Optogenetic Control of Spine-Head JNK Reveals a Role in Dendritic Spine Regression

1. Because induction of associative long-term potentiation (LTP) in the dentate gyrus is thought to depend on Ca2+ influx through channels controlled by N-methyl-D-aspartate (NMDA) receptors, quantitative modeling was performed of synaptically mediated Ca2+ influx as a function of synaptic coactivation. The goal was to determine whether Ca2+ influx through NMDA-receptor channels was, by itself, sufficient to explain associative LTP, including control experiments and the temporal requirements of LTP. 2. Ca2+ influx through NMDA-receptor channels was modeled at a synapse on a dendritic spine of a reconstructed hippocampal dentate granule cell when 1-115 synapses on spines at different dendritic locations were activated eight times at frequencies of 10-800 Hz. The resulting change in [Ca2+] in the spine head was estimated from the Ca2+ influx with the use of a model of a dendritic spine that included Ca2+ buffers, pumps, and diffusion. 3. To use a compelling model of synaptic activation, we developed quantitative descriptions of the NMDA and non-NMDA receptor-mediated conductances consistent with available experimental data. The experimental data reported for NMDA and non-NMDA receptor-channel properties and data from other non-LTP experiments that separated the NMDA and non-NMDA receptor-mediated components of synaptic events proved to be limiting for particular synaptic variables. Relative to the non-NMDA glutamate-type receptors, 1) the unbinding of transmitter from NMDA receptors had to be slow, 2) the transition from the bound NMDA receptor-transmitter complex to the open channel state had to be even slower, and 3) the average number of NMDA-receptor channels at a single activated synapse on a single spine head that were open and conducting at a given moment in time had to be very small (usually less than 1). 4. With the use of these quantitative synaptic conductance descriptions. Ca2+ influx through NMDA-receptor channels at a synapse was computed for a variety of conditions. For a constant number of pulses, Ca2+ influx was calculated as a function of input frequency and the number of coactivated synapses. When few synapses were coactivated, Ca2+ influx was small, even for high-frequency activation. However, with larger numbers of coactivated synapses, there was a steep increase in Ca2+ influx with increasing input frequency because of the voltage-dependent nature of the NMDA receptor-mediated conductance. Nevertheless, total Ca2+ influx was never increased more than fourfold by increasing input frequency or the number of coactivated synapses.(ABSTRACT TRUNCATED AT 400 WORDS)

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Glial glutamate transport modulates dendritic spine head protrusions in the hippocampus

Glia ◽

10.1002/glia.22335 ◽

2012 ◽

Vol 60 (7) ◽

pp. 1067-1077 ◽

Cited By ~ 30

Author(s):

David Verbich ◽

George A. Prenosil ◽

Philip K.-Y. Chang ◽

Keith K. Murai ◽

R. Anne McKinney

Keyword(s):

Dendritic Spine ◽

Glutamate Transport ◽

Spine Head

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The Actin-Binding Protein Abp1 Controls Dendritic Spine Morphology and Is Important for Spine Head and Synapse Formation

Journal of Neuroscience ◽

10.1523/jneurosci.0336-08.2008 ◽

2008 ◽

Vol 28 (40) ◽

pp. 10031-10044 ◽

Cited By ~ 59

Author(s):

A. Haeckel ◽

R. Ahuja ◽

E. D. Gundelfinger ◽

B. Qualmann ◽

M. M. Kessels

Keyword(s):

Dendritic Spine ◽

Synapse Formation ◽

Binding Protein ◽

Actin Binding ◽

Spine Morphology ◽

Actin Binding Protein ◽

Spine Head ◽

Dendritic Spine Morphology

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Sevoflurane Causes Long‐lasting Dendritic Spine Head Enlargement without Lasting Effect on Neuritic Extension

The FASEB Journal ◽

10.1096/fasebj.29.1_supplement.lb43 ◽

2015 ◽

Vol 29 (S1) ◽

Author(s):

J Zimering ◽

Y Dong ◽

F Fang ◽

Y Zhang ◽

Z Xie

Keyword(s):

Dendritic Spine ◽

Spine Head ◽

Lasting Effect

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Automated quantification of dendritic spine density and spine head diameter in medium spiny neurons of the nucleus accumbens

Brain Structure and Function ◽

10.1007/s00429-008-0184-2 ◽

2008 ◽

Vol 213 (1-2) ◽

pp. 149-157 ◽

Cited By ~ 49

Author(s):

Haowei Shen ◽

Susan R. Sesack ◽

Shigenobu Toda ◽

Peter W. Kalivas

Keyword(s):

Nucleus Accumbens ◽

Dendritic Spine ◽

Medium Spiny Neurons ◽

Spine Density ◽

Head Diameter ◽

Spine Head ◽

Spiny Neurons ◽

Dendritic Spine Density ◽

Automated Quantification

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Heroin self-administration and extinction increases prelimbic cortical astroglia-synapse proximity and alters dendritic spine morphometrics that are reversed by N-acetylcysteine

10.1101/2020.05.21.108530 ◽

2020 ◽

Author(s):

BM Siemsen ◽

KN Hooker ◽

EA Carpenter ◽

ME Prescott ◽

AG Brock ◽

...

Keyword(s):

Ampa Receptors ◽

Dendritic Spine ◽

Pyramidal Neurons ◽

Glutamate Release ◽

Repeated Treatment ◽

Spine Density ◽

Sprague Dawley ◽

Self Administration ◽

Spine Head ◽

Synaptic Markers

AbstractClinical and preclinical studies indicate that adaptations in corticostriatal neurotransmission significantly contribute to heroin relapse vulnerability. In animal models, heroin self-administration and extinction produce cellular adaptations in both neurons and astrocytes within the nucleus accumbens (NA) core that are required for cue-induced heroin seeking. Specifically, decreased glutamate clearance and reduced association of perisynaptic astrocytic processes with NAcore synapses allow glutamate release from prelimbic (PrL) cortical terminals to engage synaptic and structural plasticity in NAcore medium spiny neurons. Normalizing astroglial glutamate homeostasis with drugs like the antioxidant N-acetylcysteine (NAC) prevents cue-induced heroin seeking. Surprisingly, little is known about heroin-induced alterations in astrocytes or pyramidal neurons projecting to the NAcore in the PrL cortex (PrL-NAcore). Here, we observed increased complexity of the glial fibrillary acidic protein (GFAP) cytoskeletal arbor and increased association of the astroglial plasma membrane with synaptic markers following heroin SA and extinction training in the PrL cortex. Repeated treatment with NAC during extinction reversed both the enhanced astroglial complexity and synaptic association. In PrL-NAcore neurons, heroin SA and extinction decreased apical tuft dendritic spine density and enlarged dendritic spine head diameter in male Sprague-Dawley rats. Repeated NAC treatment during extinction prevented decreases in spine density but not dendritic spine head expansion. Moreover, heroin SA and extinction increased co-registry of the GluA1 subunit of AMPA receptors in both the dendrite shaft and spine heads of PrL-NAcore neurons. Interestingly, accumulation of GluA1 immunoreactivity in spine heads was further potentiated by NAC treatment during extinction. Taken together, our data reveal circuit-level adaptations in cortical dendritic spine morphology potentially linked to heroin-induced alterations in astrocyte complexity and association at synapses. Additionally, these data demonstrate, for the first time, that NAC reverses PrL cortical heroin SA and extinction-induced adaptations in both astrocytes and corticostriatal neurons.

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Computational study of an excitable dendritic spine

Journal of Neurophysiology ◽

10.1152/jn.1988.60.2.499 ◽

1988 ◽

Vol 60 (2) ◽

pp. 499-523 ◽

Cited By ~ 132

Author(s):

I. Segev ◽

W. Rall

Keyword(s):

Action Potential ◽

Threshold Voltage ◽

Dendritic Spine ◽

Excitable Membrane ◽

Membrane Properties ◽

Equilibrium Potential ◽

Optimal Range ◽

Epsp Amplitude ◽

Spike Threshold ◽

Spine Head

1. A compartmental model was employed to investigate the electrical behavior of a dendritic spine having excitable membrane at the spine head. Here we used the Hodgkin and Huxley equations to generate excitable membrane properties; in some cases the kinetics were modified to get a longer duration action potential. Passive membrane was assumed for both the spine stem and the dendritic shaft. Synaptic input was modeled as a transient conductance increase (alpha-function) that lies in series with a battery (that corresponds to an excitatory or inhibitory synaptic equilibrium potential). 2. Threshold conditions for an action potential at the spine head membrane were found to be sensitive to the membrane properties at the spine head and to the conductance loading provided by the spine stem and the dendritic tree. Increasing either the number or the open times of the excitable channels had the effect of lowering spike threshold voltage. Increasing the spine stem resistance (RSS) or increasing the input resistance at the spinal base (RSB) also lowered the spike threshold voltage. Because a preexisting dendritic depolarization reduced the spine stem current, this lowered the spike threshold voltage, and this threshold was also shown to be sensitive to the distribution of membrane potential along the dendrite. 3. For each set of spine and dendritic parameters, there was an optimal range of RSS values for which the excitable properties at the spine head membrane resulted in maximal amplification of the dendritic excitatory postsynaptic potential (EPSP), when compared with that produced by a corresponding passive spine. This optimal range depended (with nonlinear sensitivity) on the properties of the voltage-gated channels at the spine head membrane. The maximal amplification found (for each of several sets of parameters) ranged from two to thirteen times. 4. Near this optimal range of RSS values, there was maximal (nonlinear) sensitivity of the dendritic EPSP amplitude to small changes in RSS. A minor decrease resulted in a subthreshold response at the spine head, and this resulted in a large decrease in the EPSP amplitude at the spine base. Increasing the value of RSS above this optimal range decreased the amount of spine stem current flowing to the spine base (by Ohm's law); this decreased the EPSP amplitude at the spine base. The demonstration of this optimum agrees with earlier expectations and results. 5. Excitable dendritic spines can be seen to provide an anatomical arrangement that economizes both excitable and synaptic channels. A small number of these channels (located in spine head membrane) can produce a large dendritic depolarization.(ABSTRACT TRUNCATED AT 400 WORDS)

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Geometry of Dendritic Spines Affects Calcium Dynamics in Hippocampal Neurons: Theory and Experiments

Journal of Neurophysiology ◽

10.1152/jn.1999.82.1.450 ◽

1999 ◽

Vol 82 (1) ◽

pp. 450-462 ◽

Cited By ~ 59

Author(s):

N. Volfovsky ◽

H. Parnas ◽

M. Segal ◽

E. Korkotian

Keyword(s):

Dendritic Spines ◽

Dendritic Spine ◽

Hippocampal Neurons ◽

Laser Scanning ◽

Nonlinear Differential Equations ◽

Confocal Laser ◽

Calcium Dynamics ◽

Spine Head ◽

The Impact ◽

Cultured Hippocampal Neurons

The role of dendritic spine morphology in the regulation of the spatiotemporal distribution of free intracellular calcium concentration ([Ca2+]i) was examined in a unique axial-symmetrical model that focuses on spine–dendrite interactions, and the simulations of the model were compared with the behavior of real dendritic spines in cultured hippocampal neurons. A set of nonlinear differential equations describes the behavior of a spherical dendritic spine head, linked to a dendrite via a cylindrical spine neck. Mechanisms for handling of calcium (including internal stores, buffers, and efflux pathways) are placed in both the dendrites and spines. In response to a calcium surge, the magnitude and time course of the response in both the spine and the parent dendrite vary as a function of the length of the spine neck such that a short neck increases the magnitude of the response in the dendrite and speeds up the recovery in the spine head. The generality of the model, originally constructed for a case of release of calcium from stores, was tested in simulations of fast calcium influx through membrane channels and verified the impact of spine neck on calcium dynamics. Spatiotemporal distributions of [Ca2+]i, measured in individual dendritic spines of cultured hippocampal neurons injected with Calcium Green-1, were monitored with a confocal laser scanning microscope. Line scans of spines and dendrites at a <1-ms time resolution reveal simultaneous transient rises in [Ca2+]i in spines and their parent dendrites after application of caffeine or during spontaneous calcium transients associated with synaptic or action potential discharges. The magnitude of responses in the individual compartments, spine–dendrite disparity, and the temporal distribution of [Ca2+]i were different for spines with short and long necks, with the latter being more independent of the dendrite, in agreement with prediction of the model.

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Proteomic identification of phosphorylation dependent Septin 7 interactors that drive dendritic spine formation

10.1101/2022.01.04.474970 ◽

2022 ◽

Author(s):

Smita Yadav ◽

Sujin Byeon ◽

Bailey Werner ◽

Reilly Falter ◽

Kristian Davidsen ◽

...

Keyword(s):

Dendritic Spine ◽

Neuronal Development ◽

Cytoskeletal Proteins ◽

Spine Formation ◽

Spine Head ◽

Biochemical Assays ◽

Physiological Regulator ◽

Synapse Maturation ◽

Proteomic Identification ◽

Mechanistic Basis

Septins are a family of cytoskeletal proteins that regulate several important aspects of neuronal development. Septin 7 (Sept7) is enriched at the base of dendritic spines in excitatory neurons and mediates both spine formation and spine-synapse maturation. Phosphorylation at a conserved C-terminal tail residue of Sept7 mediates its translocation into the dendritic spine head to allow spine-synapse maturation. The mechanistic basis for postsynaptic stability and compartmentalization conferred by phosphorylated Sept7, however, is not known. We report herein the proteomic identification of Sept7 phosphorylation dependent neuronal interactors. Using Sept7 C-terminal phosphopeptide pulldown and biochemical assays, we show that the 14-3-3 family of proteins specifically interact with Sept7 when phosphorylated at the T426 residue. Biochemically, we validate the interaction between Sept7 and 14-3-3 isoform gamma, and show that 14-3-3 gamma is also enriched in mature dendritic spine head. Further, we demonstrate that interaction of phosphorylated Sept7 with 14-3-3 protects it from dephosphorylation, as expression of a 14-3-3 antagonist significantly decreases phosphorylated Sept7 in neurons. This study identifies 14-3-3 proteins as an important physiological regulator of Sept7 function in neuronal development.

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