Permissive proteolytic activity for visual cortical plasticity

Mataga, Nobuko; Nagai, Nobuo; Hensch, Takao K.

doi:10.1073/pnas.102088899

Cited by 160 publications

(114 citation statements)

References 41 publications

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“…Although they appear as the ideal synaptic substrate for CP plasticity and their maturation correlates with sensory experience (10,25), it has not been experimentally tested whether maturation of silent synapses indeed causes the termination of critical periods. This conceptual model contrasts with the current view that increased local inhibition and the expression of plasticity brakes ends critical periods (18)(19)(20)26).…”

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confidence: 46%

“…Among these, the developmental increase of local inhibition appears to be the dominating mechanism to regulate cortical plasticity and CPs (15)(16)(17). Additionally, extracellular matrix remodeling is involved, as well as receptors of immune signaling, such as paired Ig-like receptor B (PirB), or axon pathfinding, such as Nogo (18)(19)(20)(21). However, a specific function to directly regulate synapse remodeling during initial neural network optimization is not known and a potential instructive function of PirB was described for adult cortical plasticity but not plasticity of the initial synapse remodeling during CPs (22).…”

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confidence: 99%

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Progressive maturation of silent synapses governs the duration of a critical period

Huang

Stodieck

Goetze

et al. 2015

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

172

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During critical periods, all cortical neural circuits are refined to optimize their functional properties. The prevailing notion is that the balance between excitation and inhibition determines the onset and closure of critical periods. In contrast, we show that maturation of silent glutamatergic synapses onto principal neurons was sufficient to govern the duration of the critical period for ocular dominance plasticity in the visual cortex of mice. Specifically, postsynaptic density protein-95 (PSD-95) was absolutely required for experience-dependent maturation of silent synapses, and its absence before the onset of critical periods resulted in lifelong juvenile ocular dominance plasticity. Loss of PSD-95 in the visual cortex after the closure of the critical period reinstated silent synapses, resulting in reopening of juvenile-like ocular dominance plasticity. Additionally, silent synapse-based ocular dominance plasticity was largely independent of the inhibitory tone, whose developmental maturation was independent of PSD-95. Moreover, glutamatergic synaptic transmission onto parvalbumin-positive interneurons was unaltered in PSD-95 KO mice. These findings reveal not only that PSD-95-dependent silent synapse maturation in visual cortical principal neurons terminates the critical period for ocular dominance plasticity but also indicate that, in general, once silent synapses are consolidated in any neural circuit, initial experience-dependent functional optimization and critical periods end.

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confidence: 46%

mentioning

confidence: 99%

Progressive maturation of silent synapses governs the duration of a critical period

Huang

Stodieck

Goetze

et al. 2015

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

172

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“…However, in the absence of GAD 65 , the active site of VGAT will become available to cytosolic GABA, and vesicular transport of GABA can be restored to a certain extent. This proposed mechanism can explain the observation that GAD 65 knockout mice can survive and grow relatively normal, except with signs of deficiencies in GABA transmission such as increase in seizure susceptibility (28), absence of long-term depression (29), increase in anxiety-like behavior (30,31), and lack of cortical plasticity (32). However, GAD 67 knockout is lethal.…”

Section: Discussionmentioning

confidence: 99%

Demonstration of functional coupling between γ-aminobutyric acid (GABA) synthesis and vesicular GABA transport into synaptic vesicles

Osterhaus

et al. 2003

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

218

204

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L-Glutamic acid decarboxylase (GAD) exists as both membraneassociated and soluble forms in the mammalian brain. Here, we propose that there is a functional and structural coupling between the synthesis of ␥-aminobutyric acid (GABA) by membraneassociated GAD and its packaging into synaptic vesicles (SVs) by vesicular GABA transporter (VGAT). This notion is supported by the following observations. First, newly synthesized [ 3 H]GABA from [ 3 H]L-glutamate by membrane-associated GAD is taken up preferentially over preexisting GABA by using immunoaffinity-purified GABAergic SVs. Second, the activity of SV-associated GAD and VGAT seems to be coupled because inhibition of GAD also decreases VGAT activity. Third, VGAT and SV-associated Ca 2؉ ͞ calmodulin-dependent kinase II have been found to form a protein complex with GAD. A model is also proposed to link the neuronal stimulation to enhanced synthesis and packaging of GABA into SVs.T he rate-limiting enzyme L-glutamic acid decarboxylase (GAD, EC 4.1.1.15) is involved in the synthesis of ␥-aminobutyric acid (GABA), a major inhibitory neurotransmitter in the mammalian brain. There are two well-characterized GAD isoforms in the human brain, namely GAD 65 and GAD 67 (referring to GAD with a molecular mass of 65 kDa and 67 kDa, respectively) (1). Both GAD 65 and GAD 67 are present as homodimers or heterodimers in soluble GAD (SGAD) and membrane-associated GAD (MGAD) pools (2-4). The ratio of GAD 65 to GAD 67 is higher in synaptic vesicle (SV) fractions than in the cytosol (5). Some studies suggest that GAD 65 binds to the membranes (6, 7) and that GAD 67 subsequently interacts with MGAD 65 (2, 6). However, the nature of anchorage of GAD to membranes and its physiological significance is still not well understood. GAD is not considered to be an integral membrane protein because it lacks a stretch of hydrophobic amino acids long enough to span the membrane. Subpopulations of GAD 65 and GAD 67 remain firmly anchored to membranes despite various ionic extraction methods (2,4,8). The interaction of GAD with membranes was reported to be through ionic (9-11), hydrophobic (12, 13), protein phosphorylation (14), or proteinprotein interaction (15). Previously, we reported that MGAD is activated by phosphorylation that requires an electrochemical gradient across the SV membrane (7). A model for the anchoring mechanism of GAD to SV and its role as a link between GABA synthesis and storage in nerve terminals was also proposed (15). The evidence presented here will demonstrate that GABA synthesized by SV-associated GAD is preferentially transported into the SV by vesicular GABA transporters (VGATs). We have also demonstrated that VGAT, a 10-transmembrane helix protein (16), forms a protein complex with GAD on the SV and could be involved in the anchorage of MGAD to the SV. The formation of this GAD protein complex ensures an efficient coupling between GABA synthesis and packaging into the SV. Materials and MethodsPreparation of SVs. SVs were purified from whole rat brain (Sprague-Dawle...

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“…T he extracellular matrix (EM) is a crucial determinant of cortical plasticity and the effects of extracellular proteases on the activity-dependent rearrangement of cortical circuitry have long been recognized [1][2][3][4] . The direct link with plasticity is stressed by the activity-regulated maturation of EM [5][6][7] ending in parallel with the closure of the juvenile critical period of heightened plasticity 6,8 .…”

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confidence: 99%

Extracellular matrix inhibits structural and functional plasticity of dendritic spines in the adult visual cortex

et al. 2013

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Brain cells are immersed in a complex structure forming the extracellular matrix. The composition of the matrix gradually matures during postnatal development, as the brain circuitry reaches its adult form. The fully developed extracellular environment stabilizes neuronal connectivity and decreases cortical plasticity as highlighted by the demonstration that treatments degrading the matrix are able to restore synaptic plasticity in the adult brain. The mechanisms through which the matrix inhibits cortical plasticity are not fully clarified. Here we show that a prominent component of the matrix, chondroitin sulfate proteoglycans (CSPGs), restrains morphological changes of dendritic spines in the visual cortex of adult mice. By means of in vivo and in vitro two-photon imaging and electrophysiology, we find that after enzymatic digestion of CSPGs, cortical spines become more motile and express a larger degree of structural and functional plasticity.

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Permissive proteolytic activity for visual cortical plasticity

Cited by 160 publications

References 41 publications

Progressive maturation of silent synapses governs the duration of a critical period

Progressive maturation of silent synapses governs the duration of a critical period

Demonstration of functional coupling between γ-aminobutyric acid (GABA) synthesis and vesicular GABA transport into synaptic vesicles

Extracellular matrix inhibits structural and functional plasticity of dendritic spines in the adult visual cortex

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