both sexes, the decrease was sex dependent. We concluded that inflammatory pain, which increases sensory input into the mPFC neurons, may impair working memory by altering the glutamate signaling. The glutamate deficit that develops as a result of the pain is more pronounced in male mice in comparison to female mice.

PRG-1 prevents neonatal stimuli-induced persistent hyperalgesia and memory dysfunction via NSF/Glu/GluR2 signaling

SummaryNeonatal repetitive noxious stimuli (RNS) has been shown to cause long-term harmful effects on nociceptive processing, learning, and memory which persist until adulthood. Plasticity-related gene 1 (PRG-1) regulates synaptic plasticity and functional reorganization in the brain during neuronal development. In this study, neonatal RNS rats were established by repetitive needle pricks to neonatal rats on all four feet to model repetitive pain exposure in infants. Neonatal RNS caused thermal hyperalgesia, mechanical allodynia, learning, and memory impairments which manifested in young rats and persisted until adulthood. Hippocampal PRG-1/N-ethylmaleimide sensitive fusion protein (NSF) interaction was determined to be responsible for the RNS-induced impairment via enhanced extracellular glutamate release and AMPAR GluR2 trafficking deficiency in a cell-autonomous manner. These pathways likely act synergistically to cause changes in dendritic spine density. Our findings suggest that PRG-1 prevents the RNS-induced hyperalgesia, learning, and memory impairment by regulating synaptic plasticity via NSF/Glu/GluR2 signaling.

Repeated mild traumatic brain injuries in mice cause age- and sex-specific alterations in dendritic spine density

Mild traumatic brain injuries (mTBI) plague the human population and their prevalence is increasing annually. More so, repeated mTBIs (RmTBI) are known to manifest and compound neurological deficits in vulnerable populations. Age at injury and sex are two important factors influencing RmTBI pathophysiology, but we continue to know little about the specific effects of RmTBI in youth and females. In this study, we directly quantified the effects of RmTBI on adolescent and adult, male and female mice, with a closed-head lateral impact model. We report age- and sex-specific neurobehavioural deficits in motor function and working memory, microglia responses to injury, and the subsequent changes in dendritic spine density in select brain regions. Specifically, RmTBI caused increased footslips in adult male mice as assessed in a beam walk assay and significantly reduced the time spent with a novel object in adolescent male and female mice. RmTBIs caused a significant reduction in microglia density in male mice in the motor cortex, but not female mice. Finally, RmTBI significantly reduced dendritic spine density in the agranular insular cortex (a region of the prefrontal cortex in mice) and increased dendritic spine density in the adolescent male motor cortex. Together, the data provided in this study sheds new light on the heterogeneity in RmTBI-induced behavioural, glial, and neuronal architecture changes dependent on age and sex.

Changes in dendritic arborization related to the estrous cycle in pyramidal neurons of layer V of the motor cortex

Many studies on neuronal plasticity have been conducted in the hippocampus and sensory cortices. In female rats in the estrus phase, when there is a low concentration of estradiol in the blood, there is a reduction in the dendritic spine density of CA1 neurons, while an increase in dendritic spines has been observed during metestrus, when progesterone levels are high. In comparison with the hippocampus, less information is known about dendritic remodeling of the motor cortex. Thus, the objective of the present study was to evaluate the neuronal morphology of pyramidal cells of layer V of the motor cortex in each phase of the estrous cycle. For this, we used Long-Evans strain rats and formed 4 experimental groups according to the phase of the estrous cycle at the moment of sacrifice: proestrus, estrus, metestrus, or diestrus. All animals were gently monitored regarding the expression of one estrous cycle in order to determine the regularity of the cycle. We obtained the brains in order to evaluate the neuronal morphology of neurons of layer V of the primary motor cortex following the Golgi-Cox method and Sholl analysis. Our results show that the dendritic arborization of neurons of rats sacrificed in the metestrus phase is reduced compared to the other phases of the estrous cycle. However, we did not find changes in dendritic spine density between experimental groups. When comparing our results with previous data, we can suggest that estrogens and progesterone differentially promote plasticity events in pyramidal neurons between different brain regions.

Neurobehavioral alternations of the female offspring born to polycystic ovary syndrome model rats administered by Chinese herbal medicine

BackgroundChinese herbal medicine (CHM) has significant effects that improve the reproductive functions of patients with polycystic ovary syndrome (PCOS). However, the intergenerational effects of CHM on offspring and the underlying mechanism of CHM remain unclear. This study aimed to explore the effects and the underlying mechanism of CHM, specifically the Bu-Shen-Tian-Jing formula (BSTJF), on model rats with polycystic ovary syndrome (PCOS) and the neurobehavioral alterations of female offspring born to PCOS rats administered BSTJF.MethodsHigh-performance liquid chromatography-mass spectrometry (HPLC–MS) and network pharmacology analysis were performed to identify the active ingredients and potential targets of BSTJF. Moreover, PCOS model rats were used to validate the role of BSTJF in reproduction and progeny neural development and to confirm the network pharmacological targets.ResultsA total of 91 constituents were characterized from BSTJF. The 20 most significant KEGG pathways and the high-frequency genes of these pathways were predicted to be putative targets of these molecules. The rat experiment showed that the downregulation of FOS protein expression in the ovarian granulosa cells of the PCOS group was reversed by BSTJF. The target residence time of the 5-week-old female offspring of the BSTJF group was higher than that of the PCOS group in the water maze experiment. Compared to the PCOS group, the changes in dendritic spine density, ultrastructure of neurons and synapses, and Gabrb1 and Grin2b protein expression levels in the hippocampus of female offspring were partially reversed in the BSTJF group.ConclusionsBSTJF can effectively improve ovarian follicle development in PCOS rats and has positive effects on pubertal neurobehavioral alterations in the female offspring of these rats by reversing dendritic spine density, the ultrastructure of neurons and synapses, and the Gabrb1 and Grin2b protein expression levels in the hippocampus.

Dendritic spine density changes and homeostatic synaptic scaling: a meta-analysis of animal studies.

Mechanisms of homeostatic plasticity promote compensatory changes of cellular excitability in response to chronic changes in the network activity. This type of plasticity is essential for the maintenance of brain circuits and is involved in the regulation of neural regeneration and the progress of neurodegenerative disorders. One of the most studied homeostatic processes is synaptic scaling, where global synaptic adjustments take place to restore the neuronal firing rate to a physiological range by the modulation of synaptic receptors, neurotransmitters, and morphology. However, despite the comprehensive literature on the electrophysiological properties of homeostatic scaling, less is known about the structural adjustments that occur in the synapses and dendritic tree. In this study, we performed a meta-analysis of articles investigating the effects of chronic network excitation (synaptic downscaling) or inhibition (synaptic upscaling) on the dendritic spine density of neurons. Our results indicate that spine density is consistently reduced after protocols that induce synaptic scaling, independent of the intervention type. Then, we discuss the implication of our findings to the current knowledge on the morphological changes induced by homeostatic plasticity.

Editing DNA Methylation at Dendritic-Spine Associated Locus via CRISPR-dCas9

Dendritic spine density (DSD) is reduced in postmortem superior temporal gyrus (STG) of schizophrenia (SZ) subjects. DNA methylation (DNAm) may mediate lower DSD given its role in gene expression and studies of global DNAm manipulation demonstrating DSD changes. We previously found that DNAm and DSD correlated at many loci in STG of non-psychiatric control (NPC), but not SZ, subjects. Further, these DNAm-DSD correlations significantly differ between diagnoses at several dendritic spine-associated loci, particularly DLG1, which is altered in expression in SZ and is implicated in DSD regulation.

Ketamine Rapidly Enhances Glutamate-Evoked Dendritic Spinogenesis in Medial Prefrontal Cortex Through Dopaminergic Mechanisms

BackgroundKetamine elicits rapid onset antidepressant effects in patients with clinical depression through mechanisms hypothesized to involve the genesis of neocortical dendritic spines and synapses. Yet, the observed changes in dendritic spine morphology usually emerge well after ketamine clearance, raising questions about the link between rapid behavioral effects of ketamine and plasticity. MethodsHere, we used two-photon glutamate uncaging/imaging to focally induce spinogenesis in the medial prefrontal cortex, directly interrogating baseline and ketamine-associated plasticity of deep layer pyramidal neurons in C57BL/6 mice. We combined pharmacological, genetic, optogenetic, and chemogenetic manipulations to interrogate dopaminergic mechanisms underlying ketamine-induced rapid enhancement in evoked plasticity and associated behavioral changes. ResultsWe found that ketamine rapidly enhances glutamate-evoked spinogenesis in the medial prefrontal cortex, with timing that matches the onset of its behavioral efficacy and precedes changes in dendritic spine density. Ketamine increases evoked cortical spinogenesis through dopamine Drd1 receptor (Drd1) activation that requires dopamine release, compensating blunted plasticity in a learned helplessness paradigm. The enhancement in evoked spinogenesis after Drd1 activation or ketamine treatment depends on postsynaptic protein kinase A activity. Furthermore, ketamine’s behavioral effects are blocked by chemogenetic inhibition of dopamine release and mimicked by activating presynaptic dopaminergic terminals or postsynaptic Gαs-coupled cascades in the medial prefrontal cortex. ConclusionsOur findings highlight dopaminergic mediation of rapid enhancement in activity-dependent dendritic spinogenesis and behavioral effects induced by ketamine.

Dendritic Spine Remodeling and Synaptic Tau Levels in PS19 Tauopathy Mice

Synapse or dendritic spine loss is the strongest correlate of cognitive decline in Alzheimer’s disease (AD), and neurofibrillary tangles (NFTs), but not amyloid-β plaques, associate more closely with transition to mild cognitive impairment. Yet, how dendritic spine architecture is affected by hyperphosphorylated tau is still an ongoing question. To address this, we combined cell and biochemical analyses of the Tau P301S mouse line (PS19). Individual pyramidal neurons in the hippocampus and medial prefrontal cortex (mPFC) were targeted for iontophoretic microinjection of fluorescent dye, followed by high-resolution confocal microscopy and 3D morphometry analysis. In the hippocampus, PS19 mice and non-transgenic (NTG) littermates displayed equivalent spine density at 6 and 9 months, but both genotypes exhibited age-related thin spine loss. PS19 mice exhibited significant increases in synaptic tau protein levels and mean dendritic spine head diameter with age. This suggests that CA1 pyramidal neurons in PS19 mice may undergo spine remodeling in response to tau accumulation and age. In the mPFC, spine density was similar among PS19 mice and NTG littermates at 6 and 9 months, but age-related reductions in synaptic tau levels were observed among PS19 mice. Collectively, these studies reveal brain region-specific changes in dendritic spine density and morphology in response to age and the presence of hyperphosphorylated tau in the PS19 mouse line.

Sex differences in dendritic spine density and morphology in auditory and visual cortices in adolescence and adulthood

Dendritic spines are small protrusions on dendrites that endow neurons with the ability to receive and transform synaptic input. Dendritic spine number and morphology are altered as a consequence of synaptic plasticity and circuit refinement during adolescence. Dendritic spine density (DSD) is significantly different based on sex in subcortical brain regions associated with the generation of sex-specific behaviors. It is largely unknown if sex differences in DSD exist in auditory and visual brain regions and if there are sex-specific changes in DSD in these regions that occur during adolescent development. We analyzed dendritic spines in 4-week-old (P28) and 12-week-old (P84) male and female mice and found that DSD is lower in female mice due in part to fewer short stubby, long stubby and short mushroom spines. We found striking layer-specific patterns including a significant age by layer interaction and significantly decreased DSD in layer 4 from P28 to P84. Together these data support the possibility of developmental sex differences in DSD in visual and auditory regions and provide evidence of layer-specific refinement of DSD over adolescent brain development.

Effect of Phosphorylated Tau on Cortical Pyramidal Neuron Morphology during Hibernation.

The dendritic spines of pyramidal cells are the main postsynaptic target of excitatory glutamatergic synapses. Morphological alterations have been described in hippocampal dendritic spines during hibernation—a state of inactivity and metabolic depression that occurs via a transient neuronal tau hyperphosphorylation. Here, we have used the hibernating Syrian hamster to investigate the effect of hyperphosphorylated tau regarding neocortical neuronal structure. In particular, we examined layer Va pyramidal neurons. Our results indicate that hibernation does not promote significant changes in dendritic spine density. However, tau hyperphosphorylated neurons show a decrease in complexity, an increase in the tortuosity of the apical dendrites, and an increase in the diameter of the basal dendrites. Tau protein hyperphosphorylation and aggregation have been associated with loss or alterations of dendritic spines in neurodegenerative diseases, such as Alzheimer’s disease (AD). Our results may shed light on the correlation between tau hyperphosphorylation and the neuropathological processes in AD. Moreover, we observed changes in the length and area of the apical and basal dendritic spines during hibernation regardless of tau hyperphosphorylation. The morphological changes observed here also suggest region specificity, opening up debate about a possible relationship with the differential brain activity registered in these regions in previous studies.

Protein arginine methyltransferase-1 deficiency restrains depression-like behavior of mice by inhibiting inflammation and oxidative stress via Nrf-2

Current evidence indicates that depression is accompanied by the activation of inflammatory response and oxidative stress. Protein arginine methyltransferase 1 (PRMT1) is a histone methyltransferase that methylates Arg3 on histone H4, playing crucial role in regulating various pathological processes. In the study, we attempted to explore the effects of PRMT1 on animal model with depression through a single administration of lipopolysaccharide (LPS). Our results indicated that PRMT1 knockout (PRMT1−/−) improved LPS-induced anxiety- and depressive-like behavior, along with up-regulated expression levels of brain-derived neurotrophic factor (BDNF) and PSD-95. Furthermore, PRMT1 deficiency significantly improved LPS-induced changes in dendritic spine density in the areas of prefrontal cortex (PFC), CA3 and dentate gyrus (DG), and nucleus accumbens (NAc). In addition, PRMT1 deletion ameliorated the neuroinflammatory responses, as evidenced by the reduced expression of interleukin 1β (IL-1β) and tumor necrosis factor (TNF)-α, which might be through repressing nuclear factor-κB (NF-κB) signaling. Moreover, oxidative stress induced by LPS was alleviated by PRMT1 knockout in hippocampus of mice at least partly via promoting Nrf-2 expressions. The anti-depressant effects of PRMT1 inhibition were verified in LPS-incubated astrocytes. Importantly, we found that PRMT1 knockout-alleviated inflammation and oxidative stress triggered by LPS were significantly recovered by the suppression of Nrf-2. Therefore, Nrf-2 was markedly involved in PRMT1-regulated depression-like behavior. Taken together, the results indicated that PRMT1 might be an important therapeutic target for developing effective treatment to prevent depressive-like behavior.

Changes in Dendritic Spine Density and Inhibitory Perisomatic Connectivity onto Medium Spiny Neurons in l-Dopa-Induced Dyskinesia

Using bacterial artificial chromosome-double transgenic mice expressing tdTomato in D1 receptor-medium spiny neurons (MSNs) and enhanced green fluorescent protein in D2 receptor-MSNs, we have studied changes in spine density and perisomatic GABAergic boutons density in MSNs of both the D1R and D2R pathways, in an experimental model of parkinsonism (mouse injected with 6-hydroxydopamine in the medial forebrain bundle), both in the parkinsonian and dyskinetic condition induced by L-DOPA treatment. To assess changes in perisomatic GABAergic connectivity onto MSNs, we measured the number of contacts originated from parvalbumin (PV)-containing striatal "fast-spiking" interneurons (FSIs), the major component of a feed-forward inhibition mechanism that regulates spike timing in MSNs, in both cell types as well as the number of vesicular GABA transporter (VGAT) contacts. Furthermore, we determined changes in PV-immunoreactive cell density by PV immunolabeling combined with Wisteria floribunda agglutinin (WFA) labeling to detect FSI in a PV-independent manner. We also explored the differential expression of striatal activity-regulated cytoskeleton-associated protein (Arc) and c-Fos in both types of MSNs as a measure of neuronal activation. Our results confirm previous findings of major structural changes in dendritic spine density after nigrostriatal denervation, which are further modified in the dyskinetic condition. Moreover, the finding of differential modifications in perisomatic GABAergic connectivity and neuronal activation in MSNs suggests an attempt by the system to regain homeostasis after denervation and an imbalance between excitation and inhibition leading to the development of dyskinesia after exposure to L-DOPA.

Response learning stimulates dendritic spine growth on dorsal striatal medium spiny neurons.

Increases in the number and/or the size of dendritic spines, sites of excitatory synapses, have been linked to different types of learning as well as synaptic plasticity in several brain regions, including the hippocampus, sensory cortex, motor cortex, and cerebellum. By contrast, a previous study reported that training on a maze task requiring the dorsal striatum has no effect on medium spiny neuron dendritic spines in this area. These findings might suggest brain region-specific differences in levels of plasticity as well as different cellular processes underlying different types of learning. No previous studies have investigated whether dendritic spine density changes may be localized to specific subpopulations of medium spiny neurons, nor have they examined dendritic spines in rats trained on a dorsolateral striatum-dependent maze task in comparison to rats exposed to the same type of maze in the absence of training. To address these questions further, we labeled medium spiny neurons with the lipophilic dye DiI and stained for the protein product of immediate early gene zif 268, an indirect marker of neuronal activation, in both trained and untrained groups. We found a small but significant increase in dendritic spine density on medium spiny neurons of the dorsolateral striatum after short-term intensive training, along with robust increases in the density of spines with mushroom morphology coincident with reductions in the density of spines with thin morphology. However, these results were not associated with zif 268 expression. Our findings suggest that short-term intensive training on a dorsolateral striatum-dependent maze task induces rapid increases in dendritic spine density and maturation on medium spiny neurons of the dorsolateral striatum, an effect which may contribute to early acquisition of the learned response in maze training.

Neuroanatomical and electrophysiological recovery in the contralateral intact cortex following transient focal cerebral ischemia in rats

ObjectivesFocal cerebral ischemia may induce synaptic, electrophysiological, and metabolic dysfunction in remote areas. We have shown that the remote dendritic spine density changes and electrophysiological diaschisis in the acute and subacute stages after stroke previously. Here, we further evaluated electrophysiological outcomes and synapto-dendritic plasticity in long-term recovery in the contralateral cortex following focal cerebral ischemia.MethodsMale Sprague–Dawley rats were subjected to intraluminal suture occlusion for 90 min or sham-occlusion. Somatosensory electrophysiological recordings (SSEPs) and neurobehavioral tests were recorded each day for 28 days. Postmortem brains were sectioned and subjected to Nissl staining and Golgi–Cox impregnation through a 28-day period following ischemic stroke.ResultsIn the ipsilateral cortex, infarct size in the cortex and striatum was decreased after the subacute stage; the brains showed reduced swelling in the cortex and stratum 3 days after ischemic insults. Dendritic spine density and SSEP amplitude decreased significantly during a 28-day recovery period. In the contralateral cortex, dendritic spine density and SSEP amplitude decreased significantly for 21 days after ischemic stroke, but recovered to baseline by day 28. The deterioration of the dendritic spine (density reduction) in the ischemic cortex was observed; however, this increased neuroplasticity in the contralateral cortex in the subacute stage.DiscussionFocal cerebral ischemia–reperfusion induces time-dependent reduction of dendritic spine density and electrophysiological depression in both the ipsilateral and contralateral cortices and intact brain. This neuroanatomical and electrophysiological evidence suggests that neuroplasticity and functional re-organization in the contralateral cortex is possible following focal cerebral ischemia.

Cranial Irradiation Altered Dendritic Spine Complexity in the Rat Hippocampus and Induced Memory Decline

Cognitive deficit was the most serious complication of cranial irradiation. However, the underlying mechanisms remain obscure. Dendrites are the anatomic bases of synaptic contact and action potential propagation. Alterations of dendritic architecture may contribute to radiation-induced memory dysfunction. 21-day-old Sprague-Dawley rats received 10Gy cranial irradiation. 1 and 3 months later, Morris Water Maze, Fear Conditioning test and novel object recognition were used to test the memory function. Golgi staining was used to assess changes in dendritic spine density and morphology. Moreover, cytoskeletal proteins PSD-95 were analyzed with Western blot. Our data showed that 10Gy cranial irradiation induced significant decline in the spatial memory and memory retention of rats and accompanied the morphological changes in dendritic spines. The result revealed significant reductions in spine density at 1 month (40.58%) and 3 months (28.92%) in the DG. In CA1 basal dendrites, irradiation resulted in a significant reduction (33.29%) in spine density only at 1month postirradiation. Compared to control, mushroom spines reduced at 1 month (7.17%, 10.01%) and 3 months (9.29%, 11.94%) post irradiation in DG and CA1 basal dendrites, respectively. Also, we found PSD-95 depletion coincided in time with alteration in dendritic spines. These data suggest that cranial irradiation decreased the dendritic spine density and mushroom spines, which may be associated with radiation-induced memory dysfunction. Acknowledgment: This study was supported by the National Natural Science Foundation of China 81402517 and the Suzhou Science and Technology Project SYS201651.