Biomedical subjects

Anna Dunaevsky

Publications and source records attributed to Anna Dunaevsky.

8 recordsLinked to original sources

PubMed2006

Amyloid beta peptide adversely affects spine number and motility in hippocampal neurons.

Elevated levels of amyloid-beta peptide (Abeta) are found in Down's syndrome patients and alter synaptic function during the early stages of Alzheimer's disease. Dendritic spines, sites of most excitatory synaptic contacts, are considered to be an important locus for encoding synaptic plasticity. We used time-lapse two-photon imaging of hippocampal pyramidal neurons in organotypic slices to study the effects of Abeta on the development of dendritic spines. We report that exposure of hippocampal neurons to sub-lethal levels of Abeta decreased spine density, increased spine length and subdued spine motility. The effect of Abeta on spine density was reversible. Moreover, Abeta's effect on dendritic spine density was blocked by rolipram, a phosphodiesterase type IV inhibitor, suggesting the involvement of a cAMP dependent pathway. These findings raise the possibility that Abeta-induced spine alterations could underlie the cognitive defects in Alzheimer's disease and Down syndrome.

Amyloid beta-Peptides↗

PubMed2006

Dendritic spine plasticity: looking beyond development.

Most excitatory synapses in the CNS form on dendritic spines, tiny protrusions from the dendrites of excitatory neurons. As such, spines are likely loci of synaptic plasticity. Spines are dynamic structures, but the functional consequences of dynamic changes in these structures in the mature brain are unclear. Changes in spine density, morphology, and motility have been shown to occur with paradigms that induce synaptic plasticity, as well as altered sensory experience and neuronal activity. These changes potentially lead to an alteration in synaptic connectivity and strength between neuronal partners, affecting the efficacy of synaptic communication. Here, we review the formation and modification of excitatory synapses on dendritic spines as it relates to plasticity in the central nervous system after the initial phase of synaptogenesis. We will also discuss some of the molecular links that have been implicated in both synaptic plasticity and the regulation of spine morphology.

Animals↗

PubMed2005

Purkinje cell dendrites grow in alignment with Bergmann glia.

The pattern of growth of Purkinje cell dendrites has been analyzed and related to their interactions with Bergmann glial radial processes. In cerebellar slice cultures from mice expressing green fluorescent protein (GFP) under the glial fibrillary acidic protein (GFAP) promoter, Purkinje cells were transfected and imaged with two-photon microscopy over 2 days. We report that while the Purkinje cell dendritic tree grows, individual dendrites increase or decrease in length. Importantly, we demonstrate that vertical growth of Purkinje cell dendrites occurs primarily in alignment with radial glial processes. These findings suggest that radial glial processes provide a structural substrate for the directional growth of Purkinje cell dendrites, thus influencing the shape of the dendritic tree.

Animals↗

PubMed2005

Dynamics of dendritic spines and their afferent terminals: spines are more motile than presynaptic boutons.

Previous work has established that dendritic spines, sites of excitatory input in CNS neurons, can be highly dynamic, in later development as well as in mature brain. Although spine motility has been proposed to facilitate the formation of new synaptic contacts, we have reported that spines continue to be dynamic even if they bear synaptic contacts. An outstanding question related to this finding is whether the presynaptic terminals that contact dendritic spines are as dynamic as their postsynaptic targets. Using multiphoton time-lapse microscopy of GFP-labeled Purkinje cells and DiI-labeled granule cell parallel fiber afferents in cerebellar slices, we monitored the dynamic behavior of both presynaptic terminals and postsynaptic dendritic spines in the same preparation. We report that while spines are dynamic, the presynaptic terminals they contact are quite stable. We confirmed the relatively low levels of presynaptic terminal motility by imaging parallel fibers in vivo. Finally, spine motility can occur when a functional presynaptic terminal is apposed to it. These analyses further call into question the function of spine motility, and to what extent the synapse breaks or maintains its contact during the movement of the spine.

Animals↗

PubMed2005

Dendritic spine morphogenesis and plasticity.

Dendritic spines are small protrusions off the dendrite that receive excitatory synaptic input. Spines vary in size, likely correlating with the strength of the synapses they form. In the developing brain, spines show highly dynamic behavior thought to facilitate the formation of new synaptic contacts. Recent studies have illuminated the numerous molecules regulating spine development, many of which converge on the regulation of actin filaments. In addition, interactions with glial cells are emerging as important regulators of spine morphology. In many cases, spine morphogenesis, plasticity, and maintenance also depend on synaptic activity, as shown by recent studies demonstrating changes in spine dynamics and maintenance with altered sensory experience.

Animals↗

PubMed2004

Connecting the dots: from actin polymerization to synapse formation.

Protrusive behavior of dendritic spines on developing neurons has been previously suggested to mediate the formation of new axodendritic synaptic contacts. A study by Zito et al. in this issue of Neuron links actin polymerization in dendritic spines with the motility that the spines exhibit and the synapses that they form.

Actins↗

PubMed2003

Bidirectional regulation of hippocampal mossy fiber filopodial motility by kainate receptors: a two-step model of synaptogenesis.

The rapid motility of axonal filopodia and dendritic spines is prevalent throughout the developing CNS, although the function of this motility remains controversial. Using two-photon microscopy, we imaged hippocampal mossy fiber axons in slice cultures and discovered that filopodial extensions are highly motile. Axonal filopodial motility is actin based and is downregulated with development, although it remains in mature cultures. This motility is correlated with free extracellular space yet is inversely correlated with contact with postsynaptic targets, indicating a potential role in synaptogenesis. Filopodial motility is differentially regulated by kainate receptors: synaptic stimulation of kainate receptors enhances motility in younger slices, but it inhibits it in mature slices. We propose that neuronal activity controls filopodial motility in a developmentally regulated manner, in order to establish synaptic contacts in a two-step process. A two-step model of synaptogenesis can also explain the opposite effects of neuronal activity on the motility of dendritic protrusions.

Actin Cytoskeleton↗

PubMed2003

Spine motility: a means towards an end?

From the first glimpse of moving spines half a decade ago, the prevailing view has been that spine contortions and wiggling, especially during development, maximize encounters with presynaptic growth cones or synaptic boutons. Other new evidence has revealed that spines continue to be motile even after they settle on a presynaptic partner and form a synapse. We present the evidence for each view, and discuss how spines with synapses could move relative to their apparently stable presynaptic partners. Thus, spine motility might not simply be a means towards an end of synapse formation, but could continue, albeit at a lower rate, during synapse turnover after development ends.

Animals↗