Synaptopodin-deficient mice lack a spine apparatus and show deficits in synaptic plasticity

Deller, Thomas; Körte, Martin; Chabanis, Sophie; Drakew, Alexander; Schwegler, Herbert; Stefani, Giulia Good; Zúñiga, Aimée; Schwarz, Karin; Bonhoeffer, Tobias; Zeller, Rolf; Frotscher, Michael; Mündel, Peter

doi:10.1073/pnas.1832384100

Cited by 264 publications

(368 citation statements)

References 38 publications

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“…An analysis of the spine-head diameters of the same spines yielded a median value of 380 nm and a range of spine-head diameters from 70 (this value is actually the thickest diameter of the smallest dendritic filopodium) to 710 nm. These values are in good agreement with the dimensions known from serialsection electron microscopy and other super-resolution images in the literature [22][23][24][25][26] .…”

Section: Images From Biological Structuressupporting

confidence: 90%

Fluorescence nanoscopy by polarization modulation and polarization angle narrowing

et al. 2014

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When excited with rotating linear polarized light, differently oriented fluorescent dyes emit periodic signals peaking at different times. We show that measurement of the average orientation of fluorescent dyes attached to rigid sample structures mapped to regularly defined (50 nm) 2 image nanoareas can provide subdiffraction resolution (super resolution by polarization demodulation, sPod). Because the polarization angle range for effective excitation of an oriented molecule is rather broad and unspecific, we narrowed this range by simultaneous irradiation with a second, de-excitation, beam possessing a polarization perpendicular to the excitation beam (excitation polarization angle narrowing, exPAn). this shortened the periodic emission flashes, allowing better discrimination between molecules or nanoareas. our method requires neither the generation of nanometric interference structures nor the use of switchable or blinking fluorescent probes. We applied the method to standard wide-field microscopy with camera detection and to two-photon scanning microscopy, imaging the fine structural details of neuronal spines.In recent years the development of super-resolution techniques has had a profound impact on biology and other fields in which subdiffraction-limited resolution of fluorescently labeled samples is desired [1][2][3][4][5][6][7][8][9][10][11][12][13] . Prominent examples are stimulated emission depletion (STED) microscopy 1,4 , photoactivated localization microscopy (PALM) 3,5,6 and stochastic optical reconstruction microscopy (STORM) 2,7 . Generally, these techniques are based on reversible switching between two states. Whereas STED is based on a deterministic switching in a nanometric interference pattern, STORM and PALM are based on wide-field illumination and stochastic switching on the level of single isolated molecules, which are then localized. Other approaches, such as super-resolution optical fluctuation imaging (SOFI) 8 , reversible saturable optical fluorescence transitions (RESOLFT) microscopy 9,11 and saturated structured illumination microscopy (SSIM) 12,13 , are also based on stochastic or deterministic switching between two states and provide spatial resolution enhancement. Here we present an alternative approach that distinguishes adjacent molecules or nanoareas in the sample (arranged, for example, in a grid of 50 nm × 50 nm rectangular areas) by different average orientations of fluorescent dyes attached to rigid sample structures within these nanoareas. This is done by rotating the polarization of a wide-field excitation beam and detecting the periodic signals emitted with different phases from different nanoareas using wide-field camera detection (SPoD). We also show that the range of polarization angles that results in effective excitation of differently oriented molecules can be substantially narrowed by rotating a second wide-field de-exciting stimulated emission beam of a polarization perpendicular to the excitation beam polarization (ExPAN), resulting in better spatial resolution ...

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Section: Images From Biological Structuressupporting

confidence: 90%

Fluorescence nanoscopy by polarization modulation and polarization angle narrowing

et al. 2014

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“…Strikingly, most of these transcripts were expressed at a higher level in the VTA neurons. The factors with a reported or anticipated function in synaptic plasticity included the synaptic-adhesion molecules synCAM and syndecan 2 (29) and the actin-associated synaptopodin 2, which is required for the formation of the dendriticspine apparatus (30). The MARCKS and G substrate have been implicated in learning and long-term potentiation.…”

Section: Resultsmentioning

confidence: 99%

Molecular basis for catecholaminergic neuron diversity

Grimm

Mueller

Hefti

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

131

141

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Catecholaminergic neurons control diverse cognitive, motor, and endocrine functions and are associated with multiple psychiatric and neurodegenerative disorders. We present global gene-expression profiles that define the four major classes of dopaminergic (DA) and noradrenergic neurons in the brain. Hypothalamic DA neurons and noradrenergic neurons in the locus coeruleus display distinct group-specific signatures of transporters, channels, transcription, plasticity, axon-guidance, and survival factors. In contrast, the transcriptomes of midbrain DA neurons of the substantia nigra and the ventral tegmental area are closely related with <1% of differentially expressed genes. Transcripts implicated in neural plasticity and survival are enriched in ventral tegmental area neurons, consistent with their role in schizophrenia and addiction and their decreased vulnerability in Parkinson's disease. The molecular profiles presented provide a basis for understanding the common and population-specific properties of catecholaminergic neurons and will facilitate the development of selective drugs.C atecholaminergic (CA) neurons producing the neurotransmitters dopamine (DA) and noradrenalin (NA) are organized in anatomically discrete groups and constitute Ϸ1 of 10 7 cells in the vertebrate CNS (1, 2). The most prominent groups of DA neurons reside in the substantia nigra (SN; A9 cell group; Ϸ10,000 neurons in the rat) and the ventral tegmental area (VTA; A10; Ϸ25,000 neurons) of the midbrain. The SN neurons provide the nigrostriatal ascending inputs to the telencephalon and comprise a key component of the extrapyramidal motor system controlling postural reflexes and initiation of movement. DA neurons in the adjacent VTA give rise to mesocortical and mesolimbic pathways that are implicated in control of emotional balance, reward-associated behavior, attention, and memory. Additional groups of DA neurons reside in the medial zona incerta of the hypothalamus (A13; Ϸ900 neurons) and participate in the regulation of endocrine functions. The largest collection of NA neurons resides in the pontine locus coeruleus (LC; Ϸ1,500 neurons). These neurons form a modulatory projection system to most CNS areas and contribute to the regulation of emotional status, sensory perception, arousal, sleepwake patterns, and most autonomic functions.Consistent with their varied functions, the CA neurons are associated with multiple neurodegenerative, psychiatric, and endocrine disorders. Selective degeneration of DA neurons in the SN but not in the VTA or the hypothalamus leads to Parkinson's disease (PD) (3-7), whereas abnormal function of the VTA DA neurons has been linked to schizophrenia, attention deficit, addiction, and hyperactivity disorders (8-11). In addition, dysfunction of hypothalamic DA neurons can cause hyperprolactinemia, an endocrine disorder of the reproductive system (12), whereas changes in the activity of the NA system have been linked to depression as well as sleep disorders (13,14).The drugs currently available for therapy reflec...

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“…Moreover, we identified two brain-enriched proteins important for synaptic function, synaptopodin and bassoon. The actin-associated protein synaptopodin is essential for dendritic spine formation, with synaptopodin-deficient mice exhibiting a lack of spine apparatuses and impaired long-term potentiation and spatial learning (45). Bassoon, a scaffolding protein of the cytomatrix assembled at the active zone, plays a critical role in synaptic vesicle cycling (46).…”

Section: Discussionmentioning

confidence: 99%

Exploring the O -GlcNAc proteome: Direct identification of O -GlcNAc-modified proteins from the brain

Khidekel

Ficarro²,

Peters³

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

279

250

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Synaptopodin-deficient mice lack a spine apparatus and show deficits in synaptic plasticity

Cited by 264 publications

References 38 publications

Fluorescence nanoscopy by polarization modulation and polarization angle narrowing

Fluorescence nanoscopy by polarization modulation and polarization angle narrowing

Molecular basis for catecholaminergic neuron diversity

Exploring the O -GlcNAc proteome: Direct identification of O -GlcNAc-modified proteins from the brain

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