A coming-of-age story: adult neurogenesis or adolescent neurogenesis in rodents?

It is surprising that after more than a century using rodents for scientific research, there are no clear, consensual, or consistent definitions for when a mouse or a rat becomes adult. Specifically, in the field of adult hippocampal neurogenesis, where this concept is central, there is a trend to consider that puberty marks the start of adulthood and is not uncommon to find 30-day-old mice being described as adults. However, as others discussed earlier, this implies an important bias in the perceived importance of this trait because functional studies are normally done at very young ages, when neurogenesis is at its peak, disregarding middle aged and old animals that exhibit very little generation of new neurons. In this feature article we elaborate on those issues and argue that research on the postnatal development of mice and rats in the last 3 decades allows to establish an adolescence period that marks the transition to adulthood, as occurs in other mammals. Adolescence in both rat and mice ends around postnatal day 60 and therefore this age can be considered the onset of adulthood in both species. Nonetheless, to account for inter-individual, inter-strain differences in maturation and for possible delays due to environmental and social conditions, 3 months of age might be a safer option to consider mice and rats bona fide adults, as suggested by The Jackson Labs

Epigenetic stability in the adult mouse cortex under conditions of pharmacologically induced histone acetylation

Histone acetylation is considered a major epigenetic process that affects brain development and synaptic plasticity, as well as learning and memory. The transcriptional effectors and morphological changes responsible for plasticity as a result of long-term modifications to histone acetylation are not fully understood. To this end, we pharmacologically inhibited histone deacetylation using Trichostatin A in adult (6-month-old) mice and found significant increases in the levels of the acetylated histone marks H3Lys9, H3Lys14 and H4Lys12. High-resolution transcriptome analysis of diverse brain regions uncovered few differences in gene expression between treated and control animals, none of which were plasticity related. Instead, after increased histone acetylation, we detected a large number of novel transcriptionally active regions, which correspond to long non-coding RNAs (lncRNAs). We also surprisingly found no significant changes in dendritic spine plasticity in layers 1 and 2/3 of the visual cortex using long-term in vivo two-photon imaging. Our results indicate that chronic pharmacologically induced histone acetylation can be decoupled from gene expression and instead, may potentially exert a post-transcriptional effect through the differential production of lncRNAs.Natural Sciences and Engineering Research Council of Canada (Postgraduate Fellowship 403855-2011)Yale University. Department of PsychologyYale University. Kavli Institute for Neuroscienc

Correlation between the number of interstitial neurons of the white matter and number of neurons within cortical layers: Histological analyses in postnatal macaque

We have examined the number and distribution of NeuN‐immunoreactive cortical white matter interstitial cells (WMICs) and compared them to the neurons in layers 1–6 across the overlying cortex in coronal sections from postnatal macaques. The data have been gathered from over 300 selected regions at gyral crowns, at sulci, and at linear regions of the cortex where we also determined cortical layer thicknesses: standard thicknesses and tangential thicknesses. Cortical thicknesses and cell numbers showed variability according to gyral, linear, or sulcal regions. In spite of these variations, our standardized cell numbers in layers 1 to 6b and interstitial cells underlying layer 6b‐white matter boundary have shown a consistent correlation between the number of WMICs and the number of layer 5 and 6a cortical neurons on all cortical regions studied: for each WMIC, there are on the order of five cortical neurons in layer 5 and approximately three cortical neurons in layer 6a, irrespective of the origins of the selected cortical area or whether they are from gyral, linear, or sulcal regions. We propose that the number of interstitial neurons in the postnatal macaque cortex is correlated to the density of neurons within layers 5 and 6a and, from a clinical perspective, the change in density or distribution of interstitial neurons in schizophrenia or epilepsy may in fact be linked to the number of layers 5 and 6a neurons

Extraordinary neoteny of synaptic spines in the human prefrontal cortex

The major mechanism for generating diversity of neuronal connections beyond their genetic determination is the activity-dependent stabilization and selective elimination of the initially overproduced synapses [Changeux JP, Danchin A (1976) Nature 264:705-712]. The largest number of supranumerary synapses has been recorded in the cerebral cortex of human and nonhuman primates. It is generally accepted that synaptic pruning in the cerebral cortex, including prefrontal areas, occurs at puberty and is completed during early adolescence [Huttenlocher PR, et al. (1979) Brain Res 163:195-205]. In the present study we analyzed synaptic spine density on the dendrites of layer IIIC cortico-cortical and layer V cortico-subcortical projecting pyramidal neurons in a large sample of human prefrontal cortices in subjects ranging in age from newborn to 91 y. We confirm that dendritic spine density in childhood exceeds adult values by two- to threefold and begins to decrease during puberty. However, we also obtained evidence that overproduction and developmental remodeling, including substantial elimination of synaptic spines, continues beyond adolescence and throughout the third decade of life before stabilizing at the adult level. Such an extraordinarily long phase of developmental reorganization of cortical neuronal circuitry has implications for understanding the effect of environmental impact on the development of human cognitive and emotional capacities as well as the late onset of human-specific neuropsychiatric disorders

SPARC-like 1 Regulates the Terminal Phase of Radial Glia-Guided Migration in the Cerebral Cortex

Differential adhesion between migrating neurons and transient radial glial fibers enables the deployment of neurons into appropriate layers in the developing cerebral cortex. The identity of radial glial signals that regulate the termination of migration remains unclear. Here, we identified a radial glial surface antigen, SPARC (secreted protein acidic and rich in cysteine)-like 1, distributed predominantly in radial glial fibers passing through the upper strata of the cortical plate (CP) where neurons end their migration. Neuronal migration and adhesion assays indicate that SPARC-like 1 functions to terminate neuronal migration by reducing the adhesivity of neurons at the top of the CP. Cortical neurons fail to achieve appropriate positions in the absence of SPARC-like 1 function in vivo. Together, these data suggest that antiadhesive signaling via SPARC-like 1 on radial glial cell surfaces may enable neurons to recognize the end of migration in the developing cerebral cortex

Microarray analysis of microRNA expression in the developing mammalian brain

BACKGROUND: MicroRNAs are a large new class of tiny regulatory RNAs found in nematodes, plants, insects and mammals. MicroRNAs are thought to act as post-transcriptional modulators of gene expression. In invertebrates microRNAs have been implicated as regulators of developmental timing, neuronal differentiation, cell proliferation, programmed cell death and fat metabolism. Little is known about the roles of microRNAs in mammals. RESULTS: We isolated 18-26 nucleotide RNAs from developing rat and monkey brains. From the sequences of these RNAs and the sequences of the rat and human genomes we determined which of these small RNAs are likely to have derived from stem-loop precursors typical of microRNAs. Next, we developed a microarray technology suitable for detecting microRNAs and printed a microRNA microarray representing 138 mammalian microRNAs corresponding to the sequences of the microRNAs we cloned as well as to other known microRNAs. We used this microarray to determine the profile of microRNAs expressed in the developing mouse brain. We observed a temporal wave of expression of microRNAs, suggesting that microRNAs play important roles in the development of the mammalian brain. CONCLUSION: We describe a microarray technology that can be used to analyze the expression of microRNAs and of other small RNAs. MicroRNA microarrays offer a new tool that should facilitate studies of the biological roles of microRNAs. We used this method to determine the microRNA expression profile during mouse brain development and observed a temporal wave of gene expression of sequential classes of microRNAs

Diversity of Cortical Interneurons in Primates: The Role of the Dorsal Proliferative Niche

Summary Evolutionary elaboration of tissues starts with changes in the genome and location of the stem cells. For example, GABAergic interneurons of the mammalian neocortex are generated in the ventral telencephalon and migrate tangentially to the neocortex, in contrast to the projection neurons originating in the ventricular/subventricular zone (VZ/SVZ) of the dorsal telencephalon. In human and nonhuman primates, evidence suggests that an additional subset of neocortical GABAergic interneurons is generated in the cortical VZ and a proliferative niche, the outer SVZ. The origin, magnitude, and significance of this species-specific difference are not known. We use a battery of assays applicable to the human, monkey, and mouse organotypic cultures and supravital tissue to identify neuronal progenitors in the cortical VZ/SVZ niche that produce a subset of GABAergic interneurons. Our findings suggest that these progenitors constitute an evolutionary novelty contributing to the elaboration of higher cognitive functions in primates

Heat shock factor 2 is a stress‐responsive mediator of neuronal migration defects in models of fetal alcohol syndrome

Fetal alcohol spectrum disorder (FASD) is a frequent cause of mental retardation. However, the molecular mechanisms underlying brain development defects induced by maternal alcohol consumption during pregnancy are unclear. We used normal andHsf2‐deficient mice and cell systems to uncover a pivotal role for heat shock factor 2 (HSF2) in radial neuronal migration defects in the cortex, a hallmark of fetal alcohol exposure. Upon fetal alcohol exposure, HSF2 is essential for the triggering of HSF1 activation, which is accompanied by distinctive post‐translational modifications, and HSF2 steers the formation of atypical alcohol‐specific HSF1–HSF2 heterocomplexes. This perturbs the in vivo binding of HSF2 to heat shock elements (HSEs) in genes that control neuronal migration in normal conditions, such as p35 or the MAPs(microtubule‐associated proteins, such as Dclk1 and Dcx), and alters their expression. In the absence of HSF2, migration defects as well as alterations in gene expression are reduced. Thus, HSF2, as a sensor for alcohol stress in the fetal brain, acts as a mediator of the neuronal migration defects associated with FASD

オンガクゲキ ヒョウゲン カテイ ニオケル ガイテキ ナイテキ ケイショウ ノ イミ : オンガクゲキ キャクホン ツタカズラ コマチデン オ ジレイ トシテ

The purpose of this paper is to consider the meaning of external, internal images in the process of expression on music drama. The major results of this consideration can be summarized as follows: The external image is the "form" of reality, embodiment, that is to say, something visible and audible. On the other hand, the internal image is the simbolic form of idea, imagination, visions, enviromental factor, affect (i. e. substance of consciousness, etc.), that is to say, samething invisible. And the expression in the Music Drama is itself the mental act of representing subject subsisted in emotion and reality from expression, such as singing, acting and the theatrical line, etc..国立情報学研究所『研究紀要公開支援事業』により電子化