Ndel1 and Reelin Maintain Postnatal CA1 Hippocampus Integrity

How the integrity of laminar structures in the postnatal brain is maintained impacts neuronal functions. Ndel1, the mammalian homolog of NuDE from the filamentous fungus Aspergillus nidulans, is an atypical microtubule (MT)-associated protein that was initially investigated in the contexts of neurogenesis and neuronal migration. Constitutive knock-out mice for Ndel1 are embryonic lethal, thereby necessitating the creation a conditional knock-out to probe the roles of Ndel1 in postnatal brains. Here we report that CA1 pyramidal neurons from mice postnatally lacking Ndel1 (Ndel1 conditional knock-out) exhibit fragmented MTs, dendritic/synaptic pathologies, are intrinsically hyperexcitable and undergo dispersion independently of neuronal migration defect. Secondary to the pyramidal cell changes is the decreased inhibitory drive onto pyramidal cells from interneurons. Levels of the glycoprotein Reelin that regulates MTs, neuronal plasticity, and cell compaction are significantly reduced in hippocampus of mutant mice. Strikingly, a single injection of Reelin into the hippocampus of Ndel1 conditional knock-out mice ameliorates ultrastructural, cellular, morphological, and anatomical CA1 defects. Thus, Ndel1 and Reelin contribute to maintain postnatal CA1 integrity.1112Ysciescopu

Impact of Dendritic Size and Dendritic Topology on Burst Firing in Pyramidal Cells

Neurons display a wide range of intrinsic firing patterns. A particularly relevant pattern for neuronal signaling and synaptic plasticity is burst firing, the generation of clusters of action potentials with short interspike intervals. Besides ion-channel composition, dendritic morphology appears to be an important factor modulating firing pattern. However, the underlying mechanisms are poorly understood, and the impact of morphology on burst firing remains insufficiently known. Dendritic morphology is not fixed but can undergo significant changes in many pathological conditions. Using computational models of neocortical pyramidal cells, we here show that not only the total length of the apical dendrite but also the topological structure of its branching pattern markedly influences inter- and intraburst spike intervals and even determines whether or not a cell exhibits burst firing. We found that there is only a range of dendritic sizes that supports burst firing, and that this range is modulated by dendritic topology. Either reducing or enlarging the dendritic tree, or merely modifying its topological structure without changing total dendritic length, can transform a cell's firing pattern from bursting to tonic firing. Interestingly, the results are largely independent of whether the cells are stimulated by current injection at the soma or by synapses distributed over the dendritic tree. By means of a novel measure called mean electrotonic path length, we show that the influence of dendritic morphology on burst firing is attributable to the effect both dendritic size and dendritic topology have, not on somatic input conductance, but on the average spatial extent of the dendritic tree and the spatiotemporal dynamics of the dendritic membrane potential. Our results suggest that alterations in size or topology of pyramidal cell morphology, such as observed in Alzheimer's disease, mental retardation, epilepsy, and chronic stress, could change neuronal burst firing and thus ultimately affect information processing and cognition