Inhibition of Cdk5 in PV Neurons Reactivates Experience-Dependent Plasticity in Adult Visual Cortex

Cyclin-dependent kinase 5 (Cdk5) has been shown to play a critical role in brain development, learning, memory and neural processing in general. Cdk5 is widely distributed in many neuron types in the central nervous system, while its cell-specific role is largely unknown. Our previous study showed that Cdk5 inhibition restored ocular dominance (OD) plasticity in adulthood. In this study, we specifically knocked down Cdk5 in different types of neurons in the visual cortex and examined OD plasticity by optical imaging of intrinsic signals. Downregulation of Cdk5 in parvalbumin-expressing (PV) inhibitory neurons, but not other neurons, reactivated adult mouse visual cortical plasticity. Cdk5 knockdown in PV neurons reduced the evoked firing rate, which was accompanied by an increment in the threshold current for the generation of a single action potential (AP) and hyperpolarization of the resting membrane potential. Moreover, chemogenetic activation of PV neurons in the visual cortex can attenuate the restoration of OD plasticity by Cdk5 inhibition. Taken together, our results suggest that Cdk5 in PV interneurons may play a role in modulating the excitation and inhibition balance to control the plasticity of the visual cortex.

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Contrasting roles for parvalbumin-expressing inhibitory neurons in two forms of adult visual cortical plasticity

eLife ◽

10.7554/elife.11450 ◽

2016 ◽

Vol 5 ◽

Cited By ~ 27

Author(s):

Eitan S Kaplan ◽

Sam F Cooke ◽

Robert W Komorowski ◽

Alexander A Chubykin ◽

Aurore Thomazeau ◽

...

Keyword(s):

Visual Experience ◽

Cortical Plasticity ◽

Ocular Dominance ◽

Critical Role ◽

Monocular Deprivation ◽

Inhibitory Neurons ◽

Similar Increase ◽

Adult Mice ◽

Dependent Modification ◽

Visual Cortical

The roles played by cortical inhibitory neurons in experience-dependent plasticity are not well understood. Here we evaluate the participation of parvalbumin-expressing (PV+) GABAergic neurons in two forms of experience-dependent modification of primary visual cortex (V1) in adult mice: ocular dominance (OD) plasticity resulting from monocular deprivation and stimulus-selective response potentiation (SRP) resulting from enriched visual experience. These two forms of plasticity are triggered by different events but lead to a similar increase in visual cortical response. Both also require the NMDA class of glutamate receptor (NMDAR). However, we find that PV+ inhibitory neurons in V1 play a critical role in the expression of SRP and its behavioral correlate of familiarity recognition, but not in the expression of OD plasticity. Furthermore, NMDARs expressed within PV+ cells, reversibly inhibited by the psychotomimetic drug ketamine, play a critical role in SRP, but not in the induction or expression of adult OD plasticity.

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Optical imaging of the intrinsic signal as a measure of cortical plasticity in the mouse

Visual Neuroscience ◽

10.1017/s0952523805225178 ◽

2005 ◽

Vol 22 (5) ◽

pp. 685-691 ◽

Cited By ~ 83

Author(s):

JIANHUA CANG ◽

VALERY A. KALATSKY ◽

SIEGRID LÖWEL ◽

MICHAEL P. STRYKER

Keyword(s):

Visual Cortex ◽

Optical Imaging ◽

Critical Period ◽

Cortical Plasticity ◽

Ocular Dominance ◽

Screening Method ◽

Intrinsic Signals ◽

Intrinsic Signal ◽

The Mean ◽

Mouse Visual Cortex

The responses of cells in the visual cortex to stimulation of the two eyes changes dramatically following a period of monocular visual deprivation (MD) during a critical period in early life. This phenomenon, referred to as ocular dominance (OD) plasticity, is a widespread model for understanding cortical plasticity. In this study, we designed stimulus patterns and quantification methods to analyze OD in the mouse visual cortex using optical imaging of intrinsic signals. Using periodically drifting bars restricted to the binocular portion of the visual field, we obtained cortical maps for both contralateral (C) and ipsilateral (I) eyes and computed OD maps as (C − I)/(C + I). We defined the OD index (ODI) for individual animals as the mean of the OD map. The ODI obtained from an imaging session of less than 30 min gives reliable measures of OD for both normal and monocularly deprived mice under Nembutal anesthesia. Surprisingly, urethane anesthesia, which yields excellent topographic maps, did not produce consistent OD findings. Normal Nembutal-anesthetized mice have positive ODI (0.22 ± 0.01), confirming a contralateral bias in the binocular zone. For mice monocularly deprived during the critical period, the ODI of the cortex contralateral to the deprived eye shifted negatively towards the nondeprived, ipsilateral eye (ODI after 2-day MD: 0.12 ± 0.02, 4-day: 0.03 ± 0.03, and 6- to 7-day MD: −0.01 ± 0.04). The ODI shift induced by 4-day MD appeared to be near maximal, consistent with previous findings using single-unit recordings. We have thus established optical imaging of intrinsic signals as a fast and reliable screening method to study OD plasticity in the mouse.

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Nerve growth factor (NGF) uptake and transport following injection in the developing rat visual cortex

Visual Neuroscience ◽

10.1017/s095252380000691x ◽

1994 ◽

Vol 11 (6) ◽

pp. 1093-1102 ◽

Cited By ~ 20

Author(s):

Luciano Domenici ◽

Gigliola Fontanesi ◽

Antonio Cattaneo ◽

Paola Bagnoli ◽

Lamberto Maffei

Keyword(s):

Visual Cortex ◽

Nerve Growth Factor ◽

Growth Factor ◽

Critical Period ◽

Cortical Plasticity ◽

Ocular Dominance ◽

Occipital Cortex ◽

Nerve Growth ◽

Visual Cortical ◽

Uptake And Transport

AbstractRecent investigations have shown that cortical nerve growth factor (NGF) infusions during the critical period inhibit ocular-dominance plasticity in the binocular portion of the rat visual cortex. The mechanisms underlying the effects of NGF on visual cortical plasticity are still unclear. To investigate whether during normal development intracortical and/or extracortical cells possess uptake/transport mechanisms for the neurotrophin, we injected 125I-NGF into the occipital cortex of rats at different postnatal ages. Within the cortex, only a few labelled cells were observed. These cells were confined to the vicinity of the injection site and their number depended on the animal's age at the time of injection. Labelled cells were absent at postnatal day (PD) 10 but could be detected between PD 14 and PD 18. They then decreased in number over the following period and were not detected in adult animals. Outside the cortex, neurons of the lateral geniculate nucleus (LGN) were not observed to take up and retrogradely transport NGF at any age after birth. In contrast, retrogradely labelled neurons were found in the basal forebrain. Labelled cells were first observed here at PD 14 and then increased in number until reaching the adult pattern. Our results show that intrinsic and extrinsic neurons are labelled following intracortical injections of iodinated NGF. In both neuronal populations, the uptake and transport of NGF is present over a period corresponding to the critical period for visual cortical plasticity. These findings suggest that NGF may play a role, both intra and extracortically, in plasticity phenomena.

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Transplanted cells are essential for the induction but not the expression of cortical plasticity

10.1101/644377 ◽

2019 ◽

Author(s):

Mahmood S. Hoseini ◽

Benjamin Rakela ◽

Quetzal Flores-Ramirez ◽

Andrea R. Hasenstaub ◽

Arturo Alvarez-Buylla ◽

...

Keyword(s):

Visual Cortex ◽

Critical Period ◽

Cortical Plasticity ◽

Ocular Dominance ◽

Underlying Mechanism ◽

Adult Brain ◽

Inhibitory Neurons ◽

Cortical Responses ◽

Parallel Circuit ◽

Activity Dependent

AbstractTransplantation of even a small number of embryonic inhibitory neurons from the medial ganglionic eminence (MGE) into postnatal visual cortex makes it lose responsiveness to an eye deprived of vision when the transplanted neurons reach the age of the normal critical period of activity-dependent ocular dominance (OD) plasticity. The transplant might induce OD plasticity in the host circuitry or might instead construct a parallel circuit of its own to suppress cortical responses to the deprived-eye. We transplanted MGE neurons expressing archaerhodopsin, closed one eyelid for 4-5 days, and, as expected, observed transplant-induced OD plasticity. This plasticity was evident even when the activity of the transplanted cells was suppressed optogenetically, demonstrating that the plasticity was produced by changes in the host visual cortex.Significance StatementInterneuron transplantation into mouse V1 creates a window of heightened plasticity which is quantitatively and qualitatively similar to the normal critical period, i.e. short-term occlusion of either eye markedly changes ocular dominance. The underlying mechanism of this process is not known. Transplanted interneurons might either form a separate circuit to maintain the ocular dominance shift or might instead trigger changes in the host circuity. We designed experiments to distinguish the two hypotheses. Our findings suggest that while inhibition produced by the transplanted cells triggers this form of plasticity, the host circuity is entirely responsible for maintaining the ocular dominance shift.One Sentence SummaryNeuronal transplants do not just grow and connect—they induce plasticity in the adult brain.

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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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Subanesthetic ketamine reactivates adult cortical plasticity to restore vision from amblyopia

10.1101/2020.03.16.994475 ◽

2020 ◽

Author(s):

Steven F. Grieco ◽

Xin Qiao ◽

Xiaoting Zheng ◽

Yongjun Liu ◽

Lujia Chen ◽

...

Keyword(s):

Functional Recovery ◽

Neural Plasticity ◽

Cortical Plasticity ◽

Brain Plasticity ◽

Excitatory Input ◽

Inhibitory Neurons ◽

List Type ◽

Visual Cortical

SummarySubanesthetic ketamine evokes rapid and long-lasting antidepressant effects in human patients. The mechanism for ketamine’s effects remains elusive, but ketamine may broadly modulate brain plasticity processes. We show that single-dose ketamine reactivates adult mouse visual cortical plasticity and promotes functional recovery of visual acuity defects from amblyopia. Ketamine specifically induces down-regulation of neuregulin-1 (NRG1) expression in parvalbumin-expressing (PV) inhibitory neurons in mouse visual cortex. NRG1 downregulation in PV neurons co-tracks both the fast onset and sustained decreases in synaptic inhibition to excitatory neurons, along with reduced synaptic excitation to PV neurons in vitro and in vivo following a single ketamine treatment. These effects are blocked by exogenous NRG1 as well as PV targeted receptor knockout. Thus ketamine reactivation of adult visual cortical plasticity is mediated through rapid and sustained cortical disinhibition via downregulation of PV-specific NRG1 signaling. Our findings reveal the neural plasticity-based mechanism for ketamine-mediated functional recovery from adult amblyopia.Highlights○ Disinhibition of excitatory cells by ketamine occurs in a fast and sustained manner○ Ketamine evokes NRG1 downregulation and excitatory input loss to PV cells○ Ketamine induced plasticity is blocked by exogenous NRG1 or its receptor knockout○ PV inhibitory cells are the initial functional locus underlying ketamine’s effects

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Critical periods in amblyopia

Visual Neuroscience ◽

10.1017/s0952523817000219 ◽

2018 ◽

Vol 35 ◽

Cited By ~ 47

Author(s):

TAKAO K. HENSCH ◽

ELIZABETH M. QUINLAN

Keyword(s):

Visual Cortex ◽

Critical Period ◽

Molecular Mechanisms ◽

Ocular Dominance ◽

Molecular Genetic ◽

Monocular Deprivation ◽

Critical Periods ◽

Developmental Constraints ◽

Early Postnatal Development ◽

Visual Cortical

AbstractThe shift in ocular dominance (OD) of binocular neurons induced by monocular deprivation is the canonical model of synaptic plasticity confined to a postnatal critical period. Developmental constraints on this plasticity not only lend stability to the mature visual cortical circuitry but also impede the ability to recover from amblyopia beyond an early window. Advances with mouse models utilizing the power of molecular, genetic, and imaging tools are beginning to unravel the circuit, cellular, and molecular mechanisms controlling the onset and closure of the critical periods of plasticity in the primary visual cortex (V1). Emerging evidence suggests that mechanisms enabling plasticity in juveniles are not simply lost with age but rather that plasticity is actively constrained by the developmental up-regulation of molecular ‘brakes’. Lifting these brakes enhances plasticity in the adult visual cortex, and can be harnessed to promote recovery from amblyopia. The reactivation of plasticity by experimental manipulations has revised the idea that robust OD plasticity is limited to early postnatal development. Here, we discuss recent insights into the neurobiology of the initiation and termination of critical periods and how our increasingly mechanistic understanding of these processes can be leveraged toward improved clinical treatment of adult amblyopia.

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Influence of Lateral Connections on the Structure of Cortical Maps

Journal of Neurophysiology ◽

10.1152/jn.00281.2004 ◽

2004 ◽

Vol 92 (5) ◽

pp. 2947-2959 ◽

Cited By ~ 30

Author(s):

Miguel Á. Carreira-Perpiñán ◽

Geoffrey J. Goodhill

Keyword(s):

Visual Cortex ◽

Computational Model ◽

Primary Visual Cortex ◽

Short Range ◽

Ocular Dominance ◽

Characteristic Structure ◽

Interaction Function ◽

Mexican Hat ◽

Visual Cortical ◽

Cortical Map

Maps of ocular dominance and orientation in primary visual cortex have a highly characteristic structure. The factors that determine this structure are still largely unknown. In particular, it is unclear how short-range excitatory and inhibitory connections between nearby neurons influence structure both within and between maps. Using a generalized version of a well-known computational model of visual cortical map development, we show that the number of excitatory and inhibitory oscillations in this interaction function critically influences map structure. Specifically, we demonstrate that functions that oscillate more than once do not produce maps closely resembling those seen biologically. This strongly suggests that local lateral connections in visual cortex oscillate only once and have the form of a Mexican hat.

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Interocular torsional disparity and visual cortical development in the cat

Journal of Neurophysiology ◽

10.1152/jn.1990.64.4.1352 ◽

1990 ◽

Vol 64 (4) ◽

pp. 1352-1360 ◽

Cited By ~ 3

Author(s):

M. R. Isley ◽

D. C. Rogers-Ramachandran ◽

P. G. Shinkman

Keyword(s):

Visual Cortex ◽

Visual Field ◽

Ocular Dominance ◽

Visual Fields ◽

Receptive Fields ◽

Right Visual Field ◽

Orientation Columns ◽

Areas 17 And 18 ◽

The Right ◽

Visual Cortical

1. The present experiments were designed to assess the effects of relatively large optically induced interocular torsional disparities on the developing kitten visual cortex. Kittens were reared with restricted visual experience. Three groups viewed a normal visual environment through goggles fitted with small prisms that introduced torsional disparities between the left and right eyes' visual fields, equal but opposite in the two eyes. Kittens in the +32 degrees goggle rearing condition experienced a 16 degrees counterclockwise rotation of the left visual field and a 16 degrees clockwise rotation of the right visual field; in the -32 degrees goggle condition the rotations were clockwise in the left eye and counterclockwise in the right. In the control (0 degree) goggle condition, the prisms did not rotate the visual fields. Three additional groups viewed high-contrast square-wave gratings through Polaroid filters arranged to provide a constant 32 degrees of interocular orientation disparity. 2. Recordings were made from neurons in visual cortex around the border of areas 17 and 18 in all kittens. Development of cortical ocular dominance columns was severely disrupted in all the experimental (rotated) rearing conditions. Most cells were classified in the extreme ocular dominance categories 1, 2, 6, and 7. Development of the system of orientation columns was also affected: among the relatively few cells with oriented receptive fields in both eyes, the distributions of interocular disparities in preferred stimulus orientation were centered near 0 degree but showed significantly larger variances than in the control condition.(ABSTRACT TRUNCATED AT 250 WORDS)

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Postnatal development of functional properties of visual cortical cells in rats with excitotoxic lesions of basal forebrain cholinergic neurons

Visual Neuroscience ◽

10.1017/s0952523800008816 ◽

1997 ◽

Vol 14 (1) ◽

pp. 111-123 ◽

Cited By ~ 14

Author(s):

Rosita Siciliano ◽

Gigliola Fontanesi ◽

Fiorella Casamenti ◽

Nicoletta Berardi ◽

Paola Bagnoli ◽

...

Keyword(s):

Visual Cortex ◽

Postnatal Development ◽

Functional Properties ◽

Basal Forebrain ◽

Critical Period ◽

Ocular Dominance ◽

Cholinergic Neurons ◽

Field Size ◽

Cortical Cells ◽

Visual Cortical

AbstractIn the rat, visual cortical cells develop their functional properties during a period termed as critical period, which is included between eye opening, i.e.˘postnatal day (PD) 15, and PD40. The present investigation was aimed at studying the influence of cortical cholinergic afferents from the basal forebrain (BF) on the development of functional properties of visual cortical neurons. At PD15, rats were unilaterally deprived of the cholinergic input to the visual cortex by stereotaxic injections of quisqualic acid in BF cholinergic nuclei projecting to the visual cortex. Cortical cell functional properties, such as ocular dominance, orientation selectivity, receptive-field size, and cell responsiveness were then assessed by extracellular recordings in the visual cortex ipsilateral to the lesioned BF both during the critical period (PD30) and after its end (PD45). After the recording session, the rats were sacrificed and the extent of both cholinergic lesion in BF and cholinergic depletion in the visual cortex was determined. Our results show that lesion of BF cholinergic nuclei transiently alters the ocular dominance of visual cortical cells while it does not affect the other functional properties tested. In particular, in lesioned animals recorded during the critical period, a higher percentage of visual cortical cells was driven by the contralateral eye with respect to normal animals. After the end of the critical period, the ocular dominance distribution of animals with cholinergic deafferentation was not significantly different from that of controls. Our results suggest the possibility that lesions of BF cholinergic neurons performed during postnatal development only transiently interfere with cortical competitive processes.

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