Motor training promotes both synaptic and intrinsic plasticity of layer V pyramidal neurons in the primary motor cortex.

Layer V neurons in the primary motor cortex (M1) are important for motor skill learning. Since pretreatment of either CNQX or APV in rat M1 layer V impaired rotor rod learning, we analysed training-induced synaptic plasticity by whole-cell patch-clamp technique in acute brain slices. Rats trained for 1 day showed a decrease in small inhibitory postsynaptic current (mIPSC) frequency and an increase in the paired-pulse ratio of evoked IPSCs, suggesting a transient decrease in presynaptic GABA release in the early phase. Rats trained for 2 days showed an increase in miniature excitatory postsynaptic current (mEPSC) amplitudes/frequency and elevated AMPA/NMDA ratios, suggesting a long-term strengthening of AMPA receptor-mediated excitatory synapses. Importantly, rotor rod performance in trained rats was correlated with the mean mEPSC amplitude and the frequency obtained from that animal. In current-clamp analysis, 1-day-trained rats transiently decreased the current-induced firing rate, while 2-day-trained rats returned to pre-training levels, suggesting dynamic changes in intrinsic properties. Furthermore, western blot analysis of layer V detected decreased phosphorylation of Ser408-409 in GABAA receptor ß3 subunits in 1-day-trained rats, and increased phosphorylation of Ser831 in AMPA receptor GluA1 subunits in 2-day-trained rats. Finally, live-imaging analysis of Thy1-YFP transgenic mice showed that the training rapidly recruited a substantial number of spines for long-term plasticity in M1 layer V neurons. Taken together, these results indicate that motor training induces complex and diverse plasticity in M1 layer V pyramidal neurons. KEY POINTS: Here we examined motor training-induced synaptic and intrinsic plasticity of layer V pyramidal neurons in the primary motor cortex. The training reduced presynaptic GABA release in the early phase, but strengthened AMPA receptor-mediated excitatory synapses in the later phase: acquired motor performance after training correlated with the strength of excitatory synapses rather than inhibitory synapses. As to the intrinsic property, the training transiently decreased the firing rate in the early phase, but returned to pre-training levels in the later phase. Western blot analysis detected decreased phosphorylation of Ser408-409 in GABAA receptor ß3 subunits in the acute phase, and increased phosphorylation of Ser831 in AMPA receptor GluA1 subunits in the later phase. Live-imaging analysis of Thy1-YFP transgenic mice showed rapid and long-term spine plasticity in M1 layer V neurons, suggesting training-induced increases in self-entropy per spine.

The effect of nano hydroxyapatite coating implant surfaces on gene expression and osseointegration.

BACKGROUND: Hierarchical micro-nano structured topography along with surface chemistry modifications of dental implants have been suggested to positively contribute to the osseointegration process. However, the effect of such surface modifications on the molecular response as well as bone formation rate and quality are still unclear, especially in the early healing period. This study aimed to evaluate the effect of coating a double acid etched (DAE) implant surface with nano-sized (20 nm) hydroxyapatite (Nano) with respect to gene expression, histologic parameters, and nanomechanical properties when compared to DAE control at 1 and 2 weeks after implant placement in a rodent femur model. MATERIAL AND METHODS: Expression of bone-related genes was determined by qRT-PCR (Col-I, Runx-2, Osx, Opn, Ocn, Alp). Histomorphometric evaluation of bone-to-implant contact (BIC) and bone area fraction occupancy (BAFO) within implant threads was performed using photomicrographs after histologic processing. Mechanical properties, reduced elastic modulus and hardness, were determined through nanoindentation. RESULTS: At 1 week, the Nano group demonstrated significantly higher expression of Col-I and Ocn compared to the DAE group, indicating upregulation of osteoprogenitor and osteoblast differentiation genes. At 2 weeks, Nano surface further exhibited enhanced gene expression of Col-I and Osx in comparison to the DAE surface, suggesting an increased mineralization of the newly formed bone. Nanoindentation analysis revealed that the Nano group presented no significant difference on the ranks of reduced elastic modulus and hardness compared to DAE for both timepoints. Histomorphometric analysis yielded no significant difference in the percentage of BIC and BAFO between the Nano and DAE surfaces at 1 and 2 weeks. However, Nano implants did present a higher mean value, ~50%, of BIC compared to DAE, ~30%, after 2 weeks in vivo. CONCLUSIONS: While no significant differences were observed in the amount and mechanical properties of newly formed bone, Nano surface positively and significantly increased the expression osteogenic genes compared to DAE surface at early healing periods.

Changes in fears and worries related to COVID-19 during the pandemic among current employees in Japan: a 5-month longitudinal study.

OBJECTIVES: This study investigates and describes the time course of fears and worries about COVID-19 among current employees during this outbreak. STUDY DESIGN: This was a longitudinal study. METHODS: This study was a part of the Employee Cohort Study in Japan. The study comprised 4120 individuals from February 2019. A baseline survey in March 2020, a 2-month follow-up survey in May 2020, and a 5-month follow-up survey in August 2020 were conducted. Questions surveyed respondents' global fear and worry and six items related to COVID-19. A mixed model for repeated measures of an analysis of variance was used. RESULTS: A total of 1421 respondents completed the baseline survey. At 2- and 5-month follow-ups, 1032 and 1181 respondents completed surveys, respectively. Of those, 64 and 33 individuals who were temporarily laid off or on leave were recorded as missing values. Global fear and worry about COVID-19 significantly increased from March to August 2020. Fears of personal or family infection, limiting one's activities and national and local government policies also significantly increased with time. In contrast, fears of lack of knowledge and difficulty of obtaining hygiene products significantly decreased. CONCLUSION: To conduct efficient risk communication during a pandemic, knowing the concerns of the populace, providing correct information and a sufficient supply of products, and setting clear guidelines are essential.

g Factor of the

The gyromagnetic factor of the low-lying E=251.96(9) keV isomeric state of the nucleus ^{99}Zr was measured using the time-dependent perturbed angular distribution technique. This level is assigned a spin and parity of J^{π}=7/2^{+}, with a half-life of T_{1/2}=336(5) ns. The isomer was produced and spin aligned via the abrasion-fission of a ^{238}U primary beam at RIKEN RIBF. A magnetic moment |µ|=2.31(14)µ_{N} was deduced showing that this isomer is not single particle in nature. A comparison of the experimental values with interacting boson-fermion model IBFM-1 results shows that this state is strongly mixed with a main νd_{5/2} composition. Furthermore, it was found that monopole single-particle evolution changes significantly with the appearance of collective modes, likely due to type-II shell evolution.

Role of mitogen-activated protein kinase pathways in migration of gingival epithelial cells in response to stimulation by cigarette smoke condensate and infection by Porphyromonas gingivalis.

BACKGROUND AND OBJECTIVE: Previous studies have shown that cigarette smoke (CS) and periodontal pathogens could alter wound healing responses of gingival epithelial cells. To elucidate molecular mechanisms leading to these epithelial changes, we studied the signaling pathway involved in the modulation of cell migration by CS condensate (CSC) and the infection by a prominent periodontal pathogen, Porphyromonas gingivalis. MATERIAL AND METHODS: Human gingival epithelial cells (Ca9-22) were treated with CSC or vehicle control for 24 h. Activation of mitogen-activated protein kinases (MAPK) in cells with or without infection by P. gingivalis was assessed by polymerase chain reaction array and immunoblotting using phospho-specific antibodies. Cell migration was assessed using in vitro wound closure model, and specific pharmacologic inhibitors of MAPK pathways were used to characterize further the extent of involvement of the MAPK pathways. RESULTS: Polymerase chain reaction array showed that gene expression of several members of the MAPK, particularly p38 and JNK, was upregulated more than twofold in Ca9-22 cells stimulated with 10 µg/mL CSC. Coincubation with P. gingivalis induced a different pattern of gene expression for MAPK pathways, but it did not suppress the MAPK-related genes upregulated by CSC. A significant phosphorylation of ERK1/2 and p38 was observed in cells stimulated with 10 µg/mL CSC (p < 0.05), whereas coincubation with a higher concentration of CSC (250 µg/mL) evoked no such activation. P. gingivalis infection resulted in a tendency to reduce the phosphorylation of ERK1/2 and p38, which had been enhanced by stimulation with 10 µg/mL CSC. Incubation with ERK1/2 and p38 inhibitors significantly reduced the wound closure of CSC-stimulated cells, by approximately 43% and 46%, respectively (p < 0.05). CONCLUSION: CSC exerts effects on the migration of human gingival epithelial cells through the activation of the MAPK ERK1/2 and p38 signaling pathways. P. gingivalis infection attenuates the CSC-induced migration at least partly by suppressing the phosphorylation of ERK1/2 and p38, but other pathways are likely to be involved in this modulatory process.

Does Internet-based cognitive behavioral therapy (iCBT) prevent major depressive episode for workers? A 12-month follow-up of a randomized controlled trial.

BACKGROUND: In this study we investigated whether an Internet-based computerized cognitive behavioral therapy (iCBT) program can decrease the risk of DSM-IV-TR major depressive episodes (MDE) during a 12-month follow-up of a randomized controlled trial of Japanese workers. METHOD: Participants were recruited from one company and three departments of another company. Those participants who did not experience MDE in the past month were randomly allocated to intervention or control groups (n = 381 for each). A 6-week, six-lesson iCBT program was provided to the intervention group. While the control group only received the usual preventive mental health service for the first 6 months, the control group was given a chance to undertake the iCBT program after a 6-month follow-up. The primary outcome was a new onset of DSM-IV-TR MDE during the 12-month follow-up, as assessed by means of the web version of the WHO Composite International Diagnostic Interview (CIDI), version 3.0 depression section. RESULTS: The intervention group had a significantly lower incidence of MDE at the 12-month follow-up than the control group (Log-rank χ2 = 7.04, p < 0.01). The hazard ratio for the intervention group was 0.22 (95% confidence interval 0.06-0.75), when estimated by the Cox proportional hazard model. CONCLUSIONS: The present study demonstrates that an iCBT program is effective in preventing MDE in the working population. However, it should be noted that MDE was measured by self-report, while the CIDI can measure the episodes more strictly following DSM-IV criteria.

Cigarette smoke condensate modulates migration of human gingival epithelial cells and their interactions with Porphyromonas gingivalis.

BACKGROUND AND OBJECTIVE: Epithelial cells are recognized as the first line of defense against bacterial infection and environmental harmful stimuli such as cigarette smoke (CS). Although previous studies explored the effects of nicotine on host cells, mechanisms by which CS affects cellular functions remain uncertain. The present study investigated the effects of CS condensate (CSC) on in vitro wound closure of gingival epithelial cells and their potential interactions with a major periodontal pathogen, Porphyromonas gingivalis. MATERIAL AND METHODS: Human gingival epithelial cells (Ca9-22) were treated with CSC for 24 h. Cell proliferation was determined using a WST-1 assay. Cell migration was assessed using a wound closure model. The expression of integrins was analyzed by confocal scanning laser microscopy and real-time PCR. Intracellular invasion of P. gingivalis was evaluated by confocal scanning laser microscopy and an antibiotic protection assay. RESULTS: Low concentrations (1-10 µg/mL) of CSC showed no significant effect on cell proliferation. CSC demonstrated dual effects on epithelial wound closure of Ca9-22 cells: high concentrations (i.e. 250 µg/mL) significantly inhibited the wound closure whereas low concentrations (i.e. 10 µg/mL) promoted it (p < 0.01). CSC induced distinct changes in cytoskeleton. When CSC-exposed cells were infected with P. gingivalis for 2 h, a significant inhibition of wound closure was observed concurrent with a decrease in integrin α3 expression near the wound area. A significantly increased P. gingivalis invasion into Ca9-22 was observed when exposed to low concentrations of CSC. CONCLUSION: Low concentrations of CSC increased invasion of human gingival epithelial cells by P. gingivalis and induced changes in cytoskeleton and integrin expression, thereby modulating the cell migration.

Demonstration of nuclear gamma-ray polarimetry based on a multi-layer CdTe Compton camera.

To detect and track structural changes in atomic nuclei, the systematic study of nuclear levels with firm spin-parity assignments is important. While linear polarization measurements have been applied to determine the electromagnetic character of gamma-ray transitions, the applicable range is strongly limited due to the low efficiency of the detection system. The multi-layer Cadmium-Telluride (CdTe) Compton camera can be a state-of-the-art gamma-ray polarimeter for nuclear spectroscopy with the high position sensitivity and the detection efficiency. We demonstrated the capability to operate this detector as a reliable gamma-ray polarimeter by using polarized 847-keV gamma rays produced by the [Formula: see text]([Formula: see text]) reaction. By combining the experimental data and simulated calculations, the modulation curve for the gamma ray was successfully obtained. A remarkably high polarization sensitivity was achieved, compatible with a reasonable detection efficiency. Based on the obtained results, a possible future gamma-ray polarimetery is discussed.

First demonstration of MC-EDFA-repeatered SDM transmission of 40 x 128-Gbit/s PDM-QPSK signals per core over 6,160-km 7-core MCF.

We demonstrate the first 7-core multicore erbium-doped fiber amplified (MC-EDFA) transmission of 40 x 128-Gbit/s PDM-QPSK signals over 6,160-km 7-core multicore fiber (MCF). The crosstalk (XT) from all of the other 6 cores of a MC-EDFA and a 55-km length MCF are about -46.5 dB and -45.6 dB at center core, respectively. The core-to-core rotation approach at every amplified span is used to average the XT of all cores. The averaged optical signal-to-noise ratio (OSNR) after 6,160-km transmission is 15.6 dB with 0.1 nm resolution bandwidth. The Q-factor of all 40 channels surpasses the threshold of the forward-error-correction of 6.4 dB with 1 dB margin after 6,160 km. The total net capacity is 28.8 Tbit/s per fiber and achieved capacity-distance product is 177 Pbit/s.km per fiber. We confirmed the feasibility of MC-EDFA repeatered systems for trans-oceanic transmission.

Cerebral blood flow and freezing of gait in Parkinson's disease.

OBJECTIVE: We investigated the relationship between freezing of gait (FOG) severity in Parkinson's disease (PD) and regional cerebral blood flow (rCBF) using single-photon emission computed tomography (SPECT) and evaluated the effect of selegiline therapy. METHOD: We evaluated 54 patients with PD (FOG positive: 21 patients, and FOG negative: 33 patients) with N-isopropyl-p-[I-123] iodoamphetamine ((123) I-IMP) SPECT and the Unified Parkinson's Disease Rating Scale (UPDRS) part III, Mini-Mental State Examination (MMSE), and Beck Depression Inventory. [Correction added on 18 April 2012, after online publication: In the preceding statement, 55 instead of 54 patients with PD were evaluated, and FOG negative consisted of 34 instead of 33 patients] Furthermore, we examined rCBF in FOG-negative patients treated with levodopa with or without selegiline. RESULTS: Z-values of bilateral Brodmann areas (BA) 10 and 11 and left BA32 showed significant increases in the FOG-positive group compared with the FOG-negative group. [Correction added on 18 April 2012, after online publication: In the preceding statement, Z-values was changed to Z-scores] There were significantly positive correlations between Z-values of these areas and FOG score, especially on both sides of BA11. [Correction added on 18 April 2012, after online publication: In the preceding statement, Z-values was changed to Z-scores] An increase in Z-values in bilateral BA10 and 11 and left BA32 in the levodopa-selegiline treatment group after 1 year was significantly inhibited compared with the levodopa treatment group. [Correction added on 18 April 2012, after online publication: In the preceding statement, left BA32 was changed to right BA32, and Z-values was changed to Z-scores] CONCLUSION: There was a close relationship between FOG severity in PD and an increase in rCBF in BA 10, 11 and 32. Furthermore, selegiline's FOG prevention effect may be related to maintaining rCBF in these same areas.

The relationship between depression and regional cerebral blood flow in Parkinson's disease and the effect of selegiline treatment.

OBJECTIVES: We examined the relationship between severity of depression in Parkinson's disease (PD) and regional cerebral blood flow (rCBF) using single photon emission computed tomography (SPECT) and the reaction to levodopa-selegiline combination therapy. MATERIALS AND METHODS: We evaluated 52 patients with PD and nine age-matched controls with SPECT and the Unified Parkinson's Disease Rating Scale (UPDRS) part III, Mini-Mental State Examination (MMSE), and Beck Depression Inventory (BDI) to evaluate depression severity and its connection with rCBF. Furthermore, we examined rCBF in patients with PD treated with levodopa with or without selegiline. RESULTS: A significant fall in rCBF was observed in the bilateral posterior cingulate, hippocampus, and cuneus and the superior parietal and primary visual areas in PD patients with minor depression and in all regions in those with major depression. Elevations in UPDRS part III and BDI scores and falls in MMSE scores were of significantly lower magnitude in the levodopa-selegiline group than in the levodopa group. Whole brain rCBF fell significantly less in the levodopa-selegiline group than in the levodopa group. CONCLUSIONS: These results indicate that selegiline controlled not only worsening of motor function and cognitive function in PD but also aggravation of minor depression, and restrained a fall in whole brain rCBF.

[Tricuspid annuloplasty, pulmonary valve replacement, ventricular septal defect (VSD) patch closure, and right-sided maze procedure 23-years after corrective repair of tetralogy of Fallot].

Postoperative pulmonary valve regurgitation, stenosis of the right ventricular outflow tract, conduit failure, ventricular septal patch leak, secondary tricuspid valve regurgitation, and various arrhythmias are the major complications that develop after surgical repair of tetralogy of Fallot in adults. A 27-year-old male with pulmonary regurgitation, tricuspid regurgitation, residual ventricular septal defect (VSD), low left ventricular function, and chronic atrial fibrillation underwent tricuspid annuloplasty, pulmonary valve replacement with a stentless aortic valve, VSD patch closure, and right-sided maze procedure, and the postoperative course was uneventful. The cardiothoracic ratio decreased, sinus rhythm was restored, and the patient's complaints were relieved. Reoperation at the optimal time after corrective repair of tetralogy of Fallot in adults may improve the outcome.

Executive dysfunction in non-demented Parkinson's disease patients with hallucinations.

OBJECTIVE: We investigated executive function in Parkinson's disease (PD) patients, and focused on executive dysfunction in PD with hallucinations, but without dementia. METHODS: PD patients were classified by cognitive or neuropsychotic status as PD group, PD with vivid dreaming group, PD with hallucinations group and Parkinson's disease dementia (PDD) group. Psychomotor speed tests, the Stroop test, a verbal fluency test and the Self-rating Depression Scale were performed. RESULTS: The PDD group showed poorer scores in every test compared with the PD group. The PD with hallucinations group showed results similar to those of the PDD group, while the PD with vivid dreaming group was similar to the PD group. CONCLUSIONS: The study suggests that PD patients with hallucinations, not extensive enough to qualify as dementia, already have executive dysfunction similar to that seen in PDD patients. Executive dysfunction may be an important substrate for hallucinations even when dementia is not yet apparent.

Assessment of hallucinations in Parkinson's disease using a novel scale.

OBJECTIVE: To assess hallucinations in Parkinson's disease (PD), we developed a novel practical rating scale that evaluates five items including variety, frequency, and severity of hallucinations, caregiver burden levels, and psychiatric status at nighttime. METHODS: Forty-one PD patients and their caregivers were examined regarding the status of the hallucinations associated with PD. RESULTS: As a measure of internal consistency, the Tottori University Hallucination Rating Scale (TUHARS) has a Cronbach's alpha of 0.88. Mini-Mental State Examination (MMSE) and Hoehn-Yahr stage were associated with the TUHARS scores in a multivariate regression analysis. Visual hallucinations are the most common. However, half of the patients who reported visual hallucinations also had other hallucinations. The scale scores in the PD patients with dementia (PDD) group were significantly greater than in the PD patients without dementia (PDnD) group. CONCLUSIONS: TUHARS appears to be a suitable and easily administered instrument for assessment of hallucinations in PD. PD patients experienced various kinds of hallucinations. Hallucinations may have a close relationship with cognitive decline in PD patients.

[Adult Bochdalek hernia with volvulus of the stomach].

We report a rare case of Bochdalek hernia, congenital posterolateral diaphragmatic hernia with volvulus of the stomach, in an adult A 74-year-old man was admitted to our hospital complaining of sudden abdominal pain and vomiting. Roentgenologic examination of the chest showed air above the left diaphragm, and the mediastinum was displaced to the right. Upper gastrointestinal series revealed volvulus of the stomach in which the pylorus was displaced to the left. The surgical repair was done through left thoracotomy with combining laparoscopy and thoracoscopy without surgical complications, 1 year later the patient is asymptomatic.

Work-related psychosocial factors and metabolic syndrome onset among workers: a systematic review and meta-analysis.

BACKGROUND: Work-related psychosocial factors have been associated with metabolic syndrome. However, no systematic reviews or meta-analyses have evaluated this association. METHODS: A systematic literature search was conducted, using PubMed, Embase, PsycINFO, PsycARTICLES and the Japan Medical Abstracts Society. Eligible studies included those that examined the previously mentioned association; had a longitudinal or prospective cohort design; were conducted among workers; provided sufficient data for calculating odds ratios, relative risks or hazard ratios with 95% confidence intervals; were original articles in English or Japanese; and were published no later than 2016. Study characteristics, exposure and outcome variables and association measures of studies were extracted by the investigators independently. RESULTS: Among 4,664 identified studies, 8 were eligible for review and meta-analysis. The pooled risk of adverse work-related stress on metabolic syndrome onset was significant and positive (RR = 1.47; 95% CI, 1.22-1.78). Sensitivity analyses limiting only the effects of job strain and shift work also indicated a significant positive relationship (RR = 1.75; 95% CI, 1.09-2.79; and RR = 1.59; 95% CI, 1.00-2.54, P = 0.049 respectively). CONCLUSION: This study reveals a strong positive association between work-related psychosocial factors and an elevated risk of metabolic syndrome onset. The effects of job strain and shift work on metabolic syndrome appear to be significant.

Transcriptional and posttranscriptional regulation of tumor necrosis factor gene expression in human monocytes.

Regulation of tumor necrosis factor (TNF) gene expression was investigated in resting human monocytes and in 12-O-tetradecanoylphorbol-13-acetate (TPA) activated monocytes. TNF transcripts were undetectable in resting monocytes. However, in TPA-activated monocytes, TNF mRNA was first detectable by 3 h and reached maximal levels by 12 h of drug exposure. Using run-on transcription assays, the TNF gene was transcriptionally inactive in resting monocytes, but was rapidly activated after TPA exposure. The protein synthesis inhibitor, cycloheximide (CHX), had no detectable effect on levels of TNF transcripts in resting monocytes, while this agent superinduced the level of TNF mRNA by 50-fold in TPA-activated cells. TPA activated monocytes were also exposed to actinomycin D and/or CHX to determine whether transcriptional or posttranscriptional control of TNF gene expression was responsible for the induction of TNF transcripts. After 1 h of actinomycin D treatment, the amount of TNF transcripts was reduced by 75%. In contrast, no difference in TNF mRNA levels was observed in TPA-activated monocytes exposed to CHX alone or CHX in combination with actinomycin D. These findings indicated that CHX prevented the degradation of TNF mRNA by inhibiting the synthesis of a labile protein. Run-on transcription assays performed on cells exposed to either TPA or the combination of TPA and CHX further indicated that CHX treatment increased transcription of the TNF gene. Thus, TNF gene expression is controlled at the transcriptional level in resting human monocytes, while both transcriptional and posttranscriptional events regulate the level of TNF transcripts in TPA-activated cells.

Tumor necrosis factor expression in human epithelial tumor cell lines.

Tumor necrosis factor (TNF) is a monokine with in vitro cytotoxicity for some but not all tumor cells. The basis for sensitivity and resistance to the antitumor effects of this agent remains unclear. The present studies have monitored the effects of TNF on 14 epithelial tumor cell lines. Eleven of these cell lines were resistant to the growth inhibitory effects of TNF (50% inhibitory concentration greater than 1,000 U/ml). 12 of the 14 tumor cell lines has detectable levels of high affinity cell surface TNF binding sites, thus suggesting that resistance was not often due to the absence of cell surface TNF receptors. Northern blot analysis demonstrated that three of the eleven resistant cell lines expressed detectable levels of TNF mRNA. Furthermore, both sensitive and resistant epithelial tumor cells had the capacity to express TNF transcripts in the presence of the protein synthesis inhibitor, cycloheximide. Finally, the presence of TNF expression at the RNA level is shown to be associated with the production of a TNF-like protein in the resistant Ov-D ovarian carcinoma cells. These findings suggest that certain human epithelial tumor cell lines inherently resistant to TNF also express this cytokine.

Neural plasticity maintained high by activation of cyclic AMP-dependent protein kinase: an age-independent, general mechanism in cat striate cortex.

Adult cats lack ocular dominance plasticity, showing little change in the ocular dominance distribution following monocular deprivation. Ocular dominance plasticity is also lost in kitten visual cortex that has been continuously infused with either catecholaminergic neurotoxin, beta-adrenoreceptor blocker, or inhibitor of cyclic AMP-dependent protein kinase (protein kinase A). Complementarily, in adult cats we showed earlier that pharmacological activation of protein kinase A, albeit partially, restored ocular dominance plasticity. In the present study, we first asked whether, mediated by protein kinase A activation, the same molecular mechanisms could restore ocular dominance plasticity to kitten cortex that once lost the expression of plasticity due to prior pharmacological treatments. Concurrently with monocular deprivation, two kinds of cyclic AMP-related drugs (cholera toxin A-subunit or dibutyryl cyclic AMP) were directly infused in two types of aplastic kitten cortex pretreated with either 6-hydroxydopamine or propranolol. The combined treatment resulted in clear ocular dominance shift to the non-deprived eye, indicating that cortical plasticity was fully restored to aplastic kitten cortex. Next, to directly prove the sensitivity difference in protein kinase A activation between the immature and mature cortex, we compared the thus-obtained data in kittens with the published data derived from adult cats under the comparable experimental paradigm. The extent of ocular dominance changes following monocular deprivation was compared at different drug concentrations in the two preparations: the shifted ocular dominance distribution in aplastic kitten cortex infused with dibutyryl cyclic AMP at the lowest concentration tested and the W-shaped distribution in similarly treated adult cortex at a thousandfold-higher drug concentration that induced nearly maximal changes. We conclude that, irrespective of the animal's age, activation of protein kinase A cascades is a general mechanism to maintain ocular dominance plasticity high, their sensitivity being substantially higher in the immature than mature cortex.