Disease relevance of Dendritic Spines

• A fragile X knockout (fmr1 KO) mouse has been described that has some of the characteristics of patients with fragile X syndrome, including immature dendritic spines and subtle behavioral deficits [1].
• We find a variety of effects on the density and morphology of dendritic spines by expressing either constitutively active or dominant negative forms of several small GTPases of the Rho family, by blocking the entire pathway with Clostridium difficile toxin B or by blocking Rho with C3 transferase [2].

Psychiatry related information on Dendritic Spines

• Defects in dendritic spines are common to several forms of cognitive deficits, including mental retardation and Alzheimer disease [3].
• These data suggest that long-lasting alterations in hippocampal dendritic spine density contribute to the neural mechanism underlying the olfactory bulbectomy model of depression, but not the neonatal clomipramine or maternal deprivation models [4].
• Acute total sleep deprivation for 48 h led to a significant decrease in noradrenaline, increase in the level of metabolites of monoamines, and an enhancement in the number of dendritic spines at the medial preoptic area (mPOA) [5].

High impact information on Dendritic Spines

• Here we report that the same signaling pathway in the postsynaptic CA1 pyramidal neuron also causes LTP of the slow inhibitory postsynaptic current (sIPSC) mediated by metabotropic GABA(B) receptors (GABA(B)-Rs) and G protein-activated inwardly rectifying K(+) (GIRK) channels, both residing in dendritic spines as well as shafts [6].
• Molecular manipulations of dynamin-like GTPases Drp1 and OPA1 that reduce dendritic mitochondria content lead to loss of synapses and dendritic spines, whereas increasing dendritic mitochondrial content or mitochondrial activity enhances the number and plasticity of spines and synapses [7].
• Here we describe the use of two-photon microscopy to image transient increases in Ca2+ concentration mediated by NMDA (N-methyl-D-aspartate) receptors in single dendritic spines of CA1 pyramidal neurons in hippocampal slices [8].
• Genetic knockout of NR3A in mice results in enhanced NMDA responses and increased dendritic spines in early postnatal cerebrocortical neurons [9].
• These differential effects of perturbing Rac1 activity indicate that there may be distinct mechanisms for the elaboration of axons, dendrites and dendritic spines [10].

Biological context of Dendritic Spines

• Thus, blocking SK channels facilitates the induction of long-term potentiation by enhancing NMDAR-dependent Ca(2+) signals within dendritic spines [11].
• We find that in mice, SK channels are localized to dendritic spines, and their activity reduces the amplitude of evoked synaptic potentials in an NMDA receptor (NMDAR)-dependent manner [11].
• Cyclic AMP controls BDNF-induced TrkB phosphorylation and dendritic spine formation in mature hippocampal neurons [12].
• Briefly preventing prostaglandin synthesis in newborn males with the COX inhibitor indomethacin permanently downregulates markers of dendritic spines in the POA and severely impairs male sexual behavior [13].
• The polarity protein PAR-3 and TIAM1 cooperate in dendritic spine morphogenesis [14].

Anatomical context of Dendritic Spines

• EphA4 is enriched on dendritic spines of pyramidal neurons in the adult mouse hippocampus, and ephrin-A3 is localized on astrocytic processes that envelop spines [15].
• These results reveal that the effect of glutamate on axonal filopodia is similar to its previously described effect on dendritic spines [16].
• Here we show that fear conditioning in rats leads to the movement of profilin, an actin polymerization-regulatory protein, into dendritic spines in the lateral amygdala and that these spines undergo enlargements in their postsynaptic densities (PSDs) [17].
• Synaptically evoked Ca(2+) transients were imaged in distal dendritic spines of pyramidal cells in cultured hippocampal slices, before and after the induction of LTP [18].
• Experience-dependent pruning of dendritic spines in visual cortex by tissue plasminogen activator [19].

Associations of Dendritic Spines with chemical compounds

• According to current models, the codistribution of two types of glutamate receptors in the postsynaptic membrane on dendritic spines is important for initiation of LTP [20].
• Raising the speed limit--fast Ca(2+) handling in dendritic spines [21].
• At the subcellular level, adenylate cyclases can be concentrated into dendritic spines, thereby increasing their susceptibility to multiple regulatory influences [22].
• We propose that the cadherin-beta-catenin complex is cotransported with AMPA receptors to synapses and dendritic spines by a mechanism that involves binding of liprin-alpha to LAR-RPTP and tyrosine dephosphorylation by LAR-RPTP [23].
• Learning and memory depend on dendritic spine actin assembly and docosahexaenoic acid (DHA), an essential n-3 (omega-3) polyunsaturated fatty acid (PFA) [24].

Gene context of Dendritic Spines

• In addition, cAMP facilitated trafficking of TrkB to dendritic spines, possibly by promoting its interaction with synaptic scaffolding protein PSD-95 [12].
• Furthermore, loss of a single copy of the Tsc1 gene was sufficient to perturb dendritic spine structure [25].
• EphB receptors regulate dendritic spine development via intersectin, Cdc42 and N-WASP [26].
• Neurabin and spinophilin are homologous protein phosphatase 1 and actin binding proteins that regulate dendritic spine function [27].
• Loss of potentiation was correlated with faster turnover of monomeric SAP97 mutants in dendritic spines [28].

Analytical, diagnostic and therapeutic context of Dendritic Spines

• We have examined this issue in layer V cortical pyramidal neurons, using focal flash photolysis of caged glutamate to mimic synaptic input and two-photon, laser-scanning microscopy to measure calcium levels in dendritic spines [29].
• Electron microscopy combined with GABA postimmunogold labeling revealed that most (>90%) of the synaptic contacts were established on dendritic spines and shafts of excitatory neurons in layers 4 and 2/3 [30].
• Removal of circulating gonadal steroids by ovariectomy of adult female rats resulted in a profound decrease in dendritic spine density in CA1 pyramidal cells of the hippocampus [31].
• Molecular cloning and characterization of phocein, a protein found from the Golgi complex to dendritic spines [32].
• Studies of neurons from human epilepsy tissue and comparable animal models of focal epilepsy have consistently reported a marked decrease in dendritic spine density on hippocampal and neocortical pyramidal cells [33].

References