Synaptic Plasticity In Visual Cortex Research Articles

Effects of enriched environment on the subunits N-mehyl-D-aspartate receptors at the 17th area of the visual cortex in adult amblyopia rats

Objective To explore the effect of enriched environment on the level of NR2A and NR2B subunits of N-mehyl-D-aspartate (NMDA) receptors which belong to glutamate receptors with excitability at the 17th area of the visual cortex in amblyopia rats after the critical period, and to understand the possible mechanism of synaptic plasticity of the visual cortex in adult amblyopia rats. Methods Eighty Wistar rats were divided into normal group and experimental group by random number table.Right eyelids of all rats were sutured through the whole critical period in order to establish monocular deprivation (MD) amblyopia model.The rats in experimental group were divided into the amblyopia group, standard environment (SE) group and environmental enrichment (EE) group on P45 in random.The sutured right eyelids were opened on P46 in the SE group and EE group.All rats were sacrificed to get the 17th area of the left visual cortex on P60, P75 and P105.Three rats were used at different time points from each group.The Ⅰ-Ⅵ layers of the visual cortex area 17 were observed by using hematoxylin-eosin staining.The expression of NMDA-NR2A and NMDA-NR2B was detected by immunohistochemistry.Integrated optical density of NMDA-NR2A and NMDA-NR2B was detected by using special image analysis software (Image-Pro Plus 6.0). The use of animals complied with Regulation on the Managenment Experimental Ainimals from Shandong Eye Institute and Association for Research in Vision and Ophthalmology (ARVO). Results The positive expression of NMDA-NR2A and NMDA-NR2B were observed in the visual cortex.The positive cells were mostly round or elliptical and mainly expressed in cell membrane.The expression of NMDA-NR2A in P60, P75 and P105 from four groups had statistical differences (all at P 0.05). Conclusions The plasticity of visual cortex exists not only in the critical period but also after the critical period of visual development.EE, as a non-invasion method, can improve and recover the synaptic plasticity in visual cortex of adult rats by the expression of NMDA-NR2A and NMDA-NR2B. Key words: Amblyopia; Visual cortex; Synapse; Enriched environment; N-mehyl-D-aspartate receptors

Monocular deprivation delays the dynamic changes of phosphorylated synapsin Ia/b at site-1 in contralateral visual cortex of juvenile mice.

Synapsins as a family of presynaptic terminal phosphoprotein participates in neuronal development, but their role in the synaptic plasticity of visual cortex is unclear. In this study, the impact of monocular deprivation (MD) on dynamic changes of isoform-specific protein expression and site 1 phosphorylation of synapsins in visual cortex of the postnatal mice were observed by using the technique of Western blot analysis. The results showed that the total (T-) protein levels of synapsins including the isoform of Ia/b, IIa/b and IIIa were about 21-26% of adult level in visual cortex of mice at postnatal 7 days (P7), and then the T-synapsin Ia/b and IIb could quickly reach adult level at P35. However, the T-synapsin IIa and IIIa increased more slowly (71-74% at P35), and then kept increasing in the visual cortex of mice at P60. Unlike to the changes of T-synapsins, the level of phosphorylated (P-) synapsin Ia/b (not IIa/b and IIIa) at site 1 increased with development to the highest level at P21, and then decreased rapidly to a low level in visual cortex of mice at P35-60. In addition, we found that the levels of P-synapsin Ia/b increased significantly in left visual cortex of P28 and P35 (not P21 and P42) mice with 1-week MD of right eye; and no significant changes of T-synapsins were observed in both left and right sides of visual cortex in P21-42 mice with MD treatment. These results suggested that the isoform-specific protein expression and site-1 phosphorylation of synapsins might play a different role in the synaptic plasticity of visual cortex, and MD delays the dynamic changes of phosphorylated synapsin Ia/b at site-1 in contralateral visual cortex of juvenile mice.

BACE1 is necessary for experience-dependent homeostatic synaptic plasticity in visual cortex.

Alzheimer's disease (AD) is the most common form of age-related dementia, which is thought to result from overproduction and/or reduced clearance of amyloid-beta (Aβ) peptides. Studies over the past few decades suggest that Aβ is produced in an activity-dependent manner and has physiological relevance to normal brain functions. Similarly, physiological functions for β- and γ-secretases, the two key enzymes that produce Aβ by sequentially processing the amyloid precursor protein (APP), have been discovered over recent years. In particular, activity-dependent production of Aβ has been suggested to play a role in homeostatic regulation of excitatory synaptic function. There is accumulating evidence that activity-dependent immediate early gene Arc is an activity “sensor,” which acts upstream of Aβ production and triggers AMPA receptor endocytosis to homeostatically downregulate the strength of excitatory synaptic transmission. We previously reported that Arc is critical for sensory experience-dependent homeostatic reduction of excitatory synaptic transmission in the superficial layers of visual cortex. Here we demonstrate that mice lacking the major neuronal β-secretase, BACE1, exhibit a similar phenotype: stronger basal excitatory synaptic transmission and failure to adapt to changes in visual experience. Our results indicate that BACE1 plays an essential role in sensory experience-dependent homeostatic synaptic plasticity in the neocortex.

Distinct Sensory Requirements for Unimodal and Cross-Modal Homeostatic Synaptic Plasticity

Loss of a sensory modality elicits both unimodal changes in the deprived cortex and cross-modal alterations in the remaining sensory systems. Unimodal changes are proposed to recruit the deprived cortex for processing the remaining senses, while cross-modal changes are thought to refine processing of spared senses. Hence coordinated unimodal and cross-modal changes are likely beneficial. Despite this expectation, we report in mice that losing behaviorally relevant patterned vision is sufficient to trigger cross-modal synaptic changes in the primary somatosensory cortex barrel fields, but is insufficient to drive unimodal synaptic plasticity in visual cortex (V1), which requires a complete loss of visual activity. In addition, cross-modal changes depend on whisker inputs. Our results demonstrate that unimodal and cross-modal synaptic plasticity occur independently of each other and rely on distinct sensory requirements.

Brain-derived neurotrophic factor (BDNF) reverses the effects of rapid eye movement sleep deprivation (REMSD) on developmentally regulated, long-term potentiation (LTP) in visual cortex slices

Work in this laboratory demonstrated a role for rapid eye movement sleep (REMS) in critical period (CP), postnatal days (P) 17–30, synaptic plasticity in visual cortex. Studies in adolescent rats showed that REMS deprivation (REMSD) reinitiates a developmentally regulated form of synaptic plasticity that otherwise is observed only in CP animals. Subsequent work added that REMSD affects inhibitory mechanisms that are thought to be involved in terminating the CP. Neurotrophins are implicated in the synaptic plasticity that underlies CP maturation and also final closure of the CP in visual cortex. Expression of brain-derived neurotrophic factor (BDNF) is dependent upon neuronal activity, and REMSD may block BDNF expression. We propose that REMS contributes to the maturation of visual cortex through regulation of BDNF expression and consequent, downstream increase in cortical inhibitory tone. In this study, osmotic minipumps delivered BDNF into visual cortex on one side of brain. The opposite hemisphere was not implanted and served as an internal control. We tested the hypothesis that BDNF is blocked by REMSD in late-adolescent rats and investigated whether replacing BDNF prevents induction of LTPWM-III by theta burst stimulation (TBS). We also assessed relative inhibitory tone in visual cortex with paired-pulse stimulation (PPS) in animals that were similarly REMSD- and BDNF-infused. After REMSD, both hemispheres were prepared in parallel for in vitro synaptic plasticity studies (LTPWM-III or PPS). In visual cortex of REMSD rats on the side receiving BDNF infusions (8 of 8 animals), TBS consistently failed to induce LTPWM-III. In contrast, LTPWM-III was obtained (5 of 5 animals) in the matched, non-infused hemisphere, as expected in rats of this age. REMSD animals that were unilaterally infused with saline produced LTPWM-III in both hemispheres. PPS studies in another group of REMSD animals that were unilaterally BDNF-infused displayed age-appropriate inhibition of the second response on the BDNF-infused side (5/5), whereas on the non-infused side facilitation was observed (3/3). Intracortical infusion of BDNF in REMSD adolescent rats appears to restore neurochemical processes necessary for termination of the CP for developmentally regulated synaptic plasticity in visual cortex. The results suggest that REMSD blocks BDNF expression and also maturation of inhibitory processes in adolescent visual cortex. These data support REMS’ function in brain development.

Recovery from chronic monocular deprivation following reactivation of thalamocortical plasticity by dark exposure

Chronic monocular deprivation induces severe amblyopia that is resistant to spontaneous reversal. However, dark exposure initiated in adulthood reactivates synaptic plasticity in the visual cortex and promotes recovery from chronic monocular deprivation in Long Evans rats. Here we show that chronic monocular deprivation induces a significant decrease in the density of dendritic spines on principal neurons throughout the deprived visual cortex. Nevertheless, dark exposure followed by reverse deprivation promotes the recovery of dendritic spine density of neurons in all laminae. Importantly, the ocular dominance of neurons in thalamo-recipient laminae of the cortex, and the amplitude of the thalamocortical visually evoked potential recover following dark exposure and reverse deprivation. Thus, dark exposure reactivates widespread synaptic plasticity in the adult visual cortex, including thalamocortical synapses, during the recovery from chronic monocular deprivation.

Synaptic plasticity in the adult visual cortex is regulated by the metabotropic glutamate receptor, mGLUR5

In the intact adult animal, synaptic plasticity in the visual cortex (VC) is a dynamic and naturalistic phenomenon, the mechanisms of which are not yet fully understood. Given its intrinsic role in hippocampal plasticity, we investigated the eVects of pharmacological antagonism of mGluR5 on synaptic plasticity and receptor expression in the VC of freely moving adult pigmented rats, and compared this with hippocampal effects. Persistent long-term potentiation (LTP, >24 h) in layer II/III of the primary VC, and LTP in the dentate gyrus, were impaired by application of the mGluR5 antagonist 2-methyl-6-(phenylethynyl) pyridine (MPEP). Long-term depression in VC was unaffected. Twenty-four hours after MPEP treatment, mGluR1a monomer expression was reduced in the VC but not in the hippocampus, whereas dimer expression was unaffected; mGluR2/3 and mGluR5 monomers were unaffected, but dimers were reduced in the VC. Our data suggest that mGluR5 is engaged in the regulation of synaptic plasticity in the adult VC and hippocampus: the mechanisms for this may be quite distinct, however. While only LTP is affected by mGluR5-antagonism in the VC, both LTP and LTD are affected in the hippocampus. Furthermore, the higher sensitivity of mGluR expression to antagonism of mGluR5 in VC compared to the hippocampus suggests that mGluR5 regulates plasticity phenomena in these structures by means of distinct mGluR-dependent processes.

Effect of Stochastic Synaptic and Dendritic Dynamics on Synaptic Plasticity in Visual Cortex and Hippocampus

Various forms of synaptic plasticity, including spike timing-dependent plasticity, can be accounted for by calcium-dependent models of synaptic plasticity. However, recent results in which synaptic plasticity is induced by multi-spike protocols cannot simply be accounted for by linear superposition of plasticity due to spike pairs or by existing calcium-dependent models. In this paper, we show that multi-spike protocols can be accounted for if, in addition to the dynamics of back-propagating action potentials, stochastic synaptic dynamics are taken into account. We show that a stochastic implementation can account for the data better than a deterministic implementation and is also more robust. Our results demonstrate that differences between experimental results obtained in hippocampus and visual cortex can be accounted for by the different synaptic and dendritic dynamics in these two systems.

Effect of transgenic overexpression of NR2B on NMDA receptor function and synaptic plasticity in visual cortex

The NMDA receptor (NMDAR) is a heteromer comprised of NR1 and NR2 subunits. Mice that overexpress the NR2B subunit exhibit enhanced hippocampal LTP, prolonged NMDAR currents, and improved memory ( Tang et al., 1999). In the current study, we explored visual cortex plasticity and NMDAR function in NR2B overexpressing transgenic mice. Unlike the hippocampus, in vitro synaptic plasticity of the visual cortex was unaltered by NR2B overexpression. Consistent with the plasticity findings, NMDAR excitatory postsynaptic current (EPSC) durations from layer 2/3 pyramidal cells were similar in wild-type (wt) and transgenic (tg) mice. Furthermore, temporal summation of NMDAR EPSCs to 10, 20, and 40 Hz stimulation did not differ between cells from wt and tg mice. Finally, although in situ studies clearly demonstrate overexpression of NR2B mRNA in visual cortex, we failed to observe a significant elevation in the synaptic expression of NR2B protein. We conclude that the synaptic ratio of NR2B over NR2A in the NMDA receptor complex in the visual cortex is not significantly influenced by the transgene overexpression. These data suggest that mRNA availability is not a limiting factor for the synthesis of NR2B protein in the visual cortex, and support the hypothesis that levels of NR2A, rather than NR2B, normally determine the subunit composition of NMDARs in visual cortex.

The role of N-methyl- d-aspartate receptors in synaptic plasticity of rat visual cortex in vitro: effect of sensory experience

We examined the role of N-methyl- d-aspartate (NMDA) receptors in synaptic plasticity of visual cortex of light (LR) and dark (DR) reared adult rats in vitro. Layer IV stimulation resulted in field potentials in layer II/III, consisting of two excitatory postsynaptic potentials (EPSP) called EPSP1 and EPSP2. Tetanic stimulation induced long-term potentiation (LTP) in EPSP2 of both LR and DR visual cortices. NMDA receptor antagonist d, L-2-amino-5-phosphono-valeric acid (AP5) completely blocked the LTP of EPSP2 in DR visual cortex while it reduced slightly the extent of LTP of EPSP2 in LR ones. Another NMDA receptor antagonist ketamine blocked potentiation of EPSP1 as well as EPSP2 in both groups. Our findings demonstrate that dependency of LTP on NMDA receptors and/or sensitivity of these receptors to the antagonists are different in LR and DR animals.

Effects of the Metabotropic Glutamate Receptor Antagonist MCPG on Phosphoinositide Turnover and Synaptic Plasticity in Visual Cortex

The neurotransmitter glutamate, in addition to activating ligand-gated ion channels, also stimulates phosphoinositide (PI) hydrolysis in neurons by activating a group of G-protein-coupled metabotropic glutamate receptors (mGluRs). A role for mGluRs in synaptic plasticity originally was hypothesized based on the observation that the developmental decline in glutamate-stimulated PI turnover is well correlated with the decline in experience-dependent synaptic plasticity in visual cortex. Over the past few years, the compound alpha-methyl-4-carboxyphenylglycine (MCPG) has been widely used to test the role of PI-coupled mGluRs in a number of types of synaptic plasticity, including long-term potentiation (LTP), long-term depression (LTD), ocular dominance plasticity in visual cortex, and the neural plasticity underlying learning and memory. The conclusions of most of these studies were based on the assumption that MCPG blocks the actions of glutamate at PI-coupled mGluRs in the cerebral cortex. Here we show that this assumption is not valid in visual cortex. Although MCPG does antagonize the actions of the synthetic mGluR agonist 1S, 3R-aminocyclopentane-1,3-dicarboxylic acid, it fails to block PI turnover and changes in spike adaptation stimulated by glutamate, the endogenous mGluR ligand. In addition, we find that MCPG fails to block the NMDA receptor-dependent forms of LTP, LTD, and depotentiation in visual cortex.

Co-regulation of long-term potentiation and experience-dependent synaptic plasticity in visual cortex by age and experience.

Long-term potentiation (LTP) is a lasting enhancement of excitatory synaptic transmission that follows specific patterns of electrical stimulation. Although the mechanism of LTP has been intensively studied, particularly in the hippocampus, its significance for normal brain function remains unproven. It has been proposed that LTP-like mechanisms may contribute to naturally occurring, experience-dependent synaptic modifications in the visual cortex. The formation of normal binocular connections within the visual cortex requires simultaneous input from both eyes during a postnatal critical period that can be delayed by rearing animals in complete darkness. To explore the role of LTP in this experience-dependent maturation process, we induced LTP in visual cortical slices taken at different ages from light-reared and dark-reared rats. Susceptibility to LTP coincides with the critical period and, like the critical period, can be prolonged by rearing animals in darkness. These findings support the hypothesis that LTP reflects a normal mechanism of experience-dependent synaptic modification in the developing mammalian brain.

Synaptic plasticity in visual cortex: comparison of theory with experiment

1. The aim of this work was to assess whether a form of synaptic modification based on the theory of Bienenstock, Cooper, and Munro (BCM) can, with a fixed set of parameters, reproduce both the kinetics and equilibrium states of experience-dependent modifications cortex. 2. According to the BCM theory, the connection strength of excitatory geniculocortical synapses varies as the product of a measure of input activity (d) and a function (phi) of the summed postsynaptic response. For all postsynaptic responses greater than spontaneous but less than a critical value called the "modification threshold" (theta), phi has a negative value. For all postsynaptic responses greater than theta, phi has a positive value. A novel feature of the BCM theory is that the value of theta is not fixed, but rather "slides" as a nonlinear function of the average postsynaptic response. 3. This theory permits precise specification of theoretical equivalents of experimental situations, allowing detailed, quantitative comparisons of theory with experiment. Such comparisons were carried out here in a series of computer simulations. 4. Simulations are performed by presenting input to a model cortical neuron, calculating the summed postsynaptic response, and then changing the synaptic weights according to the BCM theory. This process is repeated until the synaptic weights reach an equilibrium state. 5. Two types of geniculocortical input are simulated: "pattern" and "noise." Pattern input is assumed to correspond to the type of input that arises when a visual contour of a particular orientation is presented to the retina. This type of input is said to be "correlated" when the two sets of geniculocortical fibers relaying information from the two eyes convey the same patterns at the same time. Noise input is assumed to correspond to the type of input that arises in the absence of visual contours and, by definition, is uncorrelated. 6. By varying the types of input available to the two sets of geniculocortical synapses, we simulate the following types of visual experience: 1) normal binocular contour vision, 2) monocular deprivation, 3) reverse suture, 4) strabismus, 5) binocular deprivation, and 6) normal contour vision after a period of monocular deprivation. 7. The constraints placed on the set of parameters by each type of simulated visual environment, and the effects that such constraints have on the evolution of the synaptic weights, are investigated in detail.(ABSTRACT TRUNCATED AT 400 WORDS)