Plasticity In Cortex Research Articles

Low and high dose methamphetamine differentially regulate synaptic structural plasticity in cortex and hippocampus.

Psychostimulants, such as methamphetamine (METH) can induce structural remodeling of synapses by remodeling presynaptic and postsynaptic morphology. Escalating or long-lasting high dose METH accounts for neurodegeneration by targeting multiple neurotransmitters. However, the effects of low dose METH on synaptic structure and the modulation mechanism remain elusive. This study aims to assess the effects of low dose (2 mg/kg) and high dose (10 mg/kg) of METH on synaptic structure alternation in hippocampus and prefrontal cortex (PFC) and to reveal the underlying mechanism involved in the process. Low dose METH promoted spine formation, synaptic number increase, post-synaptic density length elongation, and memory function. High dose of METH induced synaptic degeneration, neuronal number loss and memory impairment. Moreover, high dose, but not low dose, of METH caused gliosis in PFC and hippocampus. Mechanism-wise, low dose METH inactivated ras-related C3 botulinum toxin substrate 1 (Rac1) and activated cell division control protein 42 homolog (Cdc42); whereas high dose METH inactivated Cdc42 and activated Rac1. We provided evidence that low and high doses of METH differentially regulate synaptic plasticity in cortex and hippocampus.

Occlusion of dopamine-dependent synaptic plasticity in the prefrontal cortex mediates the expression of depressive-like behavior and is modulated by ketamine

Unpredictable chronic mild stress (CMS) is among the most popular protocols used to induce depressive-like behaviors such as anhedonia in rats. Differences in CMS protocols often result in variable degree of vulnerability, and the mechanisms behind stress resilience are of great interest in neuroscience due to their involvement in the development of psychiatric disorders, including major depressive disorder. Expression of depressive-like behaviors is likely driven by long-term alterations in the corticolimbic system and by downregulation of dopamine (DA) signaling. Although we have a deep knowledge about the dynamics of tonic and phasic DA release in encoding incentive salience and in response to acute/chronic stress, its modulatory action on cortical synaptic plasticity and the following implications on animal behavior remain elusive. Here, we show that the expression of DA-dependent synaptic plasticity in the medial prefrontal cortex (mPFC) is occluded in rats vulnerable to CMS, likely reflecting differential expression of AMPA receptors. Interestingly, such difference is not observed when rats are acutely treated with sub-anesthetic ketamine, possibly through the recruitment of dopaminergic nuclei such as the ventral tegmental area. In addition, by applying the synaptic activity sensor SynaptoZip in vivo, we found that chronic stress unbalances the synaptic drive from the infralimbic and prelimbic subregions of the mPFC toward the basolateral amygdala, and that this effect is counteracted by ketamine. Our results provide novel insights into the neurophysiological mechanisms behind the expression of vulnerability to stress, as well as behind the antidepressant action of ketamine.

Opposing actions of CRF-R1 and CB1 receptor on facial stimulation-induced MLI-PC plasticity in mouse cerebellar cortex

BackgroundCorticotropin-releasing factor (CRF) is the major neuromodulator orchestrating the stress response, and is secreted by neurons in various regions of the brain. Cerebellar CRF is released by afferents from inferior olivary neurons and other brainstem nuclei in response to stressful challenges, and contributes to modulation of synaptic plasticity and motor learning behavior via its receptors. We recently found that CRF modulates facial stimulation-evoked molecular layer interneuron-Purkinje cell (MLI-PC) synaptic transmission via CRF type 1 receptor (CRF-R1) in vivo in mice, suggesting that CRF modulates sensory stimulation-evoked MLI-PC synaptic plasticity. However, the mechanism of how CRF modulates MLI-PC synaptic plasticity is unclear. We investigated the effect of CRF on facial stimulation-evoked MLI-PC long-term depression (LTD) in urethane-anesthetized mice by cell-attached recording technique and pharmacological methods.ResultsFacial stimulation at 1 Hz induced LTD of MLI-PC synaptic transmission under control conditions, but not in the presence of CRF (100 nM). The CRF-abolished MLI-PC LTD was restored by application of a selective CRF-R1 antagonist, BMS-763,534 (200 nM), but it was not restored by application of a selective CRF-R2 antagonist, antisauvagine-30 (200 nM). Blocking cannabinoid type 1 (CB1) receptor abolished the facial stimulation-induced MLI-PC LTD, and revealed a CRF-triggered MLI-PC long-term potentiation (LTP) via CRF-R1. Notably, either inhibition of protein kinase C (PKC) with chelerythrine (5 µM) or depletion of intracellular Ca2+ with cyclopiazonic acid (100 µM), completely prevented CRF-triggered MLI-PC LTP in mouse cerebellar cortex in vivo.ConclusionsThe present results indicated that CRF blocked sensory stimulation-induced opioid-dependent MLI-PC LTD by triggering MLI-PC LTP through CRF-R1/PKC and intracellular Ca2+ signaling pathway in mouse cerebellar cortex. These results suggest that activation of CRF-R1 opposes opioid-mediated cerebellar MLI-PC plasticity in vivo in mice.

Facial Stimulation Induces Long-Term Potentiation of Mossy Fiber-Granule Cell Synaptic Transmission via GluN2A-Containing N-Methyl-D-Aspartate Receptor/Nitric Oxide Cascade in the Mouse Cerebellum.

Long-term synaptic plasticity in the cerebellar cortex is a possible mechanism for motor learning. Previous studies have demonstrated the induction of mossy fiber-granule cell (MF-GrC) synaptic plasticity under in vitro and in vivo conditions, but the mechanisms underlying sensory stimulation-evoked long-term synaptic plasticity of MF-GrC in living animals are unclear. In this study, we investigated the mechanism of long-term potentiation (LTP) of MF-GrC synaptic transmission in the cerebellum induced by train of facial stimulation at 20 Hz in urethane-anesthetized mice using electrophysiological recording, immunohistochemistry techniques, and pharmacological methods. Blockade of GABAA receptor activity and repetitive facial stimulation at 20 Hz (240 pulses) induced an LTP of MF-GrC synapses in the mouse cerebellar cortical folium Crus II, accompanied with a decrease in paired-pulse ratio (N2/N1). The facial stimulation-induced MF-GrC LTP was abolished by either an N-methyl-D-aspartate (NMDA) receptor blocker, i.e., D-APV, or a specific GluNR2A subunit-containing NMDA receptor antagonist, PEAQX, but was not prevented by selective GluNR2B or GluNR2C/D subunit-containing NMDA receptor blockers. Application of GNE-0723, a selective and brain-penetrant-positive allosteric modulator of GluN2A subunit-containing NMDA receptors, produced an LTP of N1, accompanied with a decrease in N2/N1 ratio, and occluded the 20-Hz facial stimulation-induced MF-GrC LTP. Inhibition of nitric oxide synthesis (NOS) prevented the facial stimulation-induced MF-GrC LTP, while activation of NOS produced an LTP of N1, with a decrease in N2/N1 ratio, and occluded the 20-Hz facial stimulation-induced MF-GrC LTP. In addition, GluN2A-containing NMDA receptor immunoreactivity was observed in the mouse cerebellar granular layer. These results indicate that facial stimulation at 20 Hz induced LTP of MF-GrC synaptic transmission via the GluN2A-containing NMDA receptor/nitric oxide cascade in mice. The results suggest that the sensory stimulation-evoked LTP of MF-GrC synaptic transmission in the granular layer may play a critical role in cerebellar adaptation to native mossy fiber excitatory inputs and motor learning behavior in living animals.

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.

Age-related changes in motor cortex plasticity assessed with non-invasive brain stimulation: an update and new perspectives.

It is commonly accepted that the brains capacity to change, known as plasticity, declines into old age. Recent studies have used a variety of non-invasive brain stimulation (NIBS) techniques to examine this age-related decline in plasticity in the primary motor cortex (M1), but the effects seem inconsistent and difficult to unravel. The purpose of this review is to provide an update on studies that have used different NIBS techniques to assess M1 plasticity with advancing age and offer some new perspective on NIBS strategies to boost plasticity in the ageing brain. We find that early studies show clear differences in M1 plasticity between young and older adults, but many recent studies with motor training show no decline in use-dependent M1 plasticity with age. For NIBS-induced plasticity in M1, some protocols show more convincing differences with advancing age than others. Therefore, our view from the NIBS literature is that it should not be automatically assumed that M1 plasticity declines with age. Instead, the effects of age are likely to depend on how M1 plasticity is measured, and the characteristics of the elderly population tested. We also suggest that NIBS performed concurrently with motor training is likely to be most effective at producing improvements in M1 plasticity and motor skill learning in older adults. Proposed NIBS techniques for future studies include combining multiple NIBS protocols in a co-stimulation approach, or NIBS strategies to modulate intracortical inhibitory mechanisms, in an effort to more effectively boost M1 plasticity and improve motor skill learning in older adults.

Barrel cortex plasticity after photothrombotic stroke involves potentiating responses of pre-existing circuits but not functional remapping to new circuits

Recovery after stroke is thought to be mediated by adaptive circuit plasticity, whereby surviving neurons assume the roles of those that died. However, definitive longitudinal evidence of neurons changing their response selectivity after stroke is lacking. We sought to directly test whether such functional “remapping” occurs within mouse primary somatosensory cortex after a stroke that destroys the C1 barrel. Using in vivo calcium imaging to longitudinally record sensory-evoked activity under light anesthesia, we did not find any increase in the number of C1 whisker-responsive neurons in the adjacent, spared D3 barrel after stroke. To promote plasticity after stroke, we also plucked all whiskers except C1 (forced use therapy). This led to an increase in the reliability of sensory-evoked responses in C1 whisker-responsive neurons but did not increase the number of C1 whisker-responsive neurons in spared surround barrels over baseline levels. Our results argue against remapping of functionality after barrel cortex stroke, but support a circuit-based mechanism for how rehabilitation may improve recovery.

Spinal cord compression is associated with brain plasticity in degenerative cervical myelopathy.

The impact of spinal cord compression severity on brain plasticity and prognostic determinates is not yet fully understood. We investigated the association between the severity of spinal cord compression in patients with degenerative cervical myelopathy, a progressive disease of the spine, and functional plasticity in the motor cortex and subcortical areas using functional magnetic resonance imaging. A 3.0 T MRI scanner was used to acquire functional images of the brain in 23 degenerative cervical myelopathy patients. Patients were instructed to perform a structured finger-tapping task to activate the motor cortex to assess the extent of cortical activation. T2-weighted images of the brain and spine were also acquired to quantify the severity of spinal cord compression. The observed blood oxygen level-dependent signal increase in the contralateral primary motor cortex was associated with spinal cord compression severity when patients tapped with their left hand (r = 0.49, P = 0.02) and right hand (r = 0.56, P = 0.005). The volume of activation in the contralateral primary motor cortex also increased with spinal cord compression severity when patients tapped with their left hand (r = 0.55, P = 0.006) and right hand (r = 0.45, P = 0.03). The subcortical areas (cerebellum, putamen, caudate and thalamus) also demonstrated a significant relationship with compression severity. It was concluded that degenerative cervical myelopathy patients with severe spinal cord compression recruit larger regions of the motor cortex to perform finger-tapping tasks, which suggests that this adaptation is a compensatory response to neurological injury and tissue damage in the spinal cord.

Bypassing use-dependent plasticity in the primary motor cortex to preserve adaptive behavior

Behavioral adaptation, a central feature of voluntary movement, is known to rely on top-down cognitive control. For example, the conflict-adaptation effect on tasks such as the Stroop task leads to better performance (e.g. shorter reaction time) for incongruent trials following an already incongruent one. The role of higher-order cortices in such between-trial adjustments is well documented, however, a specific involvement of the primary motor cortex (M1) has seldom been questioned. Here we studied changes in corticospinal excitability associated with the conflict-adaptation process. For this, we used single-pulse transcranial-magnetic stimulation (TMS) applied between two consecutive trials in an interference flanker task, while measuring motor-evoked potentials (MEPs) after agonistic and antagonistic voluntary movements. In agonist movement, MEP amplitude was modulated by recent movement history with an increase favoring movement repetition, but no significant change in MEP size was observed whether a previous trial was incongruent or congruent. Critically, for an antagonist movement, the relative size of MEPs following incongruent trials correlated positively with the strength of behavioral adaptation measured as the degree of RT shortening across subjects. This post-conflict increase in corticospinal excitability related to antagonist muscle recruitment could compensate for a potential deleterious bias due to recent movement history that favors the last executed action. Namely, it prepares the motor system to rapidly adapt to a changing and unpredictable context by equalizing the preparation for all possible motor responses.

NMDA GluN2C/2D receptors contribute to synaptic regulation and plasticity in the anterior cingulate cortex of adult mice

IntroductionN-Methyl-D-aspartate receptors (NMDARs) play a critical role in different forms of plasticity in the central nervous system. NMDARs are always assembled in tetrameric form, in which two GluN1 subunits and two GluN2 and/or GluN3 subunits combine together. Previous studies focused mainly on the hippocampus. The anterior cingulate cortex (ACC) is a key cortical region for sensory and emotional functions. NMDAR GluN2A and GluN2B subunits have been previously investigated, however much less is known about the GluN2C/2D subunits.ResultsIn the present study, we found that the GluN2C/2D subunits are expressed in the pyramidal cells of ACC of adult mice. Application of a selective antagonist of GluN2C/2D, (2R*,3S*)-1-(9-bromophenanthrene-3-carbonyl) piperazine-2,3-dicarboxylic acid (UBP145), significantly reduced NMDAR-mediated currents, while synaptically evoked EPSCs were not affected. UBP145 affected neither the postsynaptic long-term potentiation (post-LTP) nor the presynaptic LTP (pre-LTP). Furthermore, the long-term depression (LTD) was also not affected by UBP145. Finally, both UBP145 decreased the frequency of the miniature EPSCs (mEPSCs) while the amplitude remained intact, suggesting that the GluN2C/2D may be involved in presynaptic regulation of spontaneous glutamate release.ConclusionsOur results provide direct evidence that the GluN2C/2D contributes to evoked NMDAR mediated currents and mEPSCs in the ACC, which may have significant physiological implications.

Deficits in higher visual area representations in a mouse model of Angelman syndrome

BackgroundSensory processing deficits are common in individuals with neurodevelopmental disorders. One hypothesis is that deficits may be more detectable in downstream, “higher” sensory areas. A mouse model of Angelman syndrome (AS), which lacks expression of the maternally inherited Ube3a allele, has deficits in synaptic function and experience-dependent plasticity in the primary visual cortex. Thus, we hypothesized that AS model mice have deficits in visually driven neuronal responsiveness in downstream higher visual areas (HVAs).MethodsHere, we used intrinsic signal optical imaging and two-photon calcium imaging to map visually evoked neuronal activity in the primary visual cortex and HVAs in response to an array of stimuli.ResultsWe found a highly specific deficit in HVAs. Drifting gratings that changed speed caused a strong response in HVAs in wildtype mice, but this was not observed in littermate AS model mice. Further investigation with two-photon calcium imaging revealed the effect to be largely driven by aberrant responses of inhibitory interneurons, suggesting a cellular basis for higher level, stimulus-selective cortical dysfunction in AS.ConclusionAssaying downstream, or “higher” circuitry may provide a more sensitive measure for circuit dysfunction in mouse models of neurodevelopmental disorders.Trial registrationNot applicable.

The effect of breaking up prolonged sitting on paired associative stimulation-induced plasticity

Paired associative stimulation (PAS) can induce plasticity in the motor cortex, as measured by changes in corticospinal excitability (CSE). This effect is attenuated in older and less active individuals. Although a single bout of exercise enhances PAS-induced plasticity in young, physically inactive adults, it is not yet known if physical activity interventions affect PAS-induced neuroplasticity in middle-aged inactive individuals. Sixteen inactive middle-aged office workers participated in a randomized cross-over design investigating how CSE and short-interval intracortical inhibition (SICI) were affected by PAS preceded by 3 h of sitting (SIT), 3 h of sitting interrupted every 30 min by 3 min of frequent short bouts of physical activity (FPA) and 2.5 h of sitting followed by 25 min of moderate-intensity exercise (EXE). Transcranial magnetic stimulation was applied over the primary motor cortex (M1) of the dominant abductor pollicis brevis to induce recruitment curves before and 5 min and 30 min post-PAS. Linear mixed models were used to compare changes in CSE using time and condition as fixed effects and subjects as random effects. There was a main effect of time on CSE and planned within-condition comparisons showed that CSE was significantly increased from baseline to 5 min and 30 min post-PAS, in the FPA condition, with no significant changes in the SIT or EXE conditions. SICI decreased from baseline to 5 min post-PAS, but this was not related to changes in CSE. Our findings suggest that in middle-aged inactive adults, FPAs may promote corticospinal neuroplasticity. Possible mechanisms are discussed.

CB1 cannabinoid receptor-mediated plasticity of GABAergic synapses in the mouse insular cortex

The insular cortex plays pivotal roles in taste learning. As cellular mechanisms of taste learning, long-term potentiation (LTP) at glutamatergic synapses is well studied. However, little is known about long-term changes of synaptic efficacy at GABAergic synapses in the insular cortex. Here, we examined the synaptic mechanisms of long-term plasticity at GABAergic synapses in layer V pyramidal neurons of the mouse insular cortex. In response to a prolonged high-frequency stimulation (HFS), GABAergic synapses displayed endocannabinod (eCB)-mediated long-term depression (LTDGABA). When cannabinoid 1 receptors (CB1Rs) were blocked by a CB1R antagonist, the same stimuli caused LTP at GABAergic synapses (LTPGABA) which was mediated by production of nitric oxide (NO) via activation of NMDA receptors. Intriguingly, NO signaling was necessary for the induction of LTDGABA. In the presence of leptin which blocks CB1 signaling, the prolonged HFS caused LTPGABA which was mediated by NO signaling. These results indicate that long-term plasticity at GABAergic synapses in the insular cortex can be modulated by combined effects of eCB and NO signaling. These forms of GABAergic synaptic plasticity in the insular cortex may be crucial synaptic mechanisms in taste learning.

Angiotensin II induces coordinated calcium bursts in aldosterone-producing adrenal rosettes

Aldosterone-producing zona glomerulosa (zG) cells of the adrenal gland arrange in distinct multi-cellular rosettes that provide a structural framework for adrenal cortex morphogenesis and plasticity. Whether this cyto-architecture also plays functional roles in signaling remains unexplored. To determine if structure informs function, we generated mice with zG-specific expression of GCaMP3 and imaged zG cells within their native rosette structure. Here we demonstrate that within the rosette, angiotensin II evokes periodic Cav3-dependent calcium events that form bursts that are stereotypic in form. Our data reveal a critical role for angiotensin II in regulating burst occurrence, and a multifunctional role for the rosette structure in activity-prolongation and coordination. Combined our data define the calcium burst as the fundamental unit of zG layer activity evoked by angiotensin II and highlight a novel role for the rosette as a facilitator of cell communication.

Sex difference in synaptic plasticity in the anterior cingulate cortex of adult mice

Sex differences in certain types of pain sensitivity and emotional responses have been previously reported. Synaptic plasticity is a key cellular mechanism for pain perception and emotional regulation, including long-term potentiation (LTP) and long-term depression (LTD). However, it is unclear whether there is a sex difference at synaptic level. Recent studies indicate that excitatory transmission and plasticity in the anterior cingulate cortex (ACC) are critical in chronic pain and pain related emotional responses. In the present study, we used 64-channel multielectrode (MED64) system to record synaptic plasticity in the ACC of male and female adult mice. We found that there was no significant difference in theta-burst stimulation (TBS)-induced LTP between female and male mice. Furthermore, the recruitment of inactive channels was also not different. For LTD, we found that LTD was greater in slices of ACC in male mice than female mice. Our results demonstrate that LTP in the ACC does not show any sex-related difference.

Microglial mechanisms of experience-dependent plasticity in the mouse visual cortex

Microglial mechanisms of experience-dependent plasticity in the mouse visual cortex

Optogenetic stimulation of the VTA modulates a frequency-specific gain of thalamocortical inputs in infragranular layers of the auditory cortex

Reward associations during auditory learning induce cortical plasticity in the primary auditory cortex. A prominent source of such influence is the ventral tegmental area (VTA), which conveys a dopaminergic teaching signal to the primary auditory cortex. Yet, it is unknown, how the VTA influences cortical frequency processing and spectral integration. Therefore, we investigated the temporal effects of direct optogenetic stimulation of the VTA onto spectral integration in the auditory cortex on a synaptic circuit level by current-source-density analysis in anesthetized Mongolian gerbils. While auditory lemniscal input predominantly terminates in the granular input layers III/IV, we found that VTA-mediated modulation of spectral processing is relayed by a different circuit, namely enhanced thalamic inputs to the infragranular layers Vb/VIa. Activation of this circuit yields a frequency-specific gain amplification of local sensory input and enhances corticocortical information transfer, especially in supragranular layers I/II. This effects persisted over more than 30 minutes after VTA stimulation. Altogether, we demonstrate that the VTA exhibits a long-lasting influence on sensory cortical processing via infragranular layers transcending the signaling of a mere reward-prediction error. We thereby demonstrate a cellular and circuit substrate for the influence of reinforcement-evaluating brain systems on sensory processing in the auditory cortex.

17\u03b1 Estradiol promotes plasticity of spared inputs in the adult amblyopic visual cortex

The promotion of structural and functional plasticity by estrogens is a promising approach to enhance central nervous system function in the aged. However, how the sensitivity to estrogens is regulated across brain regions, age and experience is poorly understood. To ask if estradiol treatment impacts structural and functional plasticity in sensory cortices, we examined the acute effect of 17α-Estradiol in adult Long Evans rats following chronic monocular deprivation, a manipulation that reduces the strength and selectivity of deprived eye vision. Chronic monocular deprivation decreased thalamic input from the deprived eye to the binocular visual cortex and accelerated short-term depression of the deprived eye pathway, but did not change the density of excitatory synapses in primary visual cortex. Importantly, we found that the classical estrogen receptors ERα and ERβ were robustly expressed in the adult visual cortex, and that a single dose of 17α-Estradiol reduced the expression of the calcium-binding protein parvalbumin, decreased the integrity of the extracellular matrix and increased the size of excitatory postsynaptic densities. Furthermore, 17α-Estradiol enhanced experience-dependent plasticity in the amblyopic visual cortex, by promoting response potentiation of the pathway served by the non-deprived eye. The promotion of plasticity at synapses serving the non-deprived eye may reflect selectivity for synapses with an initially low probability of neurotransmitter release, and may inform strategies to remap spared inputs around a scotoma or a cortical infarct.

Effects of endurance exercise on synaptic plasticity in cerebral cortex of aged rats and related regulatory mechanism

To understand and analyze the rules of endurance exercise on the cerebral cortex adaptive mechanism in aged rats. In this study, 3-month-old (n=20), 13-month-old (n=24) and 23-month-old (n=24) specific-pathogen free (SPF) male Sprague-Dawley Rat (SD) rats were divided into young (Y-SED), middle-aged (M-SED) and old-aged (O-SED) sedentary control group, and the corresponding Y-EX, M-EX and O-EX in the endurance exercise runner group. The 10-weeks of regular moderate-intensity aerobic exercise intervention were carried out in the endurance exercise runner group. The exercise mode is treadmill exercise (slope 0), and the exercise intensity gradually increases from 60%～65% of the maximum oxygen consumption (V·O2max) to 70%～75%, and the exercise time is 10 weeks. Hematoxylin and eosin (HE) staining was used to detect age-related morphological changes. The expressions of superoxide dismutase(SOD) and brain-derived neurotrophic factor (BDNF) and the expressions of synapsin 1 (SYN1) and Ca2+/calmodulin- dependent protein kinases IIα (CaMK IIα) / AMP-activated protein kinase α1(AMPKα1) / mammalian target of rapamycin (mTOR) pathway -related genes were detected. The cerebral cortex structure of the rats in each group showed age-related aging changes, the expression of SOD in the cortex showed a gradual decline, the expression of BDNF showed an age-increasing trend, and the expression levels of SYN1 and CaMK IIα were increased with age. The changes in AMPKα1 and SirT2 and IP3R, AKT1 and mTOR mRNA levels were increased slightly in middle-aged rats and decreased in aged rats. Compared with the rats in each sedentary control group, the nucleus of the cerebral cortex was tightly arranged and the number of nuclei observed under the microscope was increased significantly in each exercise group. Exercise promoted the expressions of SOD, BDNF and synaptophysin SYN1 in the cortex of rats, and the expression levels of SOD and BDNF in aged rats were up-regulated significantly (P＜ 0.01). The expression level of SYN1 in rats was up-regulated significantly (P＜0.05) in the young and aged rats. The expression of CaMK IIα in the cortex of middle-aged and aged rats was up-regulated (P＜0.01), while the expression level of CaMK IIα in young rats was down-regulated (P＜0.01). Exercise could up-regulate the expression level of AMPKα1 in the cortex of young rats (P＜ 0.05), but not in middle-aged and old-age rats. Exercise could up-regulate the expression of SirT2 in the cortex of rats in all age groups (P＜0.05). Exercise up-regulated the expression of phosphoinositide 3-kinase (IP3R)/ protein kinase B 1(AKT1) /mTOR in the cortex of rats, among which young IP3R was significantly up-regulated (P＜0.01) in the young group, mTOR was significantly up-regulated in young and middle-aged group (P＜0.01), and mTOR was also significantly up-regulated in the aged group (P＜0.05). Endurance exercise up-regulates BDNF expression, regulates CaMKIIα signaling, activates AMPK signaling pathway and IP3R / AKT1 / mTOR signaling pathway, and improves synaptic plasticity in the cortex.

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