scholarly journals Spine dynamics of PSD-95-deficient neurons in the visual cortex link silent synapses to structural cortical plasticity

2021 ◽  
Vol 118 (10) ◽  
pp. e2022701118
Author(s):  
Rashad Yusifov ◽  
Anja Tippmann ◽  
Jochen F. Staiger ◽  
Oliver M. Schlüter ◽  
Siegrid Löwel
Keyword(s):  
Visual Cortex ◽  
Cortical Neurons ◽  
Structural Plasticity ◽  
Monocular Deprivation ◽  
Functional Link ◽  
Silent Synapses ◽  
Layer 2 ◽  
Synapse Maturation ◽  
Silent Synapse ◽  
Spine Dynamics

Critical periods (CPs) are time windows of heightened brain plasticity during which experience refines synaptic connections to achieve mature functionality. At glutamatergic synapses on dendritic spines of principal cortical neurons, the maturation is largely governed by postsynaptic density protein-95 (PSD-95)-dependent synaptic incorporation of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors into nascent AMPA-receptor silent synapses. Consequently, in mouse primary visual cortex (V1), impaired silent synapse maturation in PSD-95-deficient neurons prevents the closure of the CP for juvenile ocular dominance plasticity (jODP). A structural hallmark of jODP is increased spine elimination, induced by brief monocular deprivation (MD). However, it is unknown whether impaired silent synapse maturation facilitates spine elimination and also preserves juvenile structural plasticity. Using two-photon microscopy, we assessed spine dynamics in apical dendrites of layer 2/3 pyramidal neurons (PNs) in binocular V1 during ODP in awake adult mice. Under basal conditions, spine formation and elimination ratios were similar between PSD-95 knockout (KO) and wild-type (WT) mice. However, a brief MD affected spine dynamics only in KO mice, where MD doubled spine elimination, primarily affecting newly formed spines, and caused a net reduction in spine density similar to what has been observed during jODP in WT mice. A similar increase in spine elimination after MD occurred if PSD-95 was knocked down in single PNs of layer 2/3. Thus, structural plasticity is dictated cell autonomously by PSD-95 in vivo in awake mice. Loss of PSD-95 preserves hallmark features of spine dynamics in jODP into adulthood, revealing a functional link of PSD-95 for experience-dependent synapse maturation and stabilization during CPs.

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

2015 ◽  
Vol 112 (24) ◽  
pp. E3131-E3140 ◽  
Author(s):  
Xiaojie Huang ◽  
Sophia K. Stodieck ◽  
Bianka Goetze ◽  
Lei Cui ◽  
Man Ho Wong ◽  
...  
Keyword(s):  
Visual Cortex ◽  
Critical Period ◽  
Neural Circuit ◽  
Ocular Dominance ◽  
Critical Periods ◽  
Ocular Dominance Plasticity ◽  
Silent Synapses ◽  
Synapse Maturation ◽  
Silent Synapse ◽  
Visual Cortical

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.

scholarly journals IGF-1 Restores Visual Cortex Plasticity in Adult Life by Reducing Local GABA Levels

2012 ◽  
Vol 2012 ◽  
pp. 1-10 ◽  
Author(s):  
José Fernando Maya-Vetencourt ◽  
Laura Baroncelli ◽  
Alessandro Viegi ◽  
Ettore Tiraboschi ◽  
Eero Castren ◽  
...  
Keyword(s):  
Nervous System ◽  
Visual Cortex ◽  
Neural Plasticity ◽  
Cortical Neurons ◽  
Environmental Enrichment ◽  
Adult Life ◽  
Monocular Deprivation ◽  
Adult Brain ◽  
Environmental Stimulation ◽  
The Central Nervous System

The central nervous system architecture is markedly modified by sensory experience during early life, but a decline of plasticity occurs with age. Recent studies have challenged this dogma providing evidence that both pharmacological treatments and paradigms based on the manipulation of environmental stimulation levels can be successfully employed as strategies for enhancing plasticity in the adult nervous system. Insulin-like growth factor 1 (IGF-1) is a peptide implicated in prenatal and postnatal phases of brain development such as neurogenesis, neuronal differentiation, synaptogenesis, and experience-dependent plasticity. Here, using the visual system as a paradigmatic model, we report that IGF-1 reactivates neural plasticity in the adult brain. Exogenous administration of IGF-1 in the adult visual cortex, indeed, restores the susceptibility of cortical neurons to monocular deprivation and promotes the recovery of normal visual functions in adult amblyopic animals. These effects were accompanied by a marked reduction of intracortical GABA levels. Moreover, we show that a transitory increase of IGF-1 expression is associated to the plasticity reinstatement induced by environmental enrichment (EE) and that blocking IGF-1 action by means of the IGF-1 receptor antagonist JB1 prevents EE effects on plasticity processes.

scholarly journals Dark Rearing Promotes the Recovery of Visual Cortical Responses but Not the Morphology of Geniculocortical Axons in Amblyopic Cat

2021 ◽  
Vol 15 ◽  
Author(s):  
Takahiro Gotou ◽  
Katsuro Kameyama ◽  
Ayane Kobayashi ◽  
Kayoko Okamura ◽  
Takahiko Ando ◽  
...  
Keyword(s):  
Visual Cortex ◽  
Cortical Neurons ◽  
Visual Pathway ◽  
Monocular Deprivation ◽  
Postnatal Life ◽  
Visual Neurons ◽  
Cortical Responses ◽  
Soma Size ◽  
Visual Cortical ◽  
Dark Rearing

Monocular deprivation (MD) of vision during early postnatal life induces amblyopia, and most neurons in the primary visual cortex lose their responses to the closed eye. Anatomically, the somata of neurons in the closed-eye recipient layer of the lateral geniculate nucleus (LGN) shrink and their axons projecting to the visual cortex retract. Although it has been difficult to restore visual acuity after maturation, recent studies in rodents and cats showed that a period of exposure to complete darkness could promote recovery from amblyopia induced by prior MD. However, in cats, which have an organization of central visual pathways similar to humans, the effect of dark rearing only improves monocular vision and does not restore binocular depth perception. To determine whether dark rearing can completely restore the visual pathway, we examined its effect on the three major concomitants of MD in individual visual neurons, eye preference of visual cortical neurons and soma size and axon morphology of LGN neurons. Dark rearing improved the recovery of visual cortical responses to the closed eye compared with the recovery under binocular conditions. However, geniculocortical axons serving the closed eye remained retracted after dark rearing, whereas reopening the closed eye restored the soma size of LGN neurons. These results indicate that dark rearing incompletely restores the visual pathway, and thus exerts a limited restorative effect on visual function.

scholarly journals The Corpus Callosum and the Visual Cortex: Plasticity Is a Game for Two

2012 ◽  
Vol 2012 ◽  
pp. 1-10 ◽  
Author(s):  
Marta Pietrasanta ◽  
Laura Restani ◽  
Matteo Caleo
Keyword(s):  
Visual Cortex ◽  
Corpus Callosum ◽  
Cortical Neurons ◽  
Life Experience ◽  
Monocular Deprivation ◽  
Major Pathway ◽  
Dependent Plasticity ◽  
Ideal System ◽  
Study Experience ◽  
Brain Functional Connectivity

Throughout life, experience shapes and selects the most appropriate brain functional connectivity to adapt to a changing environment. An ideal system to study experience-dependent plasticity is the visual cortex, because visual experience can be easily manipulated. In this paper, we focus on the role of interhemispheric, transcallosal projections in experience-dependent plasticity of the visual cortex. We review data showing that deprivation of sensory experience can modify the morphology of callosal fibres, thus altering the communication between the two hemispheres. More importantly, manipulation of callosal input activity during an early critical period alters developmental maturation of functional properties in visual cortex and modifies its ability to remodel in response to experience. We also discuss recent data in rat visual cortex, demonstrating that the corpus callosum plays a role in binocularity of cortical neurons and is involved in the plastic shift of eye preference that follows a period of monocular eyelid suture (monocular deprivation) in early age. Thus, experience can modify the fine connectivity of the corpus callosum, and callosal connections represent a major pathway through which experience can mediate functional maturation and plastic rearrangements in the visual cortex.

scholarly journals Precise levels of nectin-3 are required for proper synapse formation in postnatal visual cortex

2020 ◽  
Vol 15 (1) ◽  
Author(s):  
Johanna Tomorsky ◽  
Philip R. L. Parker ◽  
Chris Q. Doe ◽  
Cristopher M. Niell
Keyword(s):  
Visual Cortex ◽  
Dendritic Spine ◽  
Cortical Neurons ◽  
Synapse Formation ◽  
Ocular Dominance ◽  
Developmental Time ◽  
Basal Dendrites ◽  
Layer 2 ◽  
Eye Opening ◽  
Visual Cortical

Abstract Background Developing cortical neurons express a tightly choreographed sequence of cytoskeletal and transmembrane proteins to form and strengthen specific synaptic connections during circuit formation. Nectin-3 is a cell-adhesion molecule with previously described roles in synapse formation and maintenance. This protein and its binding partner, nectin-1, are selectively expressed in upper-layer neurons of mouse visual cortex, but their role in the development of cortical circuits is unknown. Methods Here we block nectin-3 expression (via shRNA) or overexpress nectin-3 in developing layer 2/3 visual cortical neurons using in utero electroporation. We then assay dendritic spine densities at three developmental time points: eye opening (postnatal day (P)14), one week following eye opening after a period of heightened synaptogenesis (P21), and at the close of the critical period for ocular dominance plasticity (P35). Results Knockdown of nectin-3 beginning at E15.5 or ~ P19 increased dendritic spine densities at P21 or P35, respectively. Conversely, overexpressing full length nectin-3 at E15.5 decreased dendritic spine densities when all ages were considered together. The effects of nectin-3 knockdown and overexpression on dendritic spine densities were most significant on proximal secondary apical dendrites. Interestingly, an even greater decrease in dendritic spine densities, particularly on basal dendrites at P21, was observed when we overexpressed nectin-3 lacking its afadin binding domain. Conclusion These data collectively suggest that the proper levels and functioning of nectin-3 facilitate normal synapse formation after eye opening on apical and basal dendrites in layer 2/3 of visual cortex.

Genetic instructions and developmental plasticity in the kitten’s visual cortex

1977 ◽  
Vol 278 (961) ◽  
pp. 425-434 ◽  
Keyword(s):  
Visual Cortex ◽  
Cortical Neurons ◽  
Developmental Plasticity ◽  
Ocular Dominance ◽  
Retrograde Transport ◽  
Monocular Deprivation ◽  
Neutral Density Filter ◽  
Density Filter ◽  
Adult Cat ◽  
Genetic Instructions

Two major properties of neurons in the kitten’s visual cortex, binocularity and orientation selectivity, are present when the eyes first open, and therefore can be established by genetic instructions alone. However, both of these attributes require visual experience for their maintenance or strengthening; and both can be rapidly modified by unusual kinds of experience. Alternating sequences of cells dominated by one eye, then the other, can be recorded during penetrations through the cortex in binocularly deprived kittens, typical of the ‘ocular dominance columns’ of the normal adult cat. However, if one eye is deprived by lid-suture, the entire visual cortex becomes strongly dominated by the open eye. Experiments in which each eye saw separately through a transparent neutral density filter or a translucent diffuser showed that this phenomenon is caused not by the reduction in retinal illumination, but by the abolition of contrast in the deprived eye. A study of the retrograde transport of horseradish peroxidase from the visual cortex to the principal laminae of the lateral geniculate nucleus suggested that monocular deprivation from early in life may lead to a gross reduction in the distribution of afferent fibres from the deprived laminae. Previous experiments have found that if a kitten is exposed only to contours of one orientation, its cortical neurons become modified in their distribution of preferred orientations. This phenomenon was re-confirmed in a new study using a rigorously objective method of analysis.

scholarly journals Precise levels of Nectin-3 and an interaction with Afadin are required for proper synapse formation in postnatal visual cortex

2019 ◽  
Author(s):  
Johanna Tomorsky ◽  
Philip R. L. Parker ◽  
Chris Q. Doe ◽  
Cristopher M. Niell
Keyword(s):  
Visual Cortex ◽  
Dendritic Spine ◽  
Cortical Neurons ◽  
Synapse Formation ◽  
Ocular Dominance ◽  
Developmental Time ◽  
Ocular Dominance Plasticity ◽  
Layer 2 ◽  
Eye Opening ◽  
Visual Cortical

AbstractBackgroundDeveloping cortical neurons express a tightly choreographed sequence of cytoskeletal and transmembrane proteins to form and strengthen specific synaptic connections during circuit formation. Nectin-3 is a cell-adhesion molecule with previously described roles in synapse formation and maintenance. This protein and its binding partner, Nectin-1, are selectively expressed in upper-layer neurons of mouse visual cortex, but their role in the development of cortical circuits is unknown.MethodsHere we block Nectin-3 expression (via shRNA) or overexpress Nectin-3 in developing layer 2/3 visual cortical neurons using in utero electroporation. We then assay dendritic spine densities at three developmental time points: eye opening (postnatal day (P)14), one week following eye opening after a period of heightened synaptogenesis (P21), and at the close of the critical period for ocular dominance plasticity (P35).ResultsKnockdown of Nectin-3 beginning at E15.5 or ∼P19 increased dendritic spine densities at P21 or P35, respectively. Conversely, overexpressing full length Nectin-3 at E15.5 led to decreased dendritic spine densities when all ages were considered together. Interestingly, an even greater decrease in dendritic spine densities, particularly at P21, was observed when we overexpressed Nectin-3 lacking its Afadin binding domain, indicating Afadin may facilitate spine morphogenesis after eye opening.ConclusionThese data collectively suggest that the proper levels of Nectin-3, as well as the interaction of Nectin-3 with Afadin, facilitate normal synapse formation after eye opening in layer 2/3 visual cortical neurons.

Silent synapses persist into adulthood in layer 2/3 pyramidal neurons of visual cortex in dark-reared mice

2013 ◽  
Vol 109 (8) ◽  
pp. 2064-2076 ◽  
Author(s):  
Rie Funahashi ◽  
Takuro Maruyama ◽  
Yumiko Yoshimura ◽  
Yukio Komatsu
Keyword(s):  
Visual Cortex ◽  
Ampa Receptors ◽  
Pyramidal Neurons ◽  
Receptor Activation ◽  
Excitatory Synapses ◽  
Brain Functions ◽  
Silent Synapses ◽  
Visual Inputs ◽  
Layer 2 ◽  
Dark Rearing

Immature excitatory synapses often have NMDA receptors but not AMPA receptors in central neurons, including visual cortical pyramidal neurons. These synapses, called silent synapses, are converted to functional synapses with AMPA receptors by NMDA receptor activation during early development. It is likely that this process underlies the activity-dependent refinement of neuronal circuits and brain functions. In the present study, we investigated postnatal development of excitatory synapses, focusing on the role of visual inputs in the conversion of silent to functional synapses in mouse visual cortex. We analyzed presumably unitary excitatory postsynaptic currents (EPSCs) between a pair of layer 2/3 pyramidal neurons, using minimal stimulation with a patch pipette attached to the soma of one of the pair. The proportion of silent synapses was estimated by the difference in the failure rate between AMPA- and NMDA-EPSCs. In normal development, silent synapses were present abundantly before eye opening, decreased considerably by the critical period of ocular dominance plasticity, and almost absent in adulthood. This decline in silent synapses was prevented by dark rearing. The amplitude of presumably unitary AMPA-EPSCs increased with age, but this increase was suppressed by dark rearing. The quantal amplitude of AMPA-EPSCs and paired-pulse ratio of NMDA-EPSCs both remained unchanged during development, independent of visual experience. These results indicate that visual inputs are required for the conversion of silent to functional synapses and this conversion largely contributes to developmental increases in the amplitude of presumably unitary AMPA-EPSCs.

scholarly journals Experience-dependent structural plasticity at pre- and postsynaptic sites of layer 2/3 cells in developing visual cortex

2019 ◽  
Author(s):  
Yujiao Jennifer Sun ◽  
J. Sebastian Espinosa ◽  
Mahmood S. Hoseini ◽  
Michael P. Stryker
Keyword(s):  
Visual Cortex ◽  
Primary Visual Cortex ◽  
Critical Period ◽  
Visual Experience ◽  
Visual Deprivation ◽  
Monocular Deprivation ◽  
Structural Basis ◽  
Dependent Plasticity ◽  
Anatomical Changes ◽  
Layer 2

AbstractThe developing brain can respond quickly to altered sensory experience by circuit reorganization. During a critical period in early life, neurons in the primary visual cortex rapidly lose responsiveness to an occluded eye and come to respond better to the open eye. While physiological and some of the molecular mechanisms of this process have been characterized, its structural basis, except for the well-known changes in the thalamocortical projection, remains obscure. To elucidate the relationship between synaptic remodeling and functional changes during this experience-dependent process, we used 2-photon microscopy to image synaptic structures of sparsely labeled layer 2/3 neurons in the binocular zone of mouse primary visual cortex. Anatomical changes at presynaptic and postsynaptic sites in mice undergoing monocular visual deprivation (MD) were compared to those in control mice with normal visual experience. We found that postsynaptic spines remodeled quickly in response to MD, with neurons more strongly dominated by the deprived eye losing more spines. These postsynaptic changes parallel changes in visual responses during MD and their recovery after restoration of binocular vision. In control animals with normal visual experience, the formation of presynaptic boutons increased during the critical period and then declined. MD affected bouton formation, but with a delay, blocking it after 3 days. These findings reveal intracortical anatomical changes in cellular layers of the cortex that can account for rapid activity-dependent plasticity.Significance statementThe operation of the cortex depends on the connections among its neurons. Taking advantage of molecular and genetic tools to label major proteins of the presynaptic and postsynaptic densities, we studied how connections of layer 2/3 excitatory neurons in mouse visual cortex were changed by monocular visual deprivation during the critical period, which causes amblyopia. The deprivation induced rapid remodeling of postsynaptic spines and impaired bouton formation. Structural measurement followed by calcium imaging demonstrated a strong correlation between changes in postsynaptic structures and functional responses in individual neurons after monocular deprivation. These findings suggest that anatomical changes at postsynaptic sites serve as a substrate for experience-dependent plasticity in the developing visual cortex.

scholarly journals Supersaturation of VEP in Migraine without Aura Patients Treated with Topiramate: An Anatomo-Functional Biomarker of the Disease

2021 ◽  
Vol 10 (4) ◽  
pp. 769
Author(s):  
Ciro De Luca ◽  
Sara Gori ◽  
Sonia Mazzucchi ◽  
Elisa Dini ◽  
Martina Cafalli ◽  
...  
Keyword(s):  
Visual Cortex ◽  
Cortical Neurons ◽  
Migraine Without Aura ◽  
Inverse Correlation ◽  
Primary Headache ◽  
Contrast Gain ◽  
High Prevalence ◽  
Functional Pathway ◽  
Inhibitory Signaling ◽  
Potential Use

Migraine is a primary headache with high prevalence among the general population, characterized by functional hypersensitivity to both exogenous and endogenous stimuli particularly affecting the nociceptive system. The hyperresponsivity of cortical neurons could be due to a disequilibrium in the excitatory/inhibitory signaling. This study aimed to investigate the anatomo-functional pathway from the retina to the primary visual cortex using visual evoked potentials (VEP). Contrast gain protocol was used in 15 patients diagnosed with migraine without aura (at baseline and after 3 months of topiramate therapy) and 13 controls. A saturation (S) index was assessed to monitor the response of VEP’s amplitude to contrast gain. Non-linear nor monotone growth of VEP (S < 0.95) was defined as supersaturation. A greater percentage of migraine patients (53%) relative to controls (7%) showed this characteristic. A strong inverse correlation was found between the S index and the number of days separating the registration of VEP from the next migraine attack. Moreover, allodynia measured through the Allodynia Symptoms Check-list (ASC-12) correlates with the S index both at baseline and after 3 months of topiramate treatment. Other clinical characteristics were not related to supersaturation. Topiramate therapy, although effective, did not influence electrophysiological parameters suggesting a non-intracortical nor retinal origin of the supersaturation (with possible involvement of relay cells from the lateral geniculate nucleus). In conclusion, the elaboration of visual stimuli and visual cortex activity is different in migraine patients compared to controls. More data are necessary to confirm the potential use of the S index as a biomarker for the migraine cycle (association with the pain-phase) and cortical sensitization (allodynia).

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