Neural processing of high and low spatial frequency information in faces changes across development: qualitative changes in face processing during adolescence

Face perception in adults depends on skilled processing of interattribute distances (‘configural’ processing), which is disrupted for faces presented in inverted orientation (face inversion effect or FIE). Children are not proficient in configural processing, and this might relate to an underlying immaturity to use facial information in low spatial frequency (SF) ranges, which capture the coarse information needed for configural processing. We hypothesized that during adolescence a shift from use of high to low SF information takes place. Therefore, we studied the influence of SF content on neural face processing in groups of children (9–10 years), adolescents (14–15 years) and young adults (21–29 years) by measuring event‐related potentials (ERPs) to upright and inverted faces which varied in SF content. Results revealed that children show a neural FIE in early processing stages (i.e. P1; generated in early visual areas), suggesting a superficial, global facial analysis. In contrast, ERPs of adults revealed an FIE at later processing stages (i.e. N170; generated in face‐selective, higher visual areas). Interestingly, adolescents showed FIEs in both processing stages, suggesting a hybrid developmental stage. Furthermore, adolescents and adults showed FIEs for stimuli containing low SF information, whereas such effects were driven by both low and high SF information in children. These results indicate that face processing has a protracted maturational course into adolescence, and is dependent on changes in SF processing. During adolescence, sensitivity to configural cues is developed, which aids the fast and holistic processing that is so special for faces.     

The role of neurogenesis during development and in the adult brain

Neural stem cells (NSCs) give rise to neurons during development. NSCs persist and neurogenesis continues in restricted regions of postnatal and adult brains. Adult‐born neurons integrate into existing neural circuits by synaptic connections and participate in the regulation of brain function. Thus, understanding NSCs and neurogenesis may be crucial in the development of new strategies for brain repair. Here, we introduce the lineage of NSCs from embryonic to adult stages and summarize recent studies on maturation and integration of adult‐born neurons. We also discuss the regulation and potential functions of adult neurogenesis in physiological and pathological conditions.     

Expression of the postsynaptic scaffold PSD‐95 and development of synaptic physiology during giant terminal formation in the auditory brainstem of the chicken

In the avian nucleus magnocellularis (NM) endbulb of Held giant synapses develop from temporary bouton terminals. The molecular regulation of this process is not well understood. Furthermore, it is unknown how the postsynaptic specialization of the endbulb synapses develops. We therefore analysed expression of the postsynaptic scaffold protein PSD‐95 during the transition from bouton‐to‐endbulb synapses. PSD‐95 has been implicated in the regulation of the strength of glutamatergic synapses and could accordingly be of functional relevance for giant synapse formation. PSD‐95 protein was expressed at synaptic sites in embryonic chicken auditory brainstem and upregulated between embryonic days (E)12 and E16. We applied immunofluorescence staining and confocal microscopy to quantify pre‐and postsynaptic protein signals during bouton‐to‐endbulb transition. Giant terminal formation progressed along the tonotopic axis in NM, but was absent in low‐frequency NM. We found a tonotopic gradient of postsynaptic PSD‐95 signals in NM. Furthermore, PSD‐95 immunosignals showed the greatest increase between E12 and E15, temporally preceding the bouton‐to‐endbulb transition. We then applied whole‐cell electrophysiology to measure synaptic currents elicited by synaptic terminals during bouton‐to‐endbulb transition. With progressing endbulb formation postsynaptic currents rose more rapidly and synapses were less susceptible to short‐term depression, but currents were not different in amplitude or decay‐time constant. We conclude that development of presynaptic specializations follows postsynaptic development and speculate that the early PSD‐95 increase could play a functional role in endbulb formation.     

Rostro‐caudal maturation of glial cells in the accessory olfactory system during development: involvement in outgrowth of GnRH neurites

During mammalian embryonic development, GnRH neurones differentiate from the nasal placode and migrate through the nasal septum towards the forebrain. We previously showed that a category of glial cells, the olfactory ensheathing cells (OEC), forms the microenvironment of migrating GnRH neurones. Here, to characterize the quantitative and qualitative importance of this glial, we investigated the spatiotemporal maturation of glial cells in situ and the role of maturing glia in GnRH neurones development ex vivo. More than 90% of migrating GnRH neurones were found to be associated with glial cells. There was no change in the cellular microenvironment of GnRH neurones in the regions crossed during embryonic development as glial cells formed the main microenvironment of these neurones (53.4%). However, the phenotype of OEC associated with GnRH neurones changed across regions. The OEC progenitors immunoreactive to brain lipid binding protein formed the microenvironment of migrating GnRH neurones from the vomeronasal organ to the telencephalon and were also present in the diencephalon. However, during GnRH neurone migration, maturation of OEC to [GFAP+] state (glial fibrillary acid protein) was only observed in the nasal septum. Inducing depletion of OEC in maturation, using transgenic mice expressing herpes simplex virus thymidine kinase driven by the GFAP promoter, had no impact on neurogenesis or on triggering GnRH neurones migration in nasal explant culture. Nevertheless, depletion of [GFAP+] cells decreased GnRH neurites outgrowth by 57.4%. This study suggests that specific maturation of OEC in the nasal septum plays a role in morphological differentiation of GnRH neurones.     

Cellular and molecular mechanisms controlling the migration of neocortical interneurons

The discovery, approximately 15 years ago, that cortical GABAergic interneurons originate outside the pallium has revolutionized our understanding of the development of the cerebral cortex. It is now clear that glutamatergic pyramidal cells and GABAergic interneurons follow largely distinct development programs, a notion that has challenged our views on how these neurons assemble to form precise neural circuits. In this review, I summarize our current knowledge of the mechanisms that control the migration of neocortical interneurons, a process that can be subdivided into three consecutive phases: migration to the cortex, intracortical dispersion, and layering.     

人胚早期神经管细胞凋亡因子的表达

Neural tube development comprises neural induction,neural epithelial cell proliferation,and apoptosis,as well as migration of nerve cells.Too much or too little apoptosis leads to abnormal nervous system development.The present study analyzed expression and distribution of apoptotic-related factors,including Fas,FasL,and caspase-3,during human embryonic neural tube development.Experimental results showed that increased caspase-3 expression promoted neural apoptosis via a mitochondrial-mediated intrinsic pathway at 4 weeks during early human embryonic neural tube development.Subsequently,Fas and FasL expression increased during embryonic development.The results suggest that neural cells influence neural apoptosis through synergistic effects of extrinsic pathways.Therefore,neural apoptosis during the early period of neural tube development in the human embryo might be regulated by the death receptor induced apoptotic extrinsic pathways.     

Nerve‐racking – apoptotic and non‐apoptotic roles of caspases in the nervous system of Drosophila

Studies using Drosophila as a model system have contributed enormously to our knowledge of caspase function and regulation. Caspases are best known as central executioners of apoptosis but also control essential physiological processes in a non‐apoptotic manner. The Drosophila genome codes for seven caspases and in this review we provide an overview of current knowledge about caspase function in the nervous system. Caspases regulate neuronal death at all developmental stages and in various neuronal populations. In contrast, non‐apoptotic roles are less well understood. The development of new genetically encoded sensors for caspase activity provides unprecedented opportunities to study caspase function in the nervous system in more detail. In light of these new tools we discuss the potential of Drosophila as a model to discover new apoptotic and non‐apoptotic neuronal roles of caspases.     

The value of interleukin-12B (p40) gene promoter polymorphism in patients with schizophrenia in a region of East Turkey

Aims: It has been hypothesized that the activation of the immune system may be involved in the neuropathological changes occurring in the central nervous system of schizophrenic patients. Cytokines play a key role in the activation of the immune system. Moreover, they strongly influence the dopaminergic, noradrenergic and serotonergic neurotransmission. To the best of our knowledge, in schizophrenic patients, plasma levels of interleukin (IL)‐12 were investigated only in one study, where deregulation of IL‐12 was determined. However, genotypical variations of the IL‐12B (p40) gene have not been investigated for schizophrenic patients yet. Therefore, in the present study, we aimed to examine polymorphic variants of IL‐12B (p40) gene promoter region in patients with schizophrenia in a population of the Elazig Region of East Anatolia, Turkey. Methods: One hundred Turkish patients diagnosed with schizophrenia based on the Diagnostic and Statistical Manual of Mental Disorders (DSM‐IV), and 116 healthy control subjects participated in the present study. The genotype characteristics were determined by polymerase chain reaction‐based restriction fragment length polymorphism method using DNA extracted from peripheral blood. Results: Significant differences in both the genotype and allele frequencies were found between schizophrenia patients and control groups (P < 0.01). Conclusions: These findings may support the hypothesis that activation of the inflammatory response system and in particular, of Th‐1 cells, is involved in the pathophysiology of schizophrenia. We think that this study is the first trial associated with IL‐12 cytokine at the molecular genetic level on immune mechanisms for neuropsychiatric disorders including schizophrenia, and this perspective and the role of the cytokines in the pathogenesis of schizophrenia may constitute a reasonable target for the present and future treatment strategies and prognosis.     

Synapse formation changes the rules for desensitization of PKC translocation in Aplysia

Protein kinase Cs (PKCs) are activated by translocating from the cytoplasm to the membrane. We have previously shown that serotonin‐mediated translocation of PKC to the plasma membrane in Aplysia sensory neurons was subject to desensitization, a decrease in the ability of serotonin to induce translocation after previous application of serotonin. In Aplysia, changes in the strength of the sensory–motor neuron synapse are important for behavioral sensitization and PKC regulates a number of important aspects of this form of synaptic plasticity. We have previously suggested that the desensitization of PKC translocation in Aplysia sensory neurons may partially explain the differences between spaced and massed training, as spaced applications of serotonin, a cellular analog of spaced training, cause greater desensitization of PKC translocation than one massed application of serotonin, a cellular analog of massed training. Our previous studies were performed in isolated sensory neurons. In the present study, we monitored translocation of fluorescently‐tagged PKC to the plasma membrane in living sensory neurons that were co‐cultured with motor neurons to allow for synapse formation. We show that desensitization now becomes similar during spaced and massed applications of serotonin. We had previously modeled the signaling pathways that govern desensitization in isolated sensory neurons. We now modify this mathematical model to account for the changes observed in desensitization dynamics following synapse formation. Our study shows that synapse formation leads to significant changes in the molecular signaling networks that underlie desensitization of PKC translocation.     

The generation of theta rhythm in hippocampal formation maintained in vitro

The most spectacular example of oscillations and synchrony which appear in the brain is the rhythmic slow activity (theta) of the limbic cortex. Theta rhythm is the best synchronized electroencephalographic activity that can be recorded from the mammalian brain. Hippocampal formation is considered to be the main structure involved in the generation of this activity. Although detailed studies of the physiology and pharmacology of theta‐band oscillations have been carried out since the early 1950s, the first demonstration of atropine‐sensitive theta rhythm, recorded in completely deafferented hippocampal slices of a rat, was performed in the second half of the 1980s. Since the discovery of cholinergically induced in vitro theta rhythm recorded from hippocampal formation slices, the central mechanisms underlying theta generation have been successfully studied in in vitro conditions. Most of these experiments were focused on the basic question regarding the similarities between the cholinergically induced theta activity and theta rhythm examined in vivo. The results of numerous in vitro experiments strongly suggest that cholinergically induced theta rhythm recorded in hippocampal slices is a useful analogue of theta observed in intact animals, and could be helpful in searching for the mechanisms of oscillations and synchrony in the central nervous system neuronal networks. The objective of the present review is to discuss the main results of experiments concerning theta oscillations recorded in in vitro conditions. It is our intent to provide, on the basis of these results, the characteristics of essential mechanisms underlying the generation of atropine‐sensitive in vitro theta.     

Expression and regulation of golli products of myelin basic protein gene during in vitro development of oligodendrocytes.

The myelin basic protein (MBP) gene produces two families of proteins, the classic MBPs, important for myelination of the CNS, and the golli proteins, whose biological role in oligodendrocytes (OLs) is still unknown. The goals of this work were to study the in vitro pattern of expression of the golli products during OL differentiation and to compare it with that of the classic MBP products of the gene. Mouse primary glial cultures were analyzed at the mRNA and protein levels with an array of techniques. We found that OLs express golli mRNA primarily during intermediate stages of differentiation, which was confirmed by immunocytochemical analysis. Golli expression was low in proliferating OL progenitors as well as in terminally mature OLs. Golli proteins were found associated with the OL cell soma and nuclei and, to a lesser extent, with the cellular processes. We also found that golli proteins are not targeted to myelin in vitro and in vivo, in contrast to the classic MBPs. Finally, we found that golli expression is regulated during OL development and can be manipulated by growth factors such as basic fibroblast growth factor, neurotrophin-3, and retinoic acid.     

Synaptic development of layer V pyramidal neurons in the prenatal human prefrontal neocortex: a Neurolucida-aided Golgi study

The prefrontal neocortex is involved in many high cognitive functions in humans.Deficits in neuronal and neurocircuitry development in this part of the cerebrum have been associated with various neuropsychiatric disorders in adolescents and adults.There are currently little available data regarding prenatal dendrite and spine formation on projecting neurons in the human prefrontal neocortex.Previous studies have demonstrated that Golgi silver staining can identify neurons in the frontal lobe and visual cortex in human embryos.In the present study,five fetal brains,at 19,20,26,35,and 38 gestational weeks,were obtained via the body donation program at Xiangya School of Medicine,Central South University,China.Golgi-stained pyramidal neurons in layer V of Brodmann area 46 in fetuses were quantitatively analyzed using the Neurolucida morphometry system.Results revealed that somal size,total dendritic length,and branching points of these neurons increased from 26 to 38 gestational weeks.There was also a large increase in dendritic spines from 35 to 38 gestational weeks.These findings indicate that,in the human prefrontal neocortex,dendritic growth in layer V pyramidal neurons occurs rapidly during the third trimester of gestation.The use of human fetal brain tissue was approved by the Animal Ethics Committee of Xiangya School of Medicine,Central South University,China(approval No.2011-045)on April 5,2011.