c-Fos and neuronal plasticity: the aftermath of Kaczmarek’s theory

Abstract

The development of molecular biology methods in the early 1980s led to a better understanding of the role of transcription factors in mammalian cells. The discovery that some transcription factors are critically important for cells to switch between different functional states was fundamental for modern molecular neurobiology. In the 1980s Leszek Kaczmarek proposed that, analogically to the cell cycle or to cell differentiation, long-term synaptic plasticity, learning, and memory should also require the activity of transcription factors. To test his hypothesis, he focused on c-Fos. His team showed that the c-Fos proto-oncogene is activated by synaptic plasticity and learning, and is required for these phenomena to occur. Subsequent studies showed that timp-1 and mmp-9 are c-Fos effector genes that are required for plasticity. The present review summarizes Kaczmarek's hypothesis and the major evidence that supports it. We also describe the ways in which knowledge of the molecular neurobiology of learning and memory advanced because of Kaczmarek's theory. Finally, we briefly discuss the degree to which his hypothesis holds true today after the discovery of non-coding RNAs, a novel class of regulatory molecules that were not taken into account by Leszek Kaczmarek in the 1980s.

The neural ELAVL protein HuB enhances endogenous proto-oncogene activation

“…Several reports demonstrated that E4 orf6 enhances the oncogenic effect of adenovirus E1A and E1B [12] [13]. As shown in Figure 4E, the numbers of transformed colonies that were transformed by E1 and HuB were significantly higher compared with E1-HuR [19]. It has been also reported that histon acetyltransferase (HAT) activity of CREBBP (CREB-binding protein), another ARE mRNA, is involved in memory consolidation [20].…”

Spike-timing-dependent plasticity rewards synchrony rather than causality

“…2A). As we could not record EPSPs and spikes in the incubator we used the immediate early gene cFos that is upregulated in burst-spiking neurons (Schoenenberger, Gerosa and Oertner, 2009) and in neurons that have undergone LTP (for review see Jaworski, Kalita and Knapska, 2018) as a surrogate. We found no cFos-positive ChrimsonR-CA3 neurons after causal pairing (9/9 slices) indicating that these neurons were not driven to burst by either the 630 nm light flashes (300 at 5 Hz, 8 mW mm −2 ) or the 405 nm flashes (300 bursts of 3 at 50 Hz, 12 ms delay, 1 mW mm −2 ).…”

Role of PPARs in Progression of Anxiety: Literature Analysis and Signaling Pathways Reconstruction

“…FOS gene is expressed in almost every tissue (https://www .ncbi.nlm.nih.gov/gene/2353). One of the most thorough research of this gene is focused on neuronal plasticity [51,52]. Animal models of anxiety, fear, and depression show increased FOS in the brain areas linked to the formation of these behavioral reactions in animals [53][54][55].…”