Illuminating Relationships Between the Pre- and Post-synapse

Sanderson, Thomas M.; Georgiou, John; Collingridge, Graham L.

doi:10.3389/fncir.2020.00009

Cited by 9 publications

(6 citation statements)

References 146 publications

(230 reference statements)

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“…In our model, we assumed the same growth rule for both boutons and spines. This is in line with experimental observations suggesting that pre-and postsynaptic plasticity are regulated in an orchestrated way (Ehrlich et al, 2007;Letellier et al, 2019;Sanderson et al, 2020). The upregulation of VGLUT1 and PSD-95 at 24 h indicates that the functional synaptic transmission among the stimulated neurons is also enhanced.…”

Section: Discussionsupporting

confidence: 91%

Time course of homeostatic structural plasticity in response to optogenetic stimulation in mouse anterior cingulate cortex

Han

Gallinaro

Normann

et al. 2020

Preprint

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Synapse formation and network rewiring is key to build neural circuits during development and has been widely observed in adult brains. Maintaining neural activity with the help of synaptic plasticity is essential to enable normal brain function. The model of homeostatic structural plasticity (HSP) was proposed to reflect the homeostatic regulation of neural activity and explain structural changes seen after perturbations. However, the specific temporal profile of such plastic responses has not yet been elucidated in experiments. To address this issue, we combined computational modeling and mouse optogenetic stimulation experiments. Our model predicted that within 48 h post-stimulation, neural activity returns to baseline, while the connectivity among stimulated neurons follows a very specific transient increase and decrease. To capture such dynamics experimentally in vivo, we activated the pyramidal neurons in the anterior cingulate cortex of mice and harvested their brains at 1.5 h, 24 h, and 48 h post-stimulation. Cortical hyperactivity as demonstrated by robust c-Fos expression persisted up to 1.5 h and decayed to baseline after 24 h. However, spine density and spine head volume were increased at 24 h and decreased at 48 h. Synaptic proteins VGLUT1 and PSD-95 were also upregulated and downregulated at 24 h and 48 h, respectively, while the calmodulin-binding protein neurogranin was translocated from the soma to the dendrite. Additionally, lasting astrocyte reactivation and microglia proliferation were observed, suggesting a role of neuron-glia interaction. All this corroborates the interpretation of our experimental results in terms of homeostatic structural plasticity. Our results bring important insights of how external stimulation modulates synaptic plasticity and behaviors.Significance StatementWe combined both computational modeling and mouse experiments to clarify the temporal dynamics of structural and functional homeostatic plasticity in response to external stimulation. We observed the biphasic regulation of spine density, spine head volume, and synaptic proteins at 24 h and 48 h after the optogenetic stimulation of the anterior cingulate cortex, when the neural activity was restored to the homeostatic level. The orchestrated regulation of presynaptic VGLUT1 and postsynaptic PSD-95, as well as the soma-dendrites translocation of neurogranin, suggested an elaborate molecular mechanism underlying homeostatic structural plasticity. Our experimental results thus corroborated the theoretical concept of homeostatic structural plasticity and revealed the temporal evolution of structural and functional plasticity.

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Section: Discussionsupporting

confidence: 91%

Time course of homeostatic structural plasticity in response to optogenetic stimulation in mouse anterior cingulate cortex

Han

Gallinaro

Normann

et al. 2020

Preprint

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“…All these observations point to a biphasic regulation of synaptic strength within 48 h and an orchestrated regulation of presynaptic and postsynaptic plasticity after stimulation, as reported before by others (Ehrlich et al 2007;Letellier et al 2019;Sanderson et al 2020). The results of neural morphology analysis were in line with our observations in synaptic proteins.…”

Section: A Computational Model Of Stimulation-induced Homeostatic Structural Plasticitysupporting

confidence: 91%

Time Course of Homeostatic Structural Plasticity in Response to Optogenetic Stimulation in Mouse Anterior Cingulate Cortex

et al. 2021

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Plasticity is the mechanistic basis of development, aging, learning, and memory, both in healthy and pathological brains. Structural plasticity is rarely accounted for in computational network models due to a lack of insight into the underlying neuronal mechanisms and processes. Little is known about how the rewiring of networks is dynamically regulated. To inform such models, we characterized the time course of neural activity, the expression of synaptic proteins, and neural morphology employing an in vivo optogenetic mouse model. We stimulated pyramidal neurons in the anterior cingulate cortex of mice and harvested their brains at 1.5 h, 24 h, and $48\,\mathrm{h}$ after stimulation. Stimulus-induced cortical hyperactivity persisted up to 1.5 h and decayed to baseline after $24\,\mathrm{h}$ indicated by c-Fos expression. The synaptic proteins VGLUT1 and PSD-95, in contrast, were upregulated at $24\,\mathrm{h}$ and downregulated at $48\,\mathrm{h}$, respectively. Spine density and spine head volume were also increased at $24\,\mathrm{h}$ and decreased at $48\,\mathrm{h}$. This specific sequence of events reflects a continuous joint evolution of activity and connectivity that is characteristic of the model of homeostatic structural plasticity. Our computer simulations thus corroborate the observed empirical evidence from our animal experiments.

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“…The size and functionality of the pre and postsynapse are correlated ( Sanderson et al, 2020 ) in part through activity-dependent regulation of group I mGluR receptors ( Sanderson et al, 2018 ). If both the presynaptic and postsynaptic mechanisms occur at the same subset of low P(r) synapses it is possible that they could play a role in maintaining pre and postsynaptic complementarity when induced together.…”

Section: Discussionmentioning

confidence: 99%

Selective Recruitment of Presynaptic and Postsynaptic Forms of mGluR-LTD

Sanderson

Ralph

Amici

et al. 2022

Front. Synaptic Neurosci.

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In area CA1 of the hippocampus, long-term depression (LTD) can be induced by activating group I metabotropic glutamate receptors (mGluRs), with the selective agonist DHPG. There is evidence that mGluR-LTD can be expressed by either a decrease in the probability of neurotransmitter release [P(r)] or by a change in postsynaptic AMPA receptor number. However, what determines the locus of expression is unknown. We investigated the expression mechanisms of mGluR-LTD using either a low (30 μM) or a high (100 μM) concentration of (RS)-DHPG. We found that 30 μM DHPG generated presynaptic LTD that required the co-activation of NMDA receptors, whereas 100 μM DHPG resulted in postsynaptic LTD that was independent of the activation of NMDA receptors. We found that both forms of LTD occur at the same synapses and that these may constitute the population with the lowest basal P(r). Our results reveal an unexpected complexity to mGluR-mediated synaptic plasticity in the hippocampus.

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Illuminating Relationships Between the Pre- and Post-synapse

Cited by 9 publications

References 146 publications

Time course of homeostatic structural plasticity in response to optogenetic stimulation in mouse anterior cingulate cortex

Time course of homeostatic structural plasticity in response to optogenetic stimulation in mouse anterior cingulate cortex

Time Course of Homeostatic Structural Plasticity in Response to Optogenetic Stimulation in Mouse Anterior Cingulate Cortex

Selective Recruitment of Presynaptic and Postsynaptic Forms of mGluR-LTD

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