Regulated Translation Initiation Controls Stress-Induced Gene Expression in Mammalian Cells

The addition to proteins of the negatively charged polymer of ADP-ribose (PAR), which is synthesized by PAR polymerases (PARPs) from NAD(+), is a unique post-translational modification. It regulates not only cell survival and cell-death programmes, but also an increasing number of other biological functions with which novel members of the PARP family have been associated. These functions include transcriptional regulation, telomere cohesion and mitotic spindle formation during cell division, intracellular trafficking and energy metabolism.

Poly(ADP-ribose): novel functions for an old molecule.

Transcription is a molecular requisite for long-term synaptic plasticity and long-term memory formation. Thus, in the last several years, one main interest of molecular neuroscience has been the identification of families of transcription factors that are involved in both of these processes. Transcription is a highly regulated process that involves the combined interaction and function of chromatin and many other proteins, some of which are essential for the basal process of transcription, while others control the selective activation or repression of specific genes. These regulated interactions ultimately allow a sophisticated response to multiple environmental conditions, as well as control of spatial and temporal differences in gene expression. Evidence based on correlative changes in expression, genetic mutations, and targeted molecular inhibition of gene expression have shed light on the function of transcription in both synaptic plasticity and memory formation. This review provides a brief overview ...

/pdf/transcription-factors-in-long-term-memory-and-synaptic-4mi8iwqc3p.pdf

Transcription Factors in Long-Term Memory and Synaptic Plasticity

https://www.cell.com/neuron/pdf/S0896-6273(03)00206-X.pdf

Hippocampal LTP Is Accompanied by Enhanced F-Actin Content within the Dendritic Spine that Is Essential for Late LTP Maintenance In Vivo

BDNF: A key regulator for protein synthesis-dependent LTP and long-term memory?

Maintenance of long-term potentiation (LTP) requires de novo gene expression. Here we report the direct isolation, using PCR-differential display, of genes whose expression level was altered after induction of long-lasting LTP in the hippocampus of freely moving awake rats. Differential display using 480 primer combinations revealed 17 cDNA bands that showed a reproducible change in expression level. These cDNAs represented at least 10 different genes (termed RM1-10), all of which showed up-regulation at 75 min after LTP induction and a return to basal expression levels within 24 h. Three of these genes were known only from expressed sequence tags (RM1-3), two were known genes whose up-regulation by LTP has not been described (GADD153/CHOP and ler5), and five were known genes whose up-regulation by LTP has already been reported (MAPK phosphatase, NGFI-A/zif268, vesl-1S/homer-1a, Ag2, and krox-20). We characterized the expression profiles of genes in the two former categories with respect to NMDA receptor dependency, tissue specificity, and developmental regulation using northern blotting and semiquantitative RT-PCR. The up-regulation of all five of these genes was NMDA receptor-dependent and correlated with the persistence of LTP, suggesting that these genes may play functional roles in prolonged LTP maintenance.

https://onlinelibrary.wiley.com/doi/pdf/10.1046/j.1471-4159.2000.0742239.x

Identification and Cataloging of Genes Induced by Long‐Lasting Long‐Term Potentiation in Awake Rats

We report NMDA receptor-dependent expression of synaptopodin mRNA in the dentate granule cells of the hippocampus following induction of long-term potentiation (LTP) in vivo. Synaptopodin did not belong to immediate-early genes, as de novo protein synthesis was required for the induction of synaptopodin gene transcription. An increased level of synaptopodin mRNA was observed at 75 min and 3.5 h after the onset of LTP. Importantly, there was correlation between the induction of mRNA expression and the persistence of LTP. Synaptopodin immunoreactivity was elevated specifically in synaptic layers, middle and outer molecular layers of dentate gyrus where LTP was induced. As synaptopodin is an actin-associated protein present in spine neck and implicated in the modulation of cell morphology, our results suggest that synaptopodin, by regulating the dynamics of the actin cytoskeleton, contributes to the morphological change in spine shape considered to be important for the maintenance of synaptic plasticity.

Regulated expression of an actin-associated protein, synaptopodin, during long-term potentiation

The terrestrial slug Limax has a highly developed ability to associate the odor of some foods (e.g., carrot juice) with aversive stimuli such as the bitter taste of quinidine solution. The procerebrum (PC) is a part of the slug’s brain thought to be involved in odor-aversion learning, but direct evidence is still lacking. Here we present evidence showing that the PC is essential for odor-aversion learning. Unlike sham-operated slugs, PC ablation 7 d prior to conditioning showed that most slugs did not avoid carrot juice in the memory retention test conducted 24 h after the conditioning. Slugs with the PC ablated 3 h, 1 d, 3 d, or 7 d after conditioning and examined by the memory retention test at 3 d after the PC ablation were also less likely to avoid carrot juice than sham-operated slugs. The PC ablation did not damage the ability of the slugs to sense attractive odor (everyday food) or innately aversive odor (onion or garlic). These results demonstrate that the PC is a necessary component in the retention and/or retrieval of odor-aversion memory.

/pdf/the-procerebrum-is-necessary-for-odor-aversion-learning-in-3jk8ztip5h.pdf

Ryota Matsuo

Papers

Identification and Cataloging of Genes Induced by Long‐Lasting Long‐Term Potentiation in Awake Rats

Regulated expression of an actin-associated protein, synaptopodin, during long-term potentiation

The procerebrum is necessary for odor-aversion learning in the terrestrial slug Limax valentianus

A novel nitric oxide synthase expressed specifically in the olfactory center.

Genomic structure of nitric oxide synthase in the terrestrial slug is highly conserved.