Ist das Bewusstsein "Herr im eigenen Haus"? : Benjamin Libet erklärt, wie das Gehirn Bewusstsein erzeugt

Rezension zu: Benjamin Libet : Mind Time – Wie das Gehirn Bewusstsein produziert, Suhrkamp Verlag, Frankfurt, 2005, ISBN 3-518-58427-8, 308 Seiten, 19,80 Euro

Dopamine Modulates Homeostatic Excitatory Synaptic Plasticity of Immature Dentate Granule Cells in Entorhino-Hippocampal Slice Cultures

Homeostatic plasticity mechanisms maintain neurons in a stable state. To what extent these mechanisms are relevant during the structural and functional maturation of neural tissue is poorly understood. To reveal developmental changes of a major homeostatic plasticity mechanism, i.e., homeostatic excitatory synaptic plasticity, we analyzed 1-week- and 4-week-old entorhino-hippocampal slice cultures and investigated the ability of immature and mature dentate granule cells (GCs) to express this form of plasticity. Our experiments demonstrate that immature GCs are capable of adjusting their excitatory synaptic strength in a compensatory manner at early postnatal stages, i.e., in 1-week-old preparations, as is the case for mature GCs. This ability of immature dentate GCs is absent in 4-week-old slice cultures. Further investigations into the signaling pathways reveal an important role of dopamine (DA), which prevents homeostatic synaptic up-scaling of immature GCs in young cultures, whereas it does not affect immature and mature GCs in 4-week-old preparations. Together, these results disclose the ability of immature GCs to express homeostatic synaptic plasticity during early postnatal development. They hint toward a novel role of dopaminergic signaling, which may gate activity-dependent changes of newly born neurons by blocking homeostasis

FIDEL—a retrovirus-like retrotransposon and its distinct evolutionary histories in the A- and B-genome components of cultivated peanut

In this paper, we describe a Ty3-gypsy retrotransposon from allotetraploid peanut (Arachis hypogaea) and its putative diploid ancestors Arachis duranensis (A-genome) and Arachis ipaënsis (B-genome). The consensus sequence is 11,223 bp. The element, named FIDEL (Fairly long Inter-Dispersed Euchromatic LTR retrotransposon), is more frequent in the A- than in the B-genome, with copy numbers of about 3,000 (±950, A. duranensis), 820 (±480, A. ipaënsis), and 3,900 (±1,500, A. hypogaea) per haploid genome. Phylogenetic analysis of reverse transcriptase sequences showed distinct evolution of FIDEL in the ancestor species. Fluorescent in situ hybridization revealed disperse distribution in euchromatin and absence from centromeres, telomeric regions, and the nucleolar organizer region. Using paired sequences from bacterial artificial chromosomes, we showed that elements appear less likely to insert near conserved ancestral genes than near the fast evolving disease resistance gene homologs. Within the Ty3-gypsy elements, FIDEL is most closely related with the Athila/Calypso group of retrovirus-like retrotransposons. Putative transmembrane domains were identified, supporting the presence of a vestigial envelope gene. The results emphasize the importance of FIDEL in the evolution and divergence of different Arachis genomes and also may serve as an example of the role of retrotransposons in the evolution of legume genomes in general

Synaptic Plasticity and Excitation-Inhibition Balance in the Dentate Gyrus: Insights from In Vivo Recordings in Neuroligin-1, Neuroligin-2, and Collybistin Knockouts

The hippocampal dentate gyrus plays a role in spatial learning and memory and is thought to encode differences between similar environments. The integrity of excitatory and inhibitory transmission and a fine balance between them is essential for efficient processing of information. Therefore, identification and functional characterization of crucial molecular players at excitatory and inhibitory inputs is critical for understanding the dentate gyrus function. In this minireview, we discuss recent studies unraveling molecular mechanisms of excitatory/inhibitory synaptic transmission, long-term synaptic plasticity, and dentate granule cell excitability in the hippocampus of live animals. We focus on the role of three major postsynaptic proteins localized at excitatory (neuroligin-1) and inhibitory synapses (neuroligin-2 and collybistin). In vivo recordings of field potentials have the advantage of characterizing the effects of the loss of these proteins on the input-output function of granule cells embedded in a network with intact connectivity. The lack of neuroligin-1 leads to deficient synaptic plasticity and reduced excitation but normal granule cell output, suggesting unaltered excitation-inhibition ratio. In contrast, the lack of neuroligin-2 and collybistin reduces inhibition resulting in a shift towards excitation of the dentate circuitry

Subcellular vesicular aggregations of GABA(B) R1a and R1b receptors increase with age in neurons of the developing mouse brain

GABA(B) receptors play a critical neuromodulatory role in the central nervous system. It has been suggested that both the functional role and the cellular distribution of GABA(B) receptors in the neuronal network change during post-natal maturation. In the present study, the cellular and subcellular distribution patterns of the GABA(B) R1a/b receptors have been analysed in different brain regions of the mouse using immunocytochemistry with isoform-specific antisera. GABA(B) R1-immunoreactivity (IR) was present from the first post-natal day (P0) on in most regions of the brain. Neurones exhibited diffuse GABA(B) R1-IR labelling throughout somata and larger proximal dendrites as well as some fine neuronal processes. After P5, distinct punctuated staining was apparent. The number of such GABA(B) IR granules per cell increased with age in a sigmoidal manner from P5 to P60. Electron microscopy revealed GABA(B) IR as clusters of small clear vesicles of 30 - 50 nm diameter within the cytoplasm and close to the cell membrane at extrasynaptic locations, as well as at pre-synaptic and post-synaptic specialisations. The increase in GABA(B) R1-IR punctuate staining during brain maturation points to increasing functional participation and heterogeneity of GABA(B) receptors as the complexity of the central nervous system expands with growth and development

T2N as a new tool for robust electrophysiological modeling demonstrated for mature and adult-born dentate granule cells

Compartmental models are the theoretical tool of choice for understanding single neuron computations. However, many models are incomplete, built ad hoc and require tuning for each novel condition rendering them of limited usability. Here, we present T2N, a powerful interface to control NEURON with Matlab and TREES toolbox, which supports generating models stable over a broad range of reconstructed and synthetic morphologies. We illustrate this for a novel, highly detailed active model of dentate granule cells (GCs) replicating a wide palette of experiments from various labs. By implementing known differences in ion channel composition and morphology, our model reproduces data from mouse or rat, mature or adult-born GCs as well as pharmacological interventions and epileptic conditions. This work sets a new benchmark for detailed compartmental modeling. T2N is suitable for creating robust models useful for large-scale networks that could lead to novel predictions. We discuss possible T2N application in degeneracy studies.Fil: Beining, Marcel. Ernst Strungmann Institute; Alemania. Frankfurt Institute for Advanced Studies; Alemania. Goethe Universitat Frankfurt; AlemaniaFil: Mongiat, Lucas Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte. Instituto de Investigaciones en Biodiversidad y Medioambiente. Universidad Nacional del Comahue. Centro Regional Universidad Bariloche. Instituto de Investigaciones en Biodiversidad y Medioambiente; ArgentinaFil: Schwarzacher, Stephan Wolfgang. Goethe Universitat Frankfurt; AlemaniaFil: Cuntz, Hermann. Frankfurt Institute for Advanced Studies; Alemania. Ernst Strungmann Institute; AlemaniaFil: Jedlicka, Peter. Goethe Universitat Frankfurt; Alemani

Differential postnatal expression of neuronal maturation markers in the dentate gyrus of mice and rats

The dentate gyrus (DG) is a unique structure of the hippocampus that is distinguished by ongoing neurogenesis throughout the lifetime of an organism. The development of the DG, which begins during late gestation and continues during the postnatal period, comprises the structural formation of the DG as well as the establishment of the adult neurogenic niche in the subgranular zone (SGZ). We investigated the time course of postnatal maturation of the DG in male C57BL/6J mice and male Sprague-Dawley rats based on the distribution patterns of the immature neuronal marker doublecortin (DCX) and a marker for mature neurons, calbindin (CB). Our findings demonstrate that the postnatal DG is marked by a substantial maturation with a high number of DCX-positive granule cells (GCs) during the first two postnatal weeks followed by a progression toward more mature patterns and increasing numbers of CB-positive GCs within the subsequent 2 weeks. The most substantial shift in maturation of the GC population took place between P7 and P14 in both mice and rats, when young, immature DCX-positive GCs became confined to the innermost part of the GC layer (GCL), indicative of the formation of the SGZ. These results suggest that the first month of postnatal development represents an important transition phase during which DG neurogenesis and the maturation course of the GC population becomes analogous to the process of adult neurogenesis. Therefore, the postnatal DG could serve as an attractive model for studying a growing and functionally maturing neural network. Direct comparisons between mice and rats revealed that the transition from immature DCX-positive to mature CB-positive GCs occurs more rapidly in the rat by approximately 4–6 days. The remarkable species difference in the speed of maturation on the GC population level may have important implications for developmental and neurogenesis research in different rodent species and strains

Differential Postnatal Expression of Neuronal Maturation Markers in the Dentate Gyrus of Mice and Rats

The dentate gyrus (DG) is a unique structure of the hippocampus that is distinguished by ongoing neurogenesis throughout the lifetime of an organism. The development of the DG, which begins during late gestation and continues during the postnatal period, comprises the structural formation of the DG as well as the establishment of the adult neurogenic niche in the subgranular zone (SGZ). We investigated the time course of postnatal maturation of the DG in male C57BL/6J mice and male Sprague-Dawley rats based on the distribution patterns of the immature neuronal marker doublecortin (DCX) and a marker for mature neurons, calbindin (CB). Our findings demonstrate that the postnatal DG is marked by a substantial maturation with a high number of DCX-positive granule cells (GCs) during the first two postnatal weeks followed by a progression toward more mature patterns and increasing numbers of CB-positive GCs within the subsequent 2 weeks. The most substantial shift in maturation of the GC population took place between P7 and P14 in both mice and rats, when young, immature DCX-positive GCs became confined to the innermost part of the GC layer (GCL), indicative of the formation of the SGZ. These results suggest that the first month of postnatal development represents an important transition phase during which DG neurogenesis and the maturation course of the GC population becomes analogous to the process of adult neurogenesis. Therefore, the postnatal DG could serve as an attractive model for studying a growing and functionally maturing neural network. Direct comparisons between mice and rats revealed that the transition from immature DCX-positive to mature CB-positive GCs occurs more rapidly in the rat by approximately 4–6 days. The remarkable species difference in the speed of maturation on the GC population level may have important implications for developmental and neurogenesis research in different rodent species and strains

Enhanced LTP of population spikes in the dentate gyrus of mice haploinsufficient for neurobeachin

Deletion of the autism candidate molecule neurobeachin (Nbea), a large PH-BEACH-domain containing neuronal protein, has been shown to affect synaptic function by interfering with neurotransmitter receptor targeting and dendritic spine formation. Previous analysis of mice lacking one allele of the Nbea gene identified impaired spatial learning and memory in addition to altered autism-related behaviours. However, no functional data from living heterozygous Nbea mice (Nbea+/−) are available to corroborate the behavioural phenotype. Here, we explored the consequences of Nbea haploinsufficiency on excitation/inhibition balance and synaptic plasticity in the intact hippocampal dentate gyrus of Nbea+/− animals in vivo by electrophysiological recordings. Based on field potential recordings, we show that Nbea+/− mice display enhanced LTP of the granule cell population spike, but no differences in basal synaptic transmission, synapse numbers, short-term plasticity, or network inhibition. These data indicate that Nbea haploinsufficiency causes remarkably specific alterations to granule cell excitability in vivo, which may contribute to the behavioural abnormalities in Nbea+/− mice and to related symptoms in patients