Spine Elongation Research Articles

Splice variants of the CaV1.3 L-type calcium channel regulate dendritic spine morphology.

Dendritic spines are the postsynaptic compartments of glutamatergic synapses in the brain. Their number and shape are subject to change in synaptic plasticity and neurological disorders including autism spectrum disorders and Parkinson’s disease. The L-type calcium channel CaV1.3 constitutes an important calcium entry pathway implicated in the regulation of spine morphology. Here we investigated the importance of full-length CaV1.3L and two C-terminally truncated splice variants (CaV1.342A and CaV1.343S) and their modulation by densin-180 and shank1b for the morphology of dendritic spines of cultured hippocampal neurons. Live-cell immunofluorescence and super-resolution microscopy of epitope-tagged CaV1.3L revealed its localization at the base-, neck-, and head-region of dendritic spines. Expression of the short splice variants or deletion of the C-terminal PDZ-binding motif in CaV1.3L induced aberrant dendritic spine elongation. Similar morphological alterations were induced by co-expression of densin-180 or shank1b with CaV1.3L and correlated with increased CaV1.3 currents and dendritic calcium signals in transfected neurons. Together, our findings suggest a key role of CaV1.3 in regulating dendritic spine structure. Under physiological conditions it may contribute to the structural plasticity of glutamatergic synapses. Conversely, altered regulation of CaV1.3 channels may provide an important mechanism in the development of postsynaptic aberrations associated with neurodegenerative disorders.

Multiple inducers in aquatic foodwebs: Counter-measures and vulnerability to exotics

Do aquatic predator and prey species interact strongly enough to foster specialized coevolutionary feedbacks, or are interactions strongly asymmetrical, with prey species responding much more strongly and to multiple threats? Here we utilize prey induction to measure the strength of interactions around a reciprocal “arms race” candidate (Epischura-Bosmina). When prey (Bosmina) are transferred from predator-poor to predator-rich environments, defensive spines increase in length to achieve a plateau after 12–16 d (1–2 generations). Spine lengths are reversible with predator addition and removal, confirming developmental induction as the major short-term response. Laboratory assays reveal major geographic variation, implying active evolution. Responses range from almost no spine elongation where Epischura is historically absent (Europe), to major elongation where the predator and prey are in prolonged contact (Laurentian Great Lakes). Trade-offs (i.e., loss of competitive ability) can be related to spine lengths of the prey species. However, induction is not exclusive to Epischura, as a collection of invertebrate predators also induce spine elongation. Bosmina responses to individual predator species are different, implying active recognition of multiple predation threats in nature. The absence of induction responses to some exotics (e.g., Bythotrephes) may help explain disproportionate food web impacts. Both revelations underscore the importance of ongoing evolution in aquatic communities.

Actinin-4 Governs Dendritic Spine Dynamics and Promotes Their Remodeling by Metabotropic Glutamate Receptors

Dendritic spines are dynamic, actin-rich protrusions in neurons that undergo remodeling during neuronal development and activity-dependent plasticity within the central nervous system. Although group 1 metabotropic glutamate receptors (mGluRs) are critical for spine remodeling under physiopathological conditions, the molecular components linking receptor activity to structural plasticity remain unknown. Here we identify a Ca(2+)-sensitive actin-binding protein, α-actinin-4, as a novel group 1 mGluR-interacting partner that orchestrates spine dynamics and morphogenesis in primary neurons. Functional silencing of α-actinin-4 abolished spine elongation and turnover stimulated by group 1 mGluRs despite intact surface receptor expression and downstream ERK1/2 signaling. This function of α-actinin-4 in spine dynamics was underscored by gain-of-function phenotypes in untreated neurons. Here α-actinin-4 induced spine head enlargement, a morphological change requiring the C-terminal domain of α-actinin-4 that binds to CaMKII, an interaction we showed to be regulated by group 1 mGluR activation. Our data provide mechanistic insights into spine remodeling by metabotropic signaling and identify α-actinin-4 as a critical effector of structural plasticity within neurons.

Functional and structural deficits at accumbens synapses in a mouse model of Fragile X.

Fragile X is the most common cause of inherited intellectual disability and a leading cause of autism. The disease is caused by mutation of a single X-linked gene called fmr1 that codes for the Fragile X mental retardation protein (FMRP), a 71 kDa protein, which acts mainly as a translation inhibitor. Fragile X patients suffer from cognitive and emotional deficits that coincide with abnormalities in dendritic spines. Changes in spine morphology are often associated with altered excitatory transmission and long-term plasticity, the most prominent deficit in fmr1-/y mice. The nucleus accumbens, a central part of the mesocortico-limbic reward pathway, is now considered as a core structure in the control of social behaviors. Although the socio-affective impairments observed in Fragile X suggest dysfunctions in the accumbens, the impact of the lack of FMRP on accumbal synapses has scarcely been studied. Here we report for the first time a new spike timing-dependent plasticity paradigm that reliably triggers NMDAR-dependent long-term potentiation (LTP) of excitatory afferent inputs of medium spiny neurons (MSN) in the nucleus accumbens core region. Notably, we discovered that this LTP was completely absent in fmr1-/y mice. In the fmr1-/y accumbens intrinsic membrane properties of MSNs and basal excitatory neurotransmission remained intact in the fmr1-/y accumbens but the deficit in LTP was accompanied by an increase in evoked AMPA/NMDA ratio and a concomitant reduction of spontaneous NMDAR-mediated currents. In agreement with these physiological findings, we found significantly more filopodial spines in fmr1-/y mice by using an ultrastructural electron microscopic analysis of accumbens core medium spiny neuron spines. Surprisingly, spine elongation was specifically due to the longer longitudinal axis and larger area of spine necks, whereas spine head morphology and postsynaptic density size on spine heads remained unaffected in the fmr1-/y accumbens. These findings together reveal new structural and functional synaptic deficits in Fragile X.

7, 8-Dihydroxyflavone induces synapse expression of AMPA GluA1 and ameliorates cognitive and spine abnormalities in a mouse model of fragile X syndrome

Fragile X syndrome (FXS) is characterized by immature dendritic spine architectures and cognitive impairment. 7, 8-Dihydroxyflavone (7, 8-DHF) has recently been identified as a high affinity tropomyosin receptor kinase B (TrkB) agonist. The purpose of this paper was to examine the utility of 7, 8-DHF as an effective pharmacotherapeutic agent that targets dendritic pathology and cognitive impairments in FXS mutant. We synthesized pharmacologic, behavioral, and biochemical approaches to examine the effects of 7, 8-DHF on spatial and fear memory functions, and morphological spine abnormalities in fragile X mental retardation 1 (Fmr1) gene knock-out mice. The study found that 4 weeks of treatment with 7, 8-DHF improved spatial and fear memory, and ameliorated morphological spine abnormalities including the number and elongation of spines in the hippocampus and amygdala. Further mechanism analysis revealed that 7, 8-DHF enhanced the expression of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) GluA1 receptor, but reduced the normal levels of GluA2 at the synapses in Fmr1. Potentially related to drug-induced changes in AMPA receptor subunits, 7, 8-DHF at the synapses led to phosphorylation of specific serine sites on subunits Ser818 and Ser813 of GluA1, and Ser880 of GluA2, as well as phosphorylation of TrkB, calcium/calmodulin-dependent protein kinase II, and protein kinase C. However, 7, 8-DHF neither affected behavioral performance nor increased TrkB phosphorylation in WT mice, which suggested that it had FXS-specific correcting effect. Altogether, these results demonstrated that 7, 8-DHF improved learning and memory, and reduced abnormalities in spine morphology, thus providing a potential pharmacotherapeutic strategy for FXS.

Three new species of Trimma (Pisces; Gobioidei) from Indonesia.

Three new species of Trimma are described from various localities in Indonesia. All three can be readily identified from their live, freshly collected, or preserved colouration. Trimma meranyx n. sp. is further distinguished from other species by the possession of 8-9 scales in the predorsal midline, up to three rows of (usually) cycloid scales on the opercle, two scales at the posterodorsal border of the cheek, a very slightly elongate second dorsal spine which only just reaches the spine or anterior rays of the second dorsal fin, unbranched pectoral fin rays, a fifth pelvic fin ray that branches once and is 64-85% the length of the fourth ray, and a full basal membrane connecting the inner branches of the two fifth pelvic rays. The dark red (live) or black posterior half of the caudal peduncle with large white spots straddling the dorsal and ventral midlines just anterior to the first procurrent caudal fin rays is the diagnostic colour character. The species is known from North Sulawesi, West Papua (Raja Ampat and Fakfak), and the south-eastern tip of Papua New Guinea, with possible records from the Philippines and Vanuatu. Trimma pajama n. sp. has 6 scales in the predorsal midline, two ctenoid scales along the dorsal margin of the opercle, a slightly elongate second dorsal spine reaching posteriorly to the base of the spine or first ray of the second dorsal fin, unbranched pectoral fin rays, a fifth pelvic ray with a single branch point and which is 58-72% the length of the fourth ray, and a full basal membrane connecting the inner branches of the two fifth pelvic rays. The live, freshly collected and preserved colour pattern of alternating dark and light stripes on the head and most of the body (except the posterior half of the caudal peduncle) is diagnostic. It is currently known from West Papua (Raja Ampat and Fakfak) and the southern tip of Papua New Guinea, with possible records from Kalimantan (Indonesia), Palau, the Hermit Is (Papua New Guinea) and the Solomon Islands. Trimma zurae n. sp. has 8-9 scales in the predorsal midline, usually a single row of cycloid scales along the upper border of the opercle, 11 anterior and 9 posterior transverse scale rows, no elongated spines in the first dorsal fin, 9 dorsal and 8 anal fin rays, the middle rays of the pectoral fin branched, a single branch in the fifth pelvic fin ray which is 65-76% the length of the fourth ray and a reduced basal membrane of < 20% the length of the fifth ray. The eye-diameter sized black ocellated spot between the first to fifth spines of the first dorsal fin is diagnostic, as are the pupil-diameter sized orange spots on the nape, opercle and posterodorsal part of the cheek. It is currently known only from a single locality just west of Manado, Sulawesi.

Sternarchella calhamazonn. sp., the Amazon's Most Abundant Species of Apteronotid Electric Fish, with a Note on the Taxonomic Status ofSternarchus capanemaeSteindachner, 1868 (Gymnotiformes, Apteronotidae)

A new species of apteronotid electric fish is described from the Brazilian and Peruvian Amazon. Sternarchella calhamazon sp. n. conspicuously differs from its congeners in caudal peduncle shape, electric organ size and shape, hemal spine elongation above the anal fin, and arrangement of intermuscular bones adjacent to the electric organ. Sternarchella calhamazon is among the most common gymnotiform species living in the principal channels of the lowland Amazon River and its large tributaries.The nominal apteronotid Sternarchus capanemae Steindachner is an earlier published, objective synonym of Sternarchella schotti Steindachner, both names appearing in 1868. Because S. capanemae was never used as a valid name after its first use, it should be considered a nomen oblitum and Sternarchella schotti should be considered a nomen protectum and the valid name of this species.

Effects of an Ostracod (Cypris pubera) on the Rotifer Keratella tropica: Predation and Reduced Spine Development

AbstractThis study investigates two different effects of an ostracod on a rotifer. The rotifer Keratella tropica and the ostracod Cypris pubera were cultured on the alga Cryptomonas erosa. Adult ostracods (2.2 mm body length) significantly reduced the population growth rate (r day–1) of K. tropica from 0.42 to 0.13. Individuals of this size ingested live rotifers and produced fecal pellets with rotifer loricas. Smaller ostracods (both 0.59 and 1.61 mm body lengths) did not affect K. tropica 's population growth rate. Surprisingly, C. pubera significantly inhibited spine development in K. tropica. Rotifers cultured with juvenile, non‐predatory ostracods had similar lorica lengths but right and left posterior spines that were 10 and 30% shorter, respectively. The spine reduction induced by the ostracod kairomone is in striking contrast to the spine elongation induced in this rotifer by kairomones from copepods, cladocerans and Asplanchna. In shallow ecosystems, large ostracods that swim in the plankton may be important predators of rotifers. In addition, the presence of ostracods in plankton communities may be one of many factors affecting rotifer spine development. (© 2012 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)

Analysis of neurological deficits complications in the treatment of spinal deformity with posterior spinal osteotomy

To investigate the incidence and causes of neurologic deficits complications in the treatment of spinal deformity with posterior spinal osteotomy. From January 2007 to December 2010, 321 cases of scoliosis or kyphosis patients were treated with posterior spinal osteotomy. There were 124 male and 197 female with an average age of (19 ± 11) years (2 - 56 years). The average preoperative main Cobb angle was 108° ± 33° (48° - 175°), the average kyphotic angle was 74° ± 29° (53° - 170°) before operation. Pedicle subtraction osteotomy was used in 226 cases, 95 cases with vertebral column resection. Pedicle screw-rod system was used for fixation. The patients were monitored by Somatosensory-evoked potentials monitoring and Stagnara wake-up test. There were 11 cases with varying degrees of new neurologic deficits and the total incidence was 3.4%. The causes were as followed, spinal translation in 2 cases, compromised by close of resected areas in 2 cases, residual bone compression in 1 case, inadvertent operation in 2 cases, screw malposition in 1 case, hematoma compression in 1 case and spine elongation in 2 cases. There was significant difference between the patients with preexisting neurologic deficits (20.0%) and the patients with intact neurologic function (2.6%) (χ(2) = 13.060, P = 0.011), no significant differences in different classes of the age, etiology, deformity, osteotomy type and surgical type (P > 0.05). But the incidence of neurologic deficits was 4.6% in congenital scoliosis, 7.1% in neuromuscular scoliosis, 5.1% in kyphosis, 5.9% in adult deformity and 5.9% in Cobb angle more than 100°, which was higher than other classes. All the 11 cases were given emergent Methylprednisolone, neurotrophic drugs and hyperbaric oxygen therapy, 4 cases were underwent surgical exploration again. After treatment, 7 cases recovered completely, 2 cases recovered partially and 2 cases failed to improve at the last follow-up. Severe spinal deformity could be effectively treated with posterior spinal osteotomy. But the procedure is technical demanding and risky for neurologic deficits. The high risk factor is preexisting neurologic deficits.

EphA Signaling Promotes Actin-based Dendritic Spine Remodeling through Slingshot Phosphatase

Actin cytoskeletal remodeling plays a critical role in transforming the morphology of subcellular structures across various cell types. In the brain, restructuring of dendritic spines through actin cytoskeleletal reorganization is implicated in the regulation of synaptic efficacy and the storage of information in neural circuits. However, the upstream pathways that provoke actin-based spine changes remain only partly understood. Here we show that EphA receptor signaling remodels spines by triggering a sequence of events involving actin filament rearrangement and synapse/spine reorganization. Rapid EphA signaling over minutes activates the actin filament depolymerizing/severing factor cofilin, alters F-actin distribution in spines, and causes transient spine elongation through the phosphatases slingshot 1 (SSH1) and calcineurin/protein phosphatase 2B (PP2B). This early phase of spine extension is followed by synaptic reorganization events that take place over minutes to hours and involve the relocation of pre/postsynaptic components and ultimately spine retraction. Thus, EphA receptors utilize discrete cellular and molecular pathways to promote actin-based structural plasticity of excitatory synapses.

Stimulation-Dependent Intraspinal Microtubules and Synaptic Failure in Alzheimer's Disease: A Review

There are many microtubules in axons and dendritic shafts, but it has been thought that there were fewer microtubules in spines. Recently, there have been four reports that observed the intraspinal microtubules. Because microtubules originate from the centrosome, these four reports strongly suggest a stimulation-dependent connection between the nucleus and the stimulated postsynaptic membrane by microtubules. In contrast, several pieces of evidence suggest that spine elongation may be caused by the polymerization of intraspinal microtubules. This structural mechanism for spine elongation suggests, conversely, that the synapse loss or spine loss observed in Alzheimer's disease may be caused by the depolymerization of intraspinal microtubules. Based on this evidence, it is suggested that the impairment of intraspinal microtubules may cause spinal structural change and block the translocation of plasticity-related molecules between the stimulated postsynaptic membranes and the nucleus, resulting in the cognitive deficits of Alzheimer's disease.

Influence of matrix metalloproteinase MMP-9 on dendritic spine morphology

An increasing body of data has shown that matrix metalloproteinase-9 (MMP-9), an extracellularly acting, Zn2+-dependent endopeptidase, is important not only for pathologies of the central nervous system but also for neuronal plasticity. Here, we use three independent experimental models to show that enzymatic activity of MMP-9 causes elongation and thinning of dendritic spines in the hippocampal neurons. These models are: a recently developed transgenic rat overexpressing autoactivating MMP-9, dissociated neuronal cultures, and organotypic neuronal cultures treated with recombinant autoactivating MMP-9. This dendritic effect is mediated by integrin β1 signalling. MMP-9 treatment also produces a change in the decay time of miniature synaptic currents; however, it does not change the abundance and localization of synaptic markers in dendritic protrusions. Our results, considered together with several recent studies, strongly imply that MMP-9 is functionally involved in synaptic remodelling.

Influence of matrix metalloproteinase MMP-9 on dendritic spine morphology

An increasing body of data has shown that matrix metalloproteinase-9 (MMP-9), an extracellularly acting, Zn(2+)-dependent endopeptidase, is important not only for pathologies of the central nervous system but also for neuronal plasticity. Here, we use three independent experimental models to show that enzymatic activity of MMP-9 causes elongation and thinning of dendritic spines in the hippocampal neurons. These models are: a recently developed transgenic rat overexpressing autoactivating MMP-9, dissociated neuronal cultures, and organotypic neuronal cultures treated with recombinant autoactivating MMP-9. This dendritic effect is mediated by integrin β1 signalling. MMP-9 treatment also produces a change in the decay time of miniature synaptic currents; however, it does not change the abundance and localization of synaptic markers in dendritic protrusions. Our results, considered together with several recent studies, strongly imply that MMP-9 is functionally involved in synaptic remodelling.

Early continuous inhibition of group 1 mGlu signaling partially rescues dendritic spine abnormalities in the Fmr1 knockout mouse model for fragile X syndrome

Abnormal dendritic spine morphology is a significant neuroanatomical defect in fragile X mental retardation. It has been suggested that overactive group 1 metabotropic glutamate receptor (mGlu) signaling is associated with the spine dysmorphology occurring in fragile X syndrome (FXS). Thus, group 1 mGlu became a new therapeutic target for the treatment of FXS. The purpose of this study was to identify the effect of inhibition of mGlu signaling in FXS. We observed the changes in dendritic spines after pharmacological modulation of mGlu signaling in an Fmr1 knockout (KO) mouse model. The activation of group 1 mGlu resulted in elongation of dendritic spines in the cultured neurons derived from Fmr1 KO mice and wild-type (WT) mice. Antagonism of group 1 mGlu reduced the average spine length of Fmr1 KO neurons. Furthermore, systemic administration of the selective group 1 mGlu5 antagonist 2-methyl-6-phenylethynyl pyridine (MPEP) reduced the average spine length and density in the cortical neurons of Fmr1 KO mice at developmental age. For the adult mice, MPEP administration was less effective for the restoration of spine length. The percentage of immature spines showed a similar reduction in parallel to the changes of spine length. Temporary MPEP intervention with single-dose treatment did not show any effect. These results show that MPEP administration could partially rescue the morphological deficits of dendritic spines in Fmr1 KO mice at developmental age.

Dynamic Network Connectivity: A new form of neuroplasticity

Prefrontal cortical (PFC) working memory functions depend on pyramidal cell networks that interconnect on dendritic spines. Recent research has revealed that the strength of PFC network connections can be rapidly and reversibly increased or decreased by molecular signaling events within slender, elongated spines: a process we term Dynamic Network Connectivity (DNC). This newly discovered form of neuroplasticity provides great flexibility in mental state, but also confers vulnerability and limits mental capacity. A remarkable number of genetic and/or environmental insults to DNC signaling cascades are associated with cognitive disorders such as schizophrenia and age-related cognitive decline. These insults can dysregulate network connections and erode higher cognitive abilities, leading to symptoms such as forgetfulness, susceptibility to interference, and disorganized thought and behavior.

THE NATURE OF FLARE RIBBONS IN CORONAL NULL-POINT TOPOLOGY

Flare ribbons are commonly attributed to the low-altitude impact, along the footprints of separatrices or quasi-separatrix layers (QSLs), of particle beams accelerated through magnetic reconnection. If reconnection occurs at a three-dimensional coronal magnetic null point, the footprint of the dome-shaped fan surface would map a closed circular ribbon. This paper addresses the following issues: does the entire circular ribbon brighten simultaneously, as expected because all fan field lines pass through the null point? And since the spine separatrices are singular field lines, do spine-related ribbons look like compact kernels? What can we learn from these observations about current sheet formation and magnetic reconnection in a null-point topology? The present study addresses these questions by analyzing Transition Region and Coronal Explorer and Solar and Heliospheric Observatory/Michelson Doppler Imager observations of a confined flare presenting a circular ribbon. Using a potential field extrapolation, we linked the circular shape of the ribbon with the photospheric mapping of the fan field lines originating from a coronal null point. Observations show that the flare ribbon outlining the fan lines brightens sequentially along the counterclockwise direction and that the spine-related ribbons are elongated. Using the potential field extrapolation as initial condition, we conduct a low-{beta} resistivemore » magnetohydrodynamics simulation of this observed event. We drive the coronal evolution by line-tied diverging boundary motions, so as to emulate the observed photospheric flow pattern associated with some magnetic flux emergence. The numerical analysis allows us to explain several observed features of the confined flare. The vorticity induced in the fan by the prescribed motions causes the spines to tear apart along the fan. This leads to formation of a thin current sheet and induces null-point reconnection. We also find that the null point and its associated topological structure is embedded within QSLs, already present in the asymmetric potential field configuration. We find that the QSL footprints correspond to the observed elongated spine ribbons. Finally, we observe that before and after reconnecting at the null point, all field lines undergo slipping and slip-running reconnection within the QSLs. Field lines, and therefore particle impacts, slip or slip-run according to their distance from the spine, in directions and over distances that are compatible with the observed dynamics of the ribbons.« less

Combinatorial morphogenesis of dendritic spines and filopodia by SPAR and α-actinin2

Rap small GTPases regulate excitatory synaptic strength and morphological plasticity of dendritic spines. Changes in spine structure are mediated by the F-actin cytoskeleton, but the link between Rap activity and actin dynamics is unclear. Here, we report a novel interaction between SPAR, a postsynaptic inhibitor of Rap, and α-actinin, a family of actin-cross-linking proteins. SPAR and α-actinin engage in bidirectional structural plasticity of dendritic spines: SPAR promotes spine head enlargement, whereas increased α-actinin2 expression favors dendritic spine elongation and thinning. Surprisingly, SPAR and α-actinin2 can function in an additive rather than antagonistic fashion at the same dendritic spine, generating combination spine/filopodia hybrids. These data identify a molecular pathway bridging the actin cytoskeleton and Rap at synapses, and suggest that formation of spines and filopodia are not necessarily opposing forms of structural plasticity.

A δ-Catenin Signaling Pathway Leading to Dendritic Protrusions

Delta-catenin is a synaptic adherens junction protein pivotally positioned to serve as a signaling sensor and integrator. Expression of delta-catenin induces filopodia-like protrusions in neurons. Here we show that the small GTPases of the Rho family act coordinately as downstream effectors of delta-catenin. A dominant negative Rac prevented delta-catenin-induced protrusions, and Cdc42 activity was dramatically increased by delta-catenin expression. A kinase dead LIMK (LIM kinase) and a mutant Cofilin also prevented delta-catenin-induced protrusions. To link the effects of delta-catenin to a physiological pathway, we noted that (S)-3,5-dihydroxyphenylglycine (DHPG) activation of metabotropic glutamate receptors induced dendritic protrusions that are very similar to those induced by delta-catenin. Furthermore, delta-catenin RNA-mediated interference can block the induction of dendritic protrusions by DHPG. Interestingly, DHPG dissociated PSD-95 and N-cadherin from the delta-catenin complex, increased the association of delta-catenin with Cortactin, and induced the phosphorylation of delta-catenin within the sites that bind to these protein partners.

Cessation of Reproduction‐Related Spine Elongation After Multiple Breeding Cycles in Female Naked Mole‐Rats

The breeding female or "queen" naked mole-rat has a uniquely elongated body morphology attributed to the lengthening of the lumbar vertebral column that occurs during pregnancy. It is unknown whether this vertebral growth is a continuous process, or associated only with early reproductive experience. We compared pregnancy-related bone elongation in nascent primiparous queens and established queens to determine if this vertebral expansion was a lifelong process in these females. We also investigated the impact of lactation on vertebral elongation in these mole-rats because it is known to be a time of significant bone loss in other mammals. Our data show that after eight or more pregnancies, established queens no longer experienced a net gain in lumbar spine length over the reproductive cycle, whereas the nascent breeders demonstrated significant spine lengthening over this time. Despite the lack of net spine lengthening in established breeders, our results indicated that these queens still experienced some pregnancy-specific vertebral elongation. In naked mole-rats, pregnancy-induced bone elongation may serve the dual purposes of first lengthening the spine, and then once optimal spine size is achieved, serving as a homeostatic mechanism that prepares the spine for the mineral demands of lactation. Anat Rec, 2009. (c) 2008 Wiley-Liss, Inc.

Modulation of dendritic spine remodeling in the motor cortex following spinal cord injury: Effects of environmental enrichment and combinatorial treatment with transplants and neurotrophin‐3

Incomplete spinal cord injury (SCI) elicits structural plasticity of the spared motor system, including the motor cortex, which may underlie some of the spontaneous recovery of motor function seen after injury. Promoting structural plasticity may become an important component of future strategies to improve functional outcomes. We have recently observed dynamic changes in the density and morphology of dendritic spines in the motor cortex following SCI. The present study sought to test whether SCI-induced changes in spine density and morphology could be modulated by potential strategies to enhance functional recovery. We examined the effects of enriched environment, transplants, and neurotrophin-3 on the plasticity of synaptic structures in the motor cortex following SCI. Housing rats in an enriched environment increased spine density in the motor cortex regardless of injury. SCI led to a more slender and elongated spine morphology. Enriched housing mitigated the SCI-induced morphological alterations, suggesting that the environmental modification facilitates maturation of synaptic structures. Transplantation of embryonic spinal cord tissue and delivery of neurotrophin-3 at the injury site further increased spine density when combined with enriched housing. This combinatorial treatment completely abolished the injury-induced changes, restoring a preinjury pattern of spine morphology. These results demonstrated that remodeling of dendritic spines in the motor cortex after SCI can be modulated by enriched housing, and the combinatorial treatment with embryonic transplants and neurotrophin-3 can potentiate the effects of enriched housing. We suggest that synaptic remodeling processes in the motor cortex can be targeted for an intervention to enhance functional recovery after SCI.