Irregular distribution of grid cell firing fields in rats exploring a 3D volumetric space

We investigated how entorhinal grid cells encode volumetric space. On a horizontal surface, grid cells usually produce multiple, spatially focal, approximately circular firing fields that are evenly sized and spaced to form a regular, close-packed, hexagonal array. This spatial regularity has been suggested to underlie navigational computations. In three dimensions, theoretically the equivalent firing pattern would be a regular, hexagonal close packing of evenly sized spherical fields. In the present study, we report that, in rats foraging in a cubic lattice, grid cells maintained normal temporal firing characteristics and produced spatially stable firing fields. However, although most grid fields were ellipsoid, they were sparser, larger, more variably sized and irregularly arranged, even when only fields abutting the lower surface (equivalent to the floor) were considered. Thus, grid self-organization is shaped by the environment’s structure and/or movement affordances, and grids may not need to be regular to support spatial computations.

Activity-Dependent Gene Expression in Neurons

The function of the nervous system in conveying and processing information necessary to interact with the environment confers unique aspects on how the expression of genes in neurons is regulated. Three salient factors are that (1) neurons are the largest and among the most morphologically complex of all cells, with strict polarity, subcellular compartmentation, and long-distant transport of gene products, signaling molecules, and other materials; (2) information is coded in the temporal firing pattern of membrane depolarization; and (3) neurons must maintain a stable homeostatic level of activation to function so stimuli do not normally drive intracellular signaling to steady state. Each of these factors can require special methods of analysis differing from approaches used in non-neuronal cells. This review considers these three aspects of neuronal gene expression and the current approaches being used to analyze these special features of how the neuronal transcriptome is modulated by action potential firing.

Phrenic motoneurons: output elements of a highly organized intraspinal network

pontomedullary respiratory network generates the respiratory pattern and relays it to bulbar and spinal respiratory motor outputs. The phrenic motor system controlling diaphragm contraction receives and processes descending commands to produce orderly, synchronous, and cycle-to-cycle-reproducible spatiotemporal firing. Multiple investigators have studied phrenic motoneurons (PhMNs) in an attempt to shed light on local mechanisms underlying phrenic pattern formation. I and colleagues (Marchenko V, Ghali MG, Rogers RF. Am J Physiol Regul Integr Comp Physiol 308: R916–R926, 2015.) recorded PhMNs in unanesthetized, decerebrate rats and related their activity to simultaneous phrenic nerve (PhN) activity by creating a time-frequency representation of PhMN-PhN power and coherence. On the basis of their temporal firing patterns and relationship to PhN activity, we categorized PhMNs into three classes, each of which emerges as a result of intrinsic biophysical and network properties and organizes the orderly contraction of diaphragm motor fibers. For example, early inspiratory diaphragmatic activation by the early coherent burst generated by high-frequency PhMNs may be necessary to prime it to overcome its initial inertia. We have also demonstrated the existence of a prominent role for local intraspinal inhibitory mechanisms in shaping phrenic pattern formation. The objective of this review is to relate and synthesize recent findings with those of previous studies with the aim of demonstrating that the phrenic nucleus is a region of active local processing, rather than a passive relay of descending inputs.

YAP controls retinal stem cell DNA replication timing and genomic stability

The adult frog retina retains a reservoir of active neural stem cells that contribute to continuous eye growth throughout life. We found that Yap, a downstream effector of the Hippo pathway, is specifically expressed in these stem cells. Yap knock-down leads to an accelerated S-phase and an abnormal progression of DNA replication, a phenotype likely mediated by upregulation of c-Myc. This is associated with an increased occurrence of DNA damage and eventually p53-p21 pathway-mediated cell death. Finally, we identified PKNOX1, a transcription factor involved in the maintenance of genomic stability, as a functional and physical interactant of YAP. Altogether, we propose that YAP is required in adult retinal stem cells to regulate the temporal firing of replication origins and quality control of replicated DNA. Our data reinforce the view that specific mechanisms dedicated to S-phase control are at work in stem cells to protect them from genomic instability.