Changes In Dendritic Spines Research Articles

Donepezil Reverses Dendritic Spine Morphology Adaptations and Fmr1 Epigenetic Modifications in Hippocampus of Adult Rats After Adolescent Alcohol Exposure.

Adolescent intermittent ethanol (AIE) exposure produces persistent impairments in cholinergic and epigenetic signaling and alters markers of synapses in the hippocampal formation, effects that are thought to drive hippocampal dysfunction in adult rodents. Donepezil (Aricept), a cholinesterase inhibitor, is used clinically to ameliorate memory-related cognitive deficits. Given that donepezil also prevents morphological impairment in preclinical models of neuropsychiatric disorders, we investigated the ability of donepezil to reverse morphological and epigenetic adaptations in the hippocampus of adult rats exposed to AIE. Because of the known relationship between dendritic spine density and morphology with the fragile X mental retardation 1 (Fmr1) gene, we also assessed Fmr1 expression and its epigenetic regulation in hippocampus after AIE and donepezil pretreatment. Adolescent rats were administered intermittent ethanol for 16days starting on postnatal day 30. Rats were treated with donepezil (2.5mg/kg) once a day for 4 days starting 20days after the completion of AIE exposure. Brains were dissected out after the fourth donepezil dose, and spine analysis was completed in dentate gyrus granule neurons. A separate cohort of rats, treated identically, was used for molecular studies. AIE exposure significantly reduced dendritic spine density and altered morphological characteristics of subclasses of dendritic spines. AIE exposure also increased mRNA levels and H3-K27 acetylation occupancy of the Fmr1 gene in hippocampus. Treatment of AIE-exposed adult rats with donepezil reversed both the dendritic spine adaptations and epigenetic modifications and expression of Fmr1. These findings indicate that AIE produces long-lasting decreases in dendritic spine density and changes in Fmr1 gene expression in the hippocampal formation, suggesting morphological and epigenetic mechanisms underlying previously reported behavioral deficits after AIE. The reversal of these effects by subchronic, post-AIE donepezil treatment indicates that these AIE effects can be reversed by up-regulating cholinergic function.

Role of α7nAChR-NMDAR in sevoflurane-induced memory deficits in the developing rat hippocampus.

Detrimental effects of volatile anaesthetics, including sevoflurane, on the structure and function of the developing brain have been reported. The internalization of N-methyl-D-aspartate receptors (NMDARs) contributes to anaesthetic neurotoxicity. Both nicotinic acetylcholine receptors (nAChRs) and NMDAR play a critical role in the development of the nervous system. Moreover, nAChR can interact with NMDAR, and previous studies have demonstrated modulation of NMDAR by nAChR. In our study, we used an α7 nicotinic acetylcholine receptor (α7nAChR) agonist and α7nAChR antagonist to explore the role of α7nAChR and NMDAR in sevoflurane-induced long-term effects on memory and dendritic spine both in vivo and in vitro. The results revealed that the activation of α7nAChR attenuated the development of sevoflurane-induced memory deficit and dendritic spine changes, which might be by regulating NR2B-containing NMDAR trafficking from the intracellular pool to the cell surface pool in the hippocampus. Moreover, we demonstrated that α7nAChR could regulate NR2B-containing NMDAR via Src-family tyrosine kinase (SFK). Thus, our current study indicates that the trafficking of NR2B-containing NMDAR is regulated by α7nAChR via SFK in neonatal rat hippocampus, which may be secondary to sevoflurane-induced cognitive deficits in the developing hippocampus.

The polarity protein Angiomotin p130 controls dendritic spine maturation.

The actin cytoskeleton is essential for the structural changes in dendritic spines that lead to the formation of new synapses. Although the molecular mechanisms underlying spine formation are well characterized, the events that drive spine maturation during development are largely unknown. In this study, we demonstrate that Angiomotin (AMOT-130) is necessary for spine stabilization. AMOT-130 is enriched in mature dendritic spines and functions to stabilize the actin cytoskeleton by coupling F-actin to postsynaptic protein scaffolds. These functions of AMOT are transiently restricted during postnatal development by phosphorylation imposed by the kinase Lats1. Our study proposes that AMOT-130 is essential for normal spine morphogenesis and identifies Lats1 as an upstream regulator in this process. Moreover, our findings may link AMOT-130 loss and the related spine defects to neurological disorders.

MiR-134 modulates chronic stress-induced structural plasticity and depression-like behaviors via downregulation of Limk1/cofilin signaling in rats

Increasing evidence has suggested that depression is a neuropsychiatric condition associated with neuroplasticity within specific brain regions. However, the mechanisms by which neuroplasticity exerts its effects in depression remain largely uncharacterized. In the present study we show that chronic stress effectively induces depression-like behaviors in rats, an effect which was associated with structural changes in dendritic spines and synapse abnormalities within neurons of the ventromedial prefrontal cortex (vmPFC). Moreover, unpredictable chronic mild stress (UCMS) exposure significantly increased the expression of miR-134 within the vmPFC, an effect which was paralleled with a decrease in the levels of expression and phosphorylation of the synapse-associated proteins, LIM-domain kinase 1 (Limk1) and cofilin. An intracerebral infusion of the adenovirus associated virus (AAV)-miR-134-sponge into the vmPFC of stressed rats, which blocks mir-134 function, significantly ameliorated neuronal structural abnormalities, biochemical changes and depression-like behaviors. Chronic administration of ginsenoside Rg1 (40 mg/kg, 5 weeks), a potential neuroprotective agent extracted from ginseng, significantly ameliorated the behavioral and biochemical changes induced by UCMS exposure. These results suggest that miR-134-mediated dysregulation of structural plasticity may be related to the display of depression-like behaviors in stressed rats. The neuroprotective effects of ginsenoside Rg1, which produces an antidepressant like effect in this model of depression, appears to result from modulation of the miR-134 signaling pathway within the vmPFC.

Synaptic aging disrupts synaptic morphology and function in cerebellar Purkinje cells

Synapses are key structures in neural networks, and are involved in learning and memory in the central nervous system. Investigating synaptogenesis and synaptic aging is important in understanding neural development and neural degeneration in diseases such as Alzheimer disease and Parkinson's disease. Our previous study found that synaptogenesis and synaptic maturation were harmonized with brain development and maturation. However, synaptic damage and loss in the aging cerebellum are not well understood. This study was designed to investigate the occurrence of synaptic aging in the cerebellum by observing the ultrastructural changes of dendritic spines and synapses in cerebellar Purkinje cells of aging mice. Immunocytochemistry, DiI diolistic assays, and transmission electron microscopy were used to visualize the morphological characteristics of synaptic buttons, dendritic spines and synapses of Purkinje cells in mice at various ages. With synaptic aging in the cerebellum, dendritic spines and synaptic buttons were lost, and the synaptic ultrastructure was altered, including a reduction in the number of synaptic vesicles and mitochondria in presynaptic termini and smaller thin specialized zones in pre- and post-synaptic membranes. These findings confirm that synaptic morphology and function is disrupted in aging synapses, which may be an important pathological cause of neurodegenerative diseases.

Pathophysiological Bases of Comorbidity: Traumatic Brain Injury and Post-Traumatic Stress Disorder

The high rates of traumatic brain injury (TBI) and post-traumatic stress disorder (PTSD) diagnoses encountered in recent years by the United States Veterans Affairs Healthcare System have increased public awareness and research investigation into these conditions. In this review, we analyze the neural mechanisms underlying the TBI/PTSD comorbidity. TBI and PTSD present with common neuropsychiatric symptoms including anxiety, irritability, insomnia, personality changes, and memory problems, and this overlap complicates diagnostic differentiation. Interestingly, both TBI and PTSD can be produced by overlapping pathophysiological changes that disrupt neural connections termed the "connectome." The neural disruptions shared by PTSD and TBI and the comorbid condition include asymmetrical white matter tract abnormalities and gray matter changes in the basolateral amygdala, hippocampus, and prefrontal cortex. These neural circuitry dysfunctions result in behavioral changes that include executive function and memory impairments, fear retention, fear extinction deficiencies, and other disturbances. Pathophysiological etiologies can be identified using experimental models of TBI, such as fluid percussion or blast injuries, and for PTSD, using models of fear conditioning, retention, and extinction. In both TBI and PTSD, there are discernible signs of neuroinflammation, excitotoxicity, and oxidative damage. These disturbances produce neuronal death and degeneration, axonal injury, and dendritic spine dysregulation and changes in neuronal morphology. In laboratory studies, various forms of pharmacological or psychological treatments are capable of reversing these detrimental processes and promoting axonal repair, dendritic remodeling, and neurocircuitry reorganization, resulting in behavioral and cognitive functional enhancements. Based on these mechanisms, novel neurorestorative therapeutics using anti-inflammatory, antioxidant, and anticonvulsant agents may promote better outcomes for comorbid TBI and PTSD.

Motor Areas Show Altered Dendritic Structure in an Amyotrophic Lateral Sclerosis Mouse Model.

Objective: Motor neurons (MNs) die in amyotrophic lateral sclerosis (ALS), a clinically heterogeneous neurodegenerative disease of unknown etiology. In human or rodent studies, MN loss is preceded by increased excitability. As increased neuronal excitability correlates with structural changes in dendritic arbors and spines, we have examined longitudinal changes in dendritic structure in vulnerable neuron populations in a mouse model of familial ALS.Methods: We used a modified Golgi-Cox staining method to determine the progressive changes in dendritic structure of hippocampal CA1 pyramidal neurons, striatal medium spiny neurons, and resistant (trochlear, IV) or susceptible (hypoglossal, XII; lumbar) MNs from brainstem and spinal cord of mice over-expressing the human SOD1G93A (SOD1) mutation, in comparison to wild-type (WT) mice, at four postnatal (P) ages of 8–15, 28–35, 65–75, and 120 days.Results: In SOD1 mice, dendritic changes occur at pre-symptomatic ages in both XII and spinal cord lumbar MNs. Spine loss without dendritic changes was present in striatal neurons from disease onset. Spine density increases were present at all ages studied in SOD1 XII MNs. Spine density increased in neonatal lumbar MNs, before decreasing to control levels by P28-35 and was decreased by P120. SOD1 XII MNs and lumbar MNs, but not trochlear MNs showed vacuolization from the same time-points. Trochlear MN dendrites were unchanged.Interpretation: Dendritic structure and spine alterations correlate with the neuro-motor phenotype in ALS and with cognitive and extra-motor symptoms seen in patients. Prominent early changes in dendritic arbors and spines occur in susceptible cranial and spinal cord MNs, but are absent in MNs resistant to loss in ALS.

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.

Dendritic spines provide cognitive resilience against Alzheimer's disease.

Neuroimaging and other biomarker assays suggest that the pathological processes of Alzheimer's disease (AD) begin years prior to clinical dementia onset. However, some 30 to 50% of older individuals who harbor AD pathology do not become symptomatic in their lifetime. It is hypothesized that such individuals exhibit cognitive resilience that protects against AD dementia. We hypothesized that in cases with AD pathology, structural changes in dendritic spines would distinguish individuals who had or did not have clinical dementia. We compared dendritic spines within layer II and III pyramidal neuron dendrites in Brodmann area 46 dorsolateral prefrontal cortex using the Golgi-Cox technique in 12 age-matched pathology-free controls, 8 controls with AD pathology (CAD), and 21 AD cases. We used highly optimized methods to trace impregnated dendrites from bright-field microscopy images that enabled accurate 3-dimensional digital reconstruction of dendritic structure for morphologic analyses. Spine density was similar among control and CAD cases but was reduced significantly in AD. Thin and mushroom spines were reduced significantly in AD compared to CAD brains, whereas stubby spine density was decreased significantly in CAD and AD compared to controls. Increased spine extent distinguished CAD cases from controls and AD. Linear regression analysis of all cases indicated that spine density was not associated with neuritic plaque score but did display negative correlation with Braak staging. These observations provide cellular evidence to support the hypothesis that dendritic spine plasticity is a mechanism of cognitive resilience that protects older individuals with AD pathology from developing dementia. Ann Neurol 2017;82:602-614.

Effects of cranial irradiation on dendritic spine complexity in the rat hippocampus and to induce memory decline.

e13545 Background: Cognitive deficit was the most serious complication of cranial irradiation in brain metastatic carcinoma. 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. Methods: 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. Results: 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. Conclusions: 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.

Synaptic Remodeling Depends on Signaling between Serotonin Receptors and the Extracellular Matrix

Rewiring of synaptic circuitry pertinent to memory formation has been associated with morphological changes in dendritic spines and with extracellular matrix (ECM) remodeling. Here, we mechanistically link these processes by uncovering a signaling pathway involving the serotonin 5-HT7 receptor (5-HT7R), matrix metalloproteinase 9 (MMP-9), the hyaluronan receptor CD44, and the small GTPase Cdc42. We highlight a physical interaction between 5-HT7R and CD44 (identified as an MMP-9 substrate in neurons) and find that 5-HT7R stimulation increases local MMP-9 activity, triggering dendritic spine remodeling, synaptic pruning, and impairment of long-term potentiation (LTP). The underlying molecular machinery involves 5-HT7R-mediated activation of MMP-9, which leads to CD44 cleavage followed by Cdc42 activation. One important physiological consequence of this interaction includes an increase in neuronal outgrowth and elongation of dendritic spines, which might have a positive effect on complex neuronal processes (e.g., reversal learning and neuronal regeneration).

Wortmannin Attenuates Seizure-Induced Hyperactive PI3K/Akt/mTOR Signaling, Impaired Memory, and Spine Dysmorphology in Rats.

Numerous studies have shown epilepsy-associated cognitive deficits, but less is known about the effects of one single generalized seizure. Recent studies demonstrate that a single, self-limited seizure can result in memory deficits and induces hyperactive phosphoinositide 3-kinase/Akt (protein kinase B)/mechanistic target of rapamycin (PI3K/Akt/mTOR) signaling. However, the effect of a single seizure on subcellular structures such as dendritic spines and the role of aberrant PI3K/Akt/mTOR signaling in these seizure-induced changes are unclear. Using the pentylenetetrazole (PTZ) model, we induced a single generalized seizure in rats and: (1) further characterized short- and long-term hippocampal and amygdala-dependent memory deficits, (2) evaluated whether there are changes in dendritic spines, and (3) determined whether inhibiting hyperactive PI3K/Akt/mTOR signaling rescued these alterations. Using the PI3K inhibitor wortmannin (Wort), we partially rescued short- and long-term memory deficits and altered spine morphology. These studies provide evidence that pathological PI3K/Akt/mTOR signaling plays a role in seizure-induced memory deficits as well as aberrant spine morphology.

Morphological dendritic spine changes of medium spiny neurons in the nucleus accumbens in 6-hydroxydopamine-lesioned rats treated with levodopa

The mechanisms of dopamine dysregulation syndrome (DDS) in Parkinson’s disease (PD) remain unclear, although it is known that the nucleus accumbens (NAc) plays a role in its development. Based on the hypothesis that DDS and levodopa-induced dyskinesia (LID) share a pathophysiological basis, we investigated dendritic spine morphology of medium spiny neurons (MSNs) in the NAc of a rat model of LID, because spine enlargement in MSNs of the caudate/putamen has been proposed to be a morphological hallmark of LID. Spines of NAc MSNs also became enlarged in the LID model. This result suggests that excitatory supersensitivity of MSNs in the NAc is involved in the development of DDS, similar to what occurs in the caudate/putamen in LID.

Neuroplasticity of Supraspinal Structures Associated with Pathological Pain.

Peripheral nerve and spinal cord injuries, along with other painful syndromes such as fibromyalgia, diabetic neuropathy, chemotherapeutic neuropathy, trigeminal neuralgia, complex regional pain syndrome, and/or irritable bowel syndrome, cause several neuroplasticity changes in the nervous system along its entire axis affecting the different neuronal nuclei. This paper reviews these changes, focusing on the supraspinal structures that are involved in the modulation and processing of pain, including the periaqueductal gray matter, red nucleus, locus coeruleus, rostral ventromedial medulla, thalamus, hypothalamus, basal ganglia, cerebellum, habenula, primary, and secondary somatosensory cortex, motor cortex, mammillary bodies, hippocampus, septum, amygdala, cingulated, and prefrontal cortex. Hyperexcitability caused by the modification of postsynaptic receptor expression, central sensitization, and potentiation of presynaptic delivery of neurotransmitters, as well as the reduction of inhibitory inputs, changes in dendritic spine, neural circuit remodeling, alteration of gray matter, and upregulation of proinflammatory mediators (e.g., cytokines) by reactivation of astrocytes and microglial cells are the main functional, structural, and molecular neuroplasticity changes observed in the above supraspinal structures, associated with pathological pain. Studying these changes in greater depth may lead to the implementation and improvement of new therapeutic strategies against pathological pain. Anat Rec, 300:1481-1501, 2017. © 2017 Wiley Periodicals, Inc.

The role of drebrin in dendritic spines.

Dendritic spines form typical excitatory synapses in the brain and their shapes vary depending on synaptic inputs. It has been suggested that the morphological changes of dendritic spines play an important role in synaptic plasticity. Dendritic spines contain a high concentration of actin, which has a central role in supporting cell motility, and polymerization of actin filaments (F-actin) is most likely involved in spine shape changes. Drebrin is an actin-binding protein that forms stable F-actin and is highly accumulated within dendritic spines. Drebrin has two isoforms, embryonic-type drebrin E and adult-type drebrin A, that change during development from E to A. Inhibition of drebrin A expression results in a delay of synapse formation and inhibition of postsynaptic protein accumulation, suggesting that drebrin A has an important role in spine maturation. In mature synapses, glutamate stimulation induces rapid spine-head enlargement during long-term potentiation (LTP) formation. LTP stimulation induces Ca2+ entry through N-methyl-d-aspartate (NMDA) receptors, which causes drebrin exodus from dendritic spines. Once drebrin exits from dendritic spine heads, the dynamic actin pool increases in spine heads to facilitate F-actin polymerization. To maintain enlarged spine heads, drebrin-decorated F-actin is thought to reform within the spine heads. Thus, drebrin plays a pivotal role in spine plasticity through regulation of F-actin.

Effects of Hippocampal LIMK Inhibition on Memory Acquisition, Consolidation, Retrieval, Reconsolidation, and Extinction.

Long-lasting changes in dendritic spines provide a physical correlate for memory formation and persistence. LIM kinase (LIMK) plays a critical role in orchestrating dendritic actin dynamics during memory processing, since it is the convergent downstream target of both the Rac1/PAK and RhoA/ROCK pathways that in turn induce cofilin phosphorylation and prevent depolymerization of actin filaments. Here, using a potent LIMK inhibitor (BMS-5), we investigated the role of LIMK activity in the dorsal hippocampus during contextual fear memory in rats. We first found that post-training administration of BMS-5 impaired memory consolidation in a dose-dependent manner. Inhibiting LIMK before training also disrupted memory acquisition. We then demonstrated that hippocampal LIMK activity seems to be critical for memory retrieval and reconsolidation, since both processes were impaired by BMS-5 treatment. Contextual fear memory extinction, however, was not sensitive to the same treatment. In conclusion, our findings demonstrate that hippocampal LIMK activity plays an important role in memory acquisition, consolidation, retrieval, and reconsolidation during contextual fear conditioning.

Synaptic Plasticity, Metaplasticity and Depression.

The development of a persistent depressive affective state has for some time been thought to result from persistent alterations in neurotransmitter-mediated synaptic transmission. While the identity of those transmitters has changed over the years, the literature has lacked mechanistic connections between the neurophysiological mechanisms they regulate, and how these mechanisms alter neuronal function, and, hence, affective homeostasis. This review will examine recent work that suggests that both long-term activity-dependent changes in synaptic strength (“plasticity”), and shifting set points for the ease of induction of future long-term changes (“metaplasticity”), may be critical to establishing and reversing a depressive behavioral state. Activity-dependent long-term synaptic plasticity involves both strengthening and weakening of synaptic connections associated with a dizzying array of neurochemical alterations that include synaptic insertion and removal of a number of subtypes of AMPA, NMDA and metabotropic glutamate receptors, changes in presynaptic glutamate release, and structural changes in dendritic spines. Cellular mechanisms of metaplasticity are far less well understood. Here, we will review the growing evidence that long-term synaptic changes in glutamatergic transmission, in brain regions that regulate mood, are key determinants of affective homeostasis and therapeutic targets with immense potential for drug development.

7th ISN special neurochemistry conference 'Synaptic function and dysfunction in brain diseases'.

This article is part of a mini review series: "Synaptic Function and Dysfunction in Brain Diseases".

Prophylactic effects of sulforaphane on depression-like behavior and dendritic changes in mice after inflammation

Inflammation plays a role in the pathophysiology of depression. Sulforaphane (SFN), an isothiocyanate compound derived from broccoli, is a potent activator of the NF-E2-related factor-2 (Nrf2), which plays a role in inflammation. In this study, we examined whether the prevention effects of SFN in lipopolysaccharide (LPS) induced depression-like behavior in mice. Pretreatment with SFN significantly blocked an increase in the serum tumor necrosis factor-α (TNF-α) level and an increase in microglial activation of brain regions after a single administration of LPS (0.5 mg/kg). Furthermore, SFN significantly potentiated increased serum levels of IL-10 after LPS administration. In the tail-suspension test and forced swimming test, SFN significantly attenuated an increase of the immobility time after LPS administration. In addition, SFN significantly recovered to control levels for LPS-induced alterations in the proteins such as brain-derived neurotrophic factor, postsynaptic density protein 95 and AMPA receptor 1 (GluA1) and dendritic spine density in the brain regions. Finally, dietary intake of 0.1% glucoraphanin (a glucosinolate precursor of SFN) food during the juvenile and adolescence could prevent the onset of LPS-induced depression-like behaviors and dendritic spine changes in the brain regions at adulthood. In conclusion, these findings suggest that dietary intake of SFN-rich broccoli sprout has prophylactic effects on inflammation-related depressive symptoms. Therefore, supplementation of SFN-rich broccoli sprout could be prophylactic vegetable to prevent or minimize the relapse by inflammation in the remission state of depressed patients.

Structural and functional plasticity of dendritic spines - root or result of behavior?

Dendritic spines are multifunctional integrative units of the nervous system and are highly diverse and dynamic in nature. Both internal and external stimuli influence dendritic spine density and morphology on the order of minutes. It is clear that the structural plasticity of dendritic spines is related to changes in synaptic efficacy, learning and memory and other cognitive processes. However, it is currently unclear whether structural changes in dendritic spines are primary instigators of changes in specific behaviors, a consequence of behavioral changes, or both. In this review, we first examine the basic structure and function of dendritic spines in the brain, as well as laboratory methods to characterize and quantify morphological changes in dendritic spines. We then discuss the existing literature on the temporal and functional relationship between changes in dendritic spines in specific brain regions and changes in specific behaviors mediated by those regions. Although technological advancements have allowed us to better understand the functional relevance of structural changes in dendritic spines that are influenced by environmental stimuli, the role of spine dynamics as an underlying driver or consequence of behavior still remains elusive. We conclude that while it is likely that structural changes in dendritic spines are both instigators and results of behavioral changes, improved research tools and methods are needed to experimentally and directly manipulate spine dynamics in order to more empirically delineate the relationship between spine structure and behavior.