Spine-Neck Geometry Determines NMDA Receptor-Dependent Ca2+ Signaling in Dendrites

Noguchi, Junjirō; Matsuzaki, Masunori; Ellis‐Davies, Graham C. R.; Kasai, Hideaki

doi:10.1016/j.neuron.2005.03.015

Cited by 375 publications

(397 citation statements)

References 57 publications

(97 reference statements)

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“…This appears contrary to studies describing a linear correlation between spine volume and synaptic strength (29,30), work performed in rat CA1 pyramidal neurons or rat olfactory cortex cultured cells. We cannot rule out that morphological analysis of the data with better spatial resolution could reveal such a correlation, once the neck effect is taken into account.…”

Section: Discussioncontrasting

confidence: 92%

The spine neck filters membrane potentials

Araya

Jiang

Eisenthal

et al. 2006

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

234

268

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Dendritic spines receive most synaptic inputs in the forebrain. Their morphology, with a spine head isolated from the dendrite by a slender neck, indicates a potential role in isolating inputs. Indeed, biochemical compartmentalization occurs at spine heads because of the diffusional bottleneck created by the spine neck. Here we investigate whether the spine neck also isolates inputs electrically. Using two-photon uncaging of glutamate on spine heads from mouse layer-5 neocortical pyramidal cells, we find that the amplitude of uncaging potentials at the soma is inversely proportional to neck length. This effect is strong and independent of the position of the spine in the dendritic tree and size of the spine head. Moreover, spines with long necks are electrically silent at the soma, although their heads are activated by the uncaging event, as determined with calcium imaging. Finally, second harmonic measurements of membrane potential reveal an attenuation of somatic voltages into the spine head, an attenuation directly proportional to neck length. We conclude that the spine neck plays an electrical role in the transmission of membrane potentials, isolating synapses electrically.second harmonic ͉ electrical isolation ͉ uncaging ͉ cortex ͉ glutamate T he dendritic spine is a ubiquitous feature in the nervous system, whose function is still poorly understood and heavily investigated (1). Spines are recipients of excitatory inputs in many neurons, including pyramidal cells (2), but excitatory inputs in nonspiny neurons contact dendritic shafts. Therefore, rather than just serving as recipients of inputs, spines likely perform a specific function with those inputs. Indeed, spines are calcium compartments and can therefore restrict local biochemical reactions to single inputs (3, 4). Nevertheless, nonspiny neurons can also perform similar calcium compartmentalization (5, 6), so it is conceivable that spines could implement an additional function.Theoretical work, spanning several decades, has proposed that spines could play an important role in altering synaptic potentials (7-12) (for a recent review, see ref. 13). Because of the resistance of the spine neck, spines could electrically isolate inputs and thus prevent input resistance variations in the dendrite during synaptic transmission (8). Thus, excitatory synaptic potentials could be filtered when they reach the dendrite (8-10, 12).The resistance of the spine neck, a crucial variable in ascertaining the electrical function of the spine, has never been measured. Estimates made from passive cable models (14) or diffusional coupling (15) would make its value too low to significantly filter synaptic potentials. At the same time, recent diffusional estimates indicate that neck resistances could be higher (16). Indeed, in our recent work examining input integration, we found that potentials onto spines sum linearly, whereas depolarizations on dendritic shafts shunt each other (R.A., K.B.E., and R.Y., unpublished work). Thus, our data would imply that spines isolate input...

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Section: Discussioncontrasting

confidence: 92%

The spine neck filters membrane potentials

Araya

Jiang

Eisenthal

et al. 2006

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

234

268

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“…Regarding their individual geometrical dimensions, recent studies have proposed that spine length in hippocampal pyramidal neurons contributes to spine-dendrite coupling of Ca 2+ signals Korkotian et al, 2004;Majewska et al, 2000). Furthermore, the dimensions and geometry of the spine neck in CA1 pyramidal neurons have been shown to determine NMDARdependent Ca 2+ signaling in the parent dendrite (Noguchi et al, 2005). We interpret that the BDNF-induced structural remodeling of spiny dendrites has consequences for Ca 2+ signals evoked by coincident pre-and postsynaptic activity.…”

Section: Discussionmentioning

confidence: 61%

“…These larger spines with wider necks are thought to represent spines that acquired AMPA receptors immediately after the induction of long-term potentiation (Matsuzaki et al, 2001;Kasai et al, 2003), and thus enhance spine-dendrite coupling leading to widespread dendritic Ca 2+ signaling during excitatory synaptic transmission (Noguchi et al, 2005). Together with the morphological effects of BDNF on presynaptic terminals (Tyler et al, 2002b) and postsynaptic spine growth and form Pozzo-Miller, 2001, 2003;Alonso et al, 2004), we propose that the larger Ca 2+ signals in spiny dendrites during coincident pre-and postsynaptic activation represent a physiological consequence of the structural BDNF actions at hippocampal synapses.…”

Section: Discussionmentioning

confidence: 99%

BDNF enhances dendritic Ca2+ signals evoked by coincident EPSPs and back-propagating action potentials in CA1 pyramidal neurons

Pozzo-Miller

2006

Brain Research

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BDNF, a member of the neurotrophin family, is emerging as a key modulator of synaptic structure and function in the CNS. Due to the critical role of postsynaptic Ca 2+ signals in dendritic development and synaptic plasticity, we tested whether long-term exposure to BDNF affects Ca 2+ elevations evoked by coincident excitatory postsynaptic potentials (EPSPs) and back-propagating action potentials (bAPs) in spiny dendrites of CA1 pyramidal neurons within hippocampal slice cultures. In control neurons, a train of 5 coincident EPSPs and bAPs evoked Ca 2+ elevations in oblique radial branches of the main apical dendrite that were of similar amplitude than those evoked by a train of 5 bAPs alone. On the other hand, dendritic Ca 2+ signals evoked by coincident EPSPs and bAPs were always larger than those triggered by bAPs in CA1 neurons exposed to BDNF for 48 h. This difference was not observed after blockade of NMDA receptors (NMDARs) with D,L-APV, but only in BDNFtreated neurons, suggesting that Ca 2+ signals in oblique radial dendrites include a synaptic NMDARdependent component. Co-treatment with the receptor tyrosine kinase inhibitor k-252a prevented the effect of BDNF on coincident dendritic Ca 2+ signals, suggesting the involvement of neurotrophin Trk receptors. These results indicate that long-term exposure to BDNF enhances Ca 2+ signaling during coincident pre-and postsynaptic activity in small spiny dendrites of CA1 pyramidal neurons, representing a potential functional consequence of neurotrophin-mediated dendritic remodeling in developing neurons.

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“…Consistent with these observations, the equilibrium of F-actin is also is bidirectionally regulated by the frequency of synaptic activity (Okamoto, et al, 2004). While the relationship between homeostatic enhancements in synaptic NMDA receptor clustering and dendritic spines has not been previously investigated, the number of NMDA receptors in a spine is proportional to its size (Noguchi, et al, 2005). Thus, events that promote greater synaptic clustering of NMDA receptors could impact spine number and morphology through NMDA receptor-dependent mechanisms.…”

Section: Dendritic Spines and Learningmentioning

confidence: 71%

Adaptive plasticity of NMDA receptors and dendritic spines: Implications for enhanced vulnerability of the adolescent brain to alcohol addiction

Carpenter-Hyland

Chandler

2007

Pharmacology Biochemistry and Behavior

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It is now known that brain development continues into adolescence and early adulthood and is highly influenced by experience-dependent adaptive plasticity during this time. Behaviorally, this period is also characterized by increased novelty-seeking and risk-taking. This heightened plasticity appears to be important in shaping behaviors and cognitive processes that contribute to proper development of an adult phenotype. However, increasing evidence has linked these same experience-dependent learning mechanisms with processes that underlie drug addiction. As such, the adolescent brain appears be particularly susceptible to experience-dependent learning processes associated with consumption of alcohol and addictive drugs. At the level of the synapse, homeostatic changes during ethanol consumption are invoked to counter the destabilizing effects of ethanol on neural networks. This homeostatic response may be especially pronounced in the adolescent and young adult brain due to its heightened capacity to undergo experience-dependent changes, and appears to involve increased synaptic targeting of NMDA receptors. Interestingly, recent work from our lab also indicates that the enhanced synaptic localization of NMDA receptors promotes increases in the size of dendritic spines. This increase may represent a structural-based mechanism that supports the formation and stabilization of maladapted synaptic connections that, in a sense, "fix" the addictive behavior in the adolescent and young adult brain.

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Spine-Neck Geometry Determines NMDA Receptor-Dependent Ca2+ Signaling in Dendrites

Cited by 375 publications

References 57 publications

The spine neck filters membrane potentials

The spine neck filters membrane potentials

BDNF enhances dendritic Ca2+ signals evoked by coincident EPSPs and back-propagating action potentials in CA1 pyramidal neurons

Adaptive plasticity of NMDA receptors and dendritic spines: Implications for enhanced vulnerability of the adolescent brain to alcohol addiction

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