Differential Scaling of Synaptic Molecules within Functional Zones of an Excitatory Synapse during Homeostatic Plasticity

Venkatesan, Sridevi; Subramaniam, Sandhya; Rajeev, Premchand; Chopra, Yukti; Jose, Mini; Nair, Deepak

doi:10.1523/eneuro.0407-19.2020

Cited by 23 publications

(23 citation statements)

References 45 publications

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“…Over the last decade, several studies have shown that individual synapses are heterogeneous structures where nanoscale segregation of synaptic molecules on the membrane plays a crucial role in synaptic transmission and plasticity ( Chen et al., 2018 ; Dani et al., 2010 ; Nair et al., 2013 ; Venkatesan et al., 2020 ). Despite the functional overlap of amyloidogenic machinery, such evaluations on its subsynaptic organization have not yet been addressed in detail ( Almeida et al., 2005 ; Muller et al., 2017 ; Snyder et al., 2005 ).…”

Section: Discussionmentioning

confidence: 99%

Alteration in synaptic nanoscale organization dictates amyloidogenic processing in Alzheimer's disease

et al. 2021

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Section: Discussionmentioning

confidence: 99%

Alteration in synaptic nanoscale organization dictates amyloidogenic processing in Alzheimer's disease

et al. 2021

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“…In addition, a role for this zone in mediating short‐ and long‐term plasticity has been suggested (Monday et al., 2018; Sudhof, 2012). The morphology of active zone directly correlates with synaptic efficacy, where larger active zone is indicative of more synaptic vesicles and stronger synapses, which can produce stronger electric currents (Michel et al., 2015; Sudhof, 2012; Venkatesan et al., 2020). Age‐related increases in the length of active zone in adult rats may be reflective of ongoing maturation of circuitries during this period of life, which is lost during later life stages, thus, rendering the individual more susceptible to behavioral changes including anxiety.…”

Section: Discussionmentioning

confidence: 99%

Age‐related behavioral and ultrastructural changes in the rat amygdala

Lomidze¹,

Zhvania²,

Tizabi

et al. 2020

Developmental Neurobiology

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Although the relationships between brain structure and emotions may alter across the life span, this relationship is of particular importance during aging when significant alterations in emotions may be manifested. Understanding the structural–behavioral relationship could not only provide a neurobiological basis of these changes, but could also suggest potential intervention. Since anxiety is commonly observed in aging population, we undertook this study to determine the extent of this behavioral manifestations as well as the associated ultrastructural changes in the amygdala. Rats of various age groups, adolescent, adult, and aged were tested for anxiety‐like behavior and the ultrastructure/presynaptic architecture of the central nucleus of amygdala (CNA) were evaluated using transmission electron microscopy (EM). Aged rats were consistently more anxious than the other groups as evidenced by their scores in the elevated plus maze. Morphometric EM analysis of axodendritic synapses revealed that the aged rats had a lower presynaptic area as well as number of synapses, but unexpectedly a higher number of presynaptic mitochondria in CNA. Since presynaptic mitochondria are known to provide the energy for neurotransmission, it may be concluded that compensatory mechanisms are still operational during aging, and hence, may be a target for therapeutic intervention at this stage of life span.

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“…Synaptic scaling via changes in post-synaptic receptor complement is common in homeostatic plasticity, including in cortical pyramidal neurons (Maffei and Turrigiano, 2008; Turrigiano, 2008; Gainey et al, 2009; Keck et al, 2013; Fernandes and Carvalho, 2016; Teichert et al, 2017; Chowdhury and Hell, 2018; Venkatesan et al, 2020). However, using optogenetic activation of RCG axons in acute dLGN slices, we did not observe any change in the amplitude of mEPSCs or I AMPA /I NMDA indicating that there were no detectable changes in the number and/or composition of post-synaptic AMPARs following enucleation.…”

Section: Discussionmentioning

confidence: 99%

Structural and functional plasticity in the dorsolateral geniculate nucleus of mice following bilateral enucleation

Bhandari

SMITH

Hook

2020

Preprint

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Within the nervous system, homeostatic mechanisms stabilize network activity following disruption by injury, disease, or degeneration. Vision loss and optic nerve injury in age-related diseases such as glaucoma might trigger homeostatic responses in direct retinal projection targets in the brain in adulthood. We tested this possibility using patch-clamp electrophysiology, optogenetics, and single-cell dendritic analysis to probe the effects of optic nerve injury and vision loss on dLGN thalamocortical (TC) relay neurons and their synaptic inputs following bilateral enucleation. Using vGlut2 immunostaining, we found that retinal axon terminals in the dLGN degenerated over several days post-enucleation, which corresponded with the loss of retinogeniculate (RG) synaptic function as assessed with optogenetic stimulation of ganglion cell axons in acute brain slices. Analysis of TC neuron dendritic structure from single-cell dye fills revealed a gradual loss of dendrites proximal to the soma, where TC neurons receive the bulk of RG inputs. Surprisingly, there was little change to the frequency of miniature post-synaptic currents (mEPSCs), even two weeks post-enucleation, although we did find an increase in the relative proportion of mEPSCs with slower kinetics, hinting at a possible enhancement of corticogeniculate input. Whole-cell current clamp recordings showed that enucleation enhanced TC neuron action potential firing and input resistance, consistent with homeostatic scaling of intrinsic neuronal excitability following perturbation of synaptic inputs. Our findings show that degeneration of the retinal axons/optic nerve and loss of RG synaptic inputs induces structural and functional changes in TC neurons consistent with compensatory homeostatic plasticity in the dLGN.

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Differential Scaling of Synaptic Molecules within Functional Zones of an Excitatory Synapse during Homeostatic Plasticity

Cited by 23 publications

References 45 publications

Alteration in synaptic nanoscale organization dictates amyloidogenic processing in Alzheimer's disease

Alteration in synaptic nanoscale organization dictates amyloidogenic processing in Alzheimer's disease

Age‐related behavioral and ultrastructural changes in the rat amygdala

Structural and functional plasticity in the dorsolateral geniculate nucleus of mice following bilateral enucleation

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