Motility of dendritic spines in visual cortex in vivo: Changes during the critical period and effects of visual deprivation

Layer 6 (L6) of primary sensory cortices is distinct from other layers in that it provides a major cortical input to primary sensory thalamic nuclei. L6 pyramidal neurons in the primary visual cortex (V1) send projections to the lateral geniculate nucleus (LGN), as well as to the thalamic reticular nucleus and higher order thalamic nuclei. Although L6 neurons are proposed to modulate the activity of thalamic relay neurons, how sensory experience regulates L6 neurons is largely unknown. Several days of visual deprivation homeostatically adjusts excitatory synapses in L4 and L2/3 of V1 depending on the developmental age. For instance, L4 exhibits an early critical period during which visual deprivation homeostatically scales up excitatory synaptic transmission. On the other hand, homeostatic changes in L2/3 excitatory synapses are delayed and persist into adulthood. In the present study we examined how visual deprivation affects excitatory synapses on L6 pyramidal neurons. We found that L6 pyramidal neurons homeostatically increase the strength of excitatory synapses following 2 days of dark exposure (DE), which was readily reversed by 1 day of light exposure. This effect was restricted to an early critical period, similar to that reported for L4 neurons. However, at a later developmental age, a longer duration of DE (1 wk) decreased the strength of excitatory synapses, which reversed to normal levels with light exposure. These changes are opposite to what is predicted from the homeostatic plasticity theory. Our results suggest that L6 neurons differentially adjust their excitatory synaptic strength to visual deprivation depending on the age of the animals.

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Gene expression patterns in visual cortex during the critical period: Synaptic stabilization and reversal by visual deprivation

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.0710172105 ◽

2008 ◽

Vol 105 (27) ◽

pp. 9409-9414 ◽

Cited By ~ 41

Author(s):

A. W. Lyckman ◽

S. Horng ◽

C. A. Leamey ◽

D. Tropea ◽

A. Watakabe ◽

...

Keyword(s):

Gene Expression ◽

Visual Cortex ◽

Critical Period ◽

Expression Patterns ◽

Visual Deprivation ◽

Gene Expression Patterns ◽

Synaptic Stabilization

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Arc restores juvenile plasticity in adult mouse visual cortex

10.1101/130880 ◽

2017 ◽

Author(s):

Kyle R. Jenks ◽

Taekeun Kim ◽

Elissa D. Pastuzyn ◽

Hiroyuki Okuno ◽

Andrew V. Taibi ◽

...

Keyword(s):

Visual Cortex ◽

Neural Plasticity ◽

Critical Period ◽

Adult Mouse ◽

Monocular Deprivation ◽

Protein Synthesis Inhibitor ◽

Adult Mice ◽

Mouse Visual Cortex ◽

Activity Dependent

AbstractThe molecular basis for the decline in experience-dependent neural plasticity over age remains poorly understood. In visual cortex, the robust plasticity induced in juvenile mice by brief monocular deprivation (MD) during the critical period is abrogated by genetic deletion of Arc, an activity-dependent regulator of excitatory synaptic modification. Here we report that augmenting Arc expression in adult mice prolongs juvenile-like plasticity in visual cortex, as assessed by recordings of ocular dominance (OD) plasticity in vivo. A distinguishing characteristic of juvenile OD plasticity is the weakening of deprived-eye responses, believed to be accounted for by the mechanisms of homosynaptic long-term depression (LTD). Accordingly, we also found increased LTD in visual cortex of adult mice with augmented Arc expression, and impaired LTD in visual cortex of juvenile mice that lack Arc or have been treated in vivo with a protein synthesis inhibitor. Further, we found that although activity-dependent expression of Arc mRNA does not change with age, expression of Arc protein is maximal during the critical period and declines in adulthood. Finally, we show that acute augmentation of Arc expression in wild type adult mouse visual cortex is sufficient to restore juvenile-like plasticity. Together, our findings suggest a unifying molecular explanation for the age- and activity-dependent modulation of synaptic sensitivity to deprivation.Significance StatementNeuronal plasticity peaks early in life during critical periods and normally declines with age, but the molecular changes that underlie this decline are not fully understood. Using the mouse visual cortex as a model, we found that activity-dependent expression of the neuronal protein Arc peaks early in life, and that loss of activity-dependent Arc expression parallels loss of synaptic plasticity in the visual cortex. Genetic overexpression of Arc prolongs the critical period of visual cortex plasticity and acute viral expression of Arc in adult mice can restore juvenile-like plasticity. These findings provide a mechanism for the loss of excitatory plasticity with age, and suggest that Arc may be an exciting therapeutic target for modulation of the malleability of neuronal circuits.

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Closing the Critical Period Is Required for the Maturation of Binocular Integration in Mouse Primary Visual Cortex

Frontiers in Cellular Neuroscience ◽

10.3389/fncel.2021.749265 ◽

2021 ◽

Vol 15 ◽

Author(s):

Jiangping Chan ◽

Xiangwen Hao ◽

Qiong Liu ◽

Jianhua Cang ◽

Yu Gu

Keyword(s):

Visual Cortex ◽

Mouse Model ◽

Primary Visual Cortex ◽

Depth Perception ◽

Critical Period ◽

Visual Experience ◽

Extracellular Recording ◽

Molecular Assay ◽

Binocular Matching

Binocular matching of orientation preference between the two eyes is a common form of binocular integration that is regarded as the basis for stereopsis. How critical period plasticity enables binocular matching under the guidance of normal visual experience has not been fully demonstrated. To investigate how critical period closure affects the binocular matching, a critical period prolonged mouse model was constructed through the administration of bumetanide, an NKCC1 transporter antagonist. Using acute in vivo extracellular recording and molecular assay, we revealed that binocular matching was transiently disrupted due to heightened plasticity after the normal critical period, together with an increase in the density of spines and synapses, and the upregulation of GluA1 expression. Diazepam (DZ)/[(R, S)-3-(2-carboxypiperazin-4-yl) propyl-1-phosphonic acid (CPP)] could reclose the extended critical period, and rescue the deficits in binocular matching. Furthermore, the extended critical period, alone, with normal visual experience is sufficient for the completion of binocular matching in amblyopic mice. Similarly, prolonging the critical period into adulthood by knocking out Nogo-66 receptor can prevent the normal maturation of binocular matching and depth perception. These results suggest that maintaining an optimal plasticity level during adolescence is most beneficial for the systemic maturation. Extending the critical period provides new clues for the maturation of binocular vision and may have critical implications for the treatment of amblyopia.

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Temporal patterns of fluoxetine-induced plasticity in the mouse visual cortex

10.1101/487553 ◽

2018 ◽

Author(s):

Anna Steinzeig ◽

Cecilia Cannarozzo ◽

Eero Castren

Keyword(s):

Visual Cortex ◽

Critical Period ◽

Ocular Dominance ◽

Temporal Patterns ◽

Monocular Deprivation ◽

Adult Brain ◽

Postnatal Life ◽

Critical Periods ◽

Mouse Visual Cortex

Heightened neuronal plasticity expressed during early postnatal life has been thought to permanently decline once critical periods have ended. For example, monocular deprivation is able to shift ocular dominance in the mouse visual cortex during the first months of life, but this effect is lost later in life. However, various treatments such as the antidepressant fluoxetine can reactivate a critical period-like plasticity in the adult brain. When monocular deprivation is supplemented with chronic fluoxetine administration, a major shift in ocular dominance is produced after the critical period has ended. In the current study, we characterized the temporal patterns of fluoxetine-induced plasticity in the adult mouse visual cortex, using in vivo optical imaging. We found that artificially-induced plasticity in ocular dominance extended beyond the duration of the naturally occurring critical period, and continued as long as fluoxetine was administered. However, this fluoxetine-induced plasticity period ended as soon as the drug was not given. Taken together, our data highlights how a combination of pharmacological treatment and environmental change could be used to improve strategies in antidepressant therapy in humans.

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Arc restores juvenile plasticity in adult mouse visual cortex

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1700866114 ◽

2017 ◽

Vol 114 (34) ◽

pp. 9182-9187 ◽

Cited By ~ 19

Author(s):

Kyle R. Jenks ◽

Taekeun Kim ◽

Elissa D. Pastuzyn ◽

Hiroyuki Okuno ◽

Andrew V. Taibi ◽

...

Keyword(s):

Visual Cortex ◽

Neural Plasticity ◽

Critical Period ◽

Adult Mouse ◽

Monocular Deprivation ◽

Protein Synthesis Inhibitor ◽

Adult Mice ◽

Mouse Visual Cortex ◽

Activity Dependent

The molecular basis for the decline in experience-dependent neural plasticity over age remains poorly understood. In visual cortex, the robust plasticity induced in juvenile mice by brief monocular deprivation during the critical period is abrogated by genetic deletion of Arc, an activity-dependent regulator of excitatory synaptic modification. Here, we report that augmenting Arc expression in adult mice prolongs juvenile-like plasticity in visual cortex, as assessed by recordings of ocular dominance (OD) plasticity in vivo. A distinguishing characteristic of juvenile OD plasticity is the weakening of deprived-eye responses, believed to be accounted for by the mechanisms of homosynaptic long-term depression (LTD). Accordingly, we also found increased LTD in visual cortex of adult mice with augmented Arc expression and impaired LTD in visual cortex of juvenile mice that lack Arc or have been treated in vivo with a protein synthesis inhibitor. Further, we found that although activity-dependent expression of Arc mRNA does not change with age, expression of Arc protein is maximal during the critical period and declines in adulthood. Finally, we show that acute augmentation of Arc expression in wild-type adult mouse visual cortex is sufficient to restore juvenile-like plasticity. Together, our findings suggest a unifying molecular explanation for the age- and activity-dependent modulation of synaptic sensitivity to deprivation.

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

10.1101/743690 ◽

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.

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Myelin densities in retinotopically defined dorsal visual areas of the macaque

Brain Structure and Function ◽

10.1007/s00429-021-02363-z ◽

2021 ◽

Author(s):

Xiaolian Li ◽

Qi Zhu ◽

Wim Vanduffel

Keyword(s):

Visual Cortex ◽

Visual Field ◽

Cortical Thickness ◽

New World Monkeys ◽

Isotropic Resolution ◽

Density Mapping ◽

Area V2 ◽

Visual Areas ◽

Density Results

AbstractThe visuotopic organization of dorsal visual cortex rostral to area V2 in primates has been a longstanding source of controversy. Using sub-millimeter phase-encoded retinotopic fMRI mapping, we recently provided evidence for a surprisingly similar visuotopic organization in dorsal visual cortex of macaques compared to previously published maps in New world monkeys (Zhu and Vanduffel, Proc Natl Acad Sci USA 116:2306–2311, 2019). Although individual quadrant representations could be robustly delineated in that study, their grouping into hemifield representations remains a major challenge. Here, we combined in-vivo high-resolution myelin density mapping based on MR imaging (400 µm isotropic resolution) with fine-grained retinotopic fMRI to quantitatively compare myelin densities across retinotopically defined visual areas in macaques. Complementing previously documented differences in populational receptive-field (pRF) size and visual field signs, myelin densities of both quadrants of the dorsolateral posterior area (DLP) and area V3A are significantly different compared to dorsal and ventral area V3. Moreover, no differences in myelin density were observed between the two matching quadrants belonging to areas DLP, V3A, V1, V2 and V4, respectively. This was not the case, however, for the dorsal and ventral quadrants of area V3, which showed significant differences in MR-defined myelin densities, corroborating evidence of previous myelin staining studies. Interestingly, the pRF sizes and visual field signs of both quadrant representations in V3 are not different. Although myelin density correlates with curvature and anticorrelates with cortical thickness when measured across the entire cortex, exactly as in humans, the myelin density results in the visual areas cannot be explained by variability in cortical thickness and curvature between these areas. The present myelin density results largely support our previous model to group the two quadrants of DLP and V3A, rather than grouping DLP- with V3v into a single area VLP, or V3d with V3A+ into DM.

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Critical periods for functional and anatomical compensation in lateral suprasylvian visual area following removal of visual cortex in cats

Journal of Neurophysiology ◽

10.1152/jn.1984.52.5.941 ◽

1984 ◽

Vol 52 (5) ◽

pp. 941-960 ◽

Cited By ~ 39

Author(s):

L. Tong ◽

R. E. Kalil ◽

P. D. Spear

Keyword(s):

Visual Cortex ◽

Critical Period ◽

Ocular Dominance ◽

Direction Selectivity ◽

Visual Area ◽

Critical Periods ◽

Cortex Lesion ◽

Thalamic Projections ◽

Adult Cats ◽

Visual Cortical

Previous experiments have found that neurons in the cat's lateral suprasylvian (LS) visual area of cortex show functional compensation following removal of visual cortical areas 17, 18, and 19 on the day of birth. Correspondingly, an enhanced retino-thalamic pathway to LS cortex develops in these cats. The present experiments investigated the critical periods for these changes. Unilateral lesions of areas 17, 18, and 19 were made in cats ranging in age from 1 day postnatal to 26 wk. When the cats were adult, single-cell recordings were made from LS cortex ipsilateral to the lesion. In addition, transneuronal autoradiographic methods were used to trace the retino-thalamic projections to LS cortex in many of the same animals. Following lesions in 18- and 26-wk-old cats, there is a marked reduction in direction-selective LS cortex cells and an increase in cells that respond best to stationary flashing stimuli. These results are similar to those following visual cortex lesions in adult cats. In contrast, the percentages of cells with these properties are normal following lesions made from 1 day to 12 wk of age. Thus the critical period for development of direction selectivity and greater responses to moving than to stationary flashing stimuli in LS cortex following a visual cortex lesion ends between 12 and 18 wk of age. Following lesions in 26-wk-old cats, there is a decrease in the percentage of cells that respond to the ipsilateral eye, which is similar to results following visual cortex lesions in adult cats. However, ocular dominance is normal following lesions made from 1 day to 18 wk of age. Thus the critical period for development of responses to the ipsilateral eye following a lesion ends between 18 and 26 wk of age. Following visual cortex lesions in 2-, 4-, or 8-wk-old cats, about 30% of the LS cortex cells display orientation selectivity to elongated slits of light. In contrast, few or no cells display this property in normal adult cats, cats with lesions made on the day of birth, or cats with lesions made at 12 wk of age or later. Thus an anomalous property develops for many LS cells, and the critical period for this property begins later (between 1 day and 2 wk) and ends earlier (between 8 and 12 wk) than those for other properties.(ABSTRACT TRUNCATED AT 400 WORDS)

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