Synaptic plasticity is a key mechanism for chronic pain. It occurs at different levels of the central nervous system, including spinal cord and cortex. Studies have mainly focused on signaling proteins that trigger these plastic changes, whereas few have addressed the maintenance of plastic changes related to chronic pain. We found that protein kinase M zeta (PKMζ) maintains pain-induced persistent changes in the mouse anterior cingulate cortex (ACC). Peripheral nerve injury caused activation of PKMζ in the ACC, and inhibiting PKMζ by a selective inhibitor, ζ-pseudosubstrate inhibitory peptide (ZIP), erased synaptic potentiation. Microinjection of ZIP into the ACC blocked behavioral sensitization. These results suggest that PKMζ in the ACC acts to maintain neuropathic pain. PKMζ could thus be a new therapeutic target for treating chronic pain.

Phosphatidylinositol 3-kinase (PI3K) has been implicated in synaptic plasticity and other neural functions in the brain. However, the role of individual PI3K isoforms in the brain is unclear. We investigated the role of PI3Kγ in hippocampal-dependent synaptic plasticity and cognitive functions. We found that PI3Kγ has a crucial and specific role in NMDA receptor (NMDAR)-mediated synaptic plasticity at mouse Schaffer collateral-commissural synapses. Both genetic deletion and pharmacological inhibition of PI3Kγ disrupted NMDAR long-term depression (LTD) while leaving other forms of synaptic plasticity intact. Accompanying this physiological deficit, the impairment of NMDAR LTD by PI3Kγ blockade was specifically correlated with deficits in behavioral flexibility. These findings suggest that a specific PI3K isoform, PI3Kγ, is critical for NMDAR LTD and some forms of cognitive function. Thus, individual isoforms of PI3Ks may have distinct roles in different types of synaptic plasticity and may therefore influence various kinds of behavior.

BackgroundThe Montreal Cognitive Assessment (MoCA) is known to have discriminative power for patients with Mild Cognitive Impairment (MCI). Recently Cognitive Reserve (CR) has been introduced as a factor that compensates cognitive decline. We aimed to assess whether the MoCA reflects CR. Furthermore, we assessed whether there were any differences in the efficacy between the MoCA and the Mini-Mental State Examination (MMSE) in reflecting CR.MethodsMoCA, MMSE, and the Cognitive Reserve Index questionnaire (CRIq) were administered to 221 healthy participants. Normative data and associated factors of the MoCA were identified. Correlation and regression analyses of the MoCA, MMSE and CRIq scores were performed, and the MoCA score was compared with the MMSE score to evaluate the degree to which the MoCA reflected CR.ResultsThe MoCA reflected total CRIq score (CRI; B = 0.076, P < 0.001), CRI-Education (B = 0.066, P <  0.001), and CRI-Working activity (B = 0.025, P = 0.042), while MMSE reflected total CRI (B = 0.044, P <  0.001) and CRI-Education (B = 0.049, P <  0.001) only. The MoCA differed from the MMSE in the reflection of total CRI (Z = 2.30).ConclusionIn this study, we show that the MoCA score reflects CR more sensitively than the MMSE score. Therefore, we suggest that MoCA can be used to assess CR and early cognitive decline.Electronic supplementary materialThe online version of this article (10.1186/s12877-018-0951-8) contains supplementary material, which is available to authorized users.

No abstract

Background: Facial emotion recognition (FER) is impaired in individuals with frontotemporal dementia (FTD) and Alzheimer’s disease (AD) when compared to healthy older adults. Since deficits in emotion recognition are closely related to caregiver burden or social interactions, researchers have fundamental interest in FER performance in patients with dementia.Purpose: The purpose of this study was to identify the performance profiles of six facial emotions (i.e., fear, anger, disgust, sadness, surprise, and happiness) and neutral faces measured among Korean healthy control (HCs), and those with mild cognitive impairment (MCI), AD, and FTD. Additionally, the neuroanatomical correlates of facial emotions were investigated.Methods: A total of 110 (33 HC, 32 MCI, 32 AD, 13 FTD) older adult participants were recruited from two different medical centers in metropolitan areas of South Korea. These individuals underwent an FER test that was used to assess the recognition of emotions or absence of emotion (neutral) in 35 facial stimuli. Repeated measures two-way analyses of variance were used to examine the distinct profiles of emotional recognition among the four groups. We also performed brain imaging and voxel-based morphometry (VBM) on the participants to examine the associations between FER scores and gray matter volume.Results: The mean score of negative emotion recognition (i.e., fear, anger, disgust, and sadness) clearly discriminated FTD participants from individuals with MCI and AD and HC [F(3,106) = 10.829, p < 0.001, η2 = 0.235], whereas the mean score of positive emotion recognition (i.e., surprise and happiness) did not. A VBM analysis showed negative emotions were correlated with gray matter volume of anterior temporal regions, whereas positive emotions were related to gray matter volume of fronto-parietal regions.Conclusion: Impairment of negative FER in patients with FTD is cross-cultural. The discrete neural correlates of FER indicate that emotional recognition processing is a multi-modal system in the brain. Focusing on the negative emotion recognition is a more effective way to discriminate healthy aging, MCI, and AD from FTD in older Korean adults.