The behavioral relevance of a modular organization in the lateral habenula.

Behavioral strategies for survival rely on the updates the brain continuously makes based on the surrounding environment. External stimuli-neutral, positive, and negative-relay core information to the brain, where a complex anatomical network rapidly organizes actions, including approach or escape, and regulates emotions. Human neuroimaging and physiology in nonhuman primates, rodents, and teleosts suggest a pivotal role of the lateral habenula in translating external information into survival behaviors. Here, we review the literature describing how discrete habenular modules-reflecting the molecular signatures, anatomical connectivity, and functional components-are recruited by environmental stimuli and cooperate to prompt specific behavioral outcomes. We argue that integration of these findings in the context of valence processing for reinforcing or discouraging behaviors is necessary, offering a compelling model to guide future work.

Long-Lasting and Responsive DNA/Enzyme-Based Programs in Serum-Supplemented Extracellular Media.

DNA molecular programs are emerging as promising pharmaceutical approaches due to their versatility for biomolecular sensing and actuation. However, the implementation of DNA programs has been mainly limited to serum-deprived in vitro assays due to the fast deterioration of the DNA reaction networks by the nucleases present in the serum. Here, we show that DNA/enzyme programs are functional in serum for 24 h but are later disrupted by nucleases that give rise to parasitic amplification. To overcome this, we implement three-letter code networks that suppress autocatalytic parasites while still conserving the functionality of DNA/enzyme programs for at least 3 days in the presence of 10% serum. In addition, we define a new buffer that further increases the biocompatibility and conserves responsiveness to changes in molecular composition across time. Finally, we demonstrate how serum-supplemented extracellular DNA molecular programs remain responsive to molecular inputs in the presence of living cells, having responses 6-fold faster than the cellular division rate, and are sustainable for at least three cellular divisions. This demonstrates the possibility of implementing in situ biomolecular characterization tools for serum-demanding in vitro models. We foresee that the coupling of chemical reactivity to our DNA programs by aptamers or oligonucleotide conjugations will allow the implementation of extracellular synthetic biology tools, which will offer new biomolecular pharmaceutical approaches and the emergence of complex and autonomous in vitro models.

On the Generation and Regeneration of Retinal Ganglion Cells.

Retinal development follows a conserved neurogenic program in vertebrates to orchestrate the generation of specific cell types from multipotent progenitors in sequential but overlapping waves. In this program, retinal ganglion cells (RGCs) are the first cell type generated. RGCs are the final output neurons of the retina and are essential for vision and circadian rhythm. Key molecular steps have been defined in multiple vertebrate species to regulate competence, specification, and terminal differentiation of this cell type. This involves neuronal-specific transcription factor networks, regulators of chromatin dynamics and miRNAs. In mammals, RGCs and their optic nerve axons undergo neurodegeneration and loss in glaucoma and other optic neuropathies, resulting in irreversible vision loss. The incapacity of RGCs and axons to regenerate reinforces the need for the design of efficient RGC replacement strategies. Here we describe the essential molecular pathways for the differentiation of RGCs in vertebrates, as well as experimental manipulations that extend the competence window for generation of this early cell type from late progenitors. We discuss recent advances in regeneration of retinal neurons in vivo in both mouse and zebrafish and discuss possible strategies and barriers to achieving RGC regeneration as a therapeutic approach for vision restoration in blinding diseases such as glaucoma.