Single-photon optogenetics enables precise, cell-type-specific modulation of neuronal circuits, making it a crucial tool in neuroscience. Its miniaturization in the form of fully implantable wide-field stimulator arrays enables long-term interrogation of cortical circuits and bears promise for brain-machine interfaces for sensory and motor function restoration. However, achieving selective activation of functional cortical representations poses a challenge, as studies show that targeted optogenetic stimulation results in activity spread beyond one functional domain. While recurrent network mechanisms contribute to activity spread, here we demonstrate with detailed simulations of isolated pyramidal neurons from cats of unknown sex that already neuron morphology causes a complex spread of optogenetic activity at the scale of one cortical column. Since the shape of a neuron impacts its optogenetic response, we find that a single stimulator at the cortical surface recruits a complex spatial distribution of neurons that can be inhomogeneous and vary with stimulation intensity and neuronal morphology across layers. We explore strategies to enhance stimulation precision, finding that optimizing stimulator optics may offer more significant improvements than the preferentially somatic expression of the opsin through genetic targeting. Our results indicate that, with the right optical setup, single-photon optogenetics can precisely activate isolated neurons at the scale of functional cortical domains spanning several hundred micrometers.
- MeSH
- Cats MeSH
- Models, Neurological MeSH
- Cerebral Cortex physiology cytology MeSH
- Neurons physiology MeSH
- Optogenetics * methods MeSH
- Pyramidal Cells physiology MeSH
- Photic Stimulation methods MeSH
- Animals MeSH
- Check Tag
- Cats MeSH
- Male MeSH
- Female MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- MeSH
- Brain * physiology MeSH
- Mice MeSH
- Neurons physiology MeSH
- Optogenetics * methods MeSH
- Mammals MeSH
- Check Tag
- Mice MeSH
Cíl: Práce seznamuje čtenáře s inovativními postupy v léčbě sítnicových one-mocnění, které by se mohly v následujících letech dostat do klinické praxe. Po-psány jsou retinální protézy, transplantace retinálního pigmentového epitelu (RPE), genová terapie a optogenetika.Metodika: Literární rešerše zaměřená na charakteristiky a mechanismy jednotlivých druhů terapií. Výsledky: Retinální protézy, transplantace RPE, genová terapie a optogenetika nabízejí dosud plně neprobádané možnosti a jsou považovány za budoucnost léčby sítnicových onemocnění tam, kde klasická farmakoterapie či chirurgické možnosti léčby nestačí. Nicméně všechny tyto metody jsou výzvou nejen pro samotné inovativní technické provedení, ale také pro etickou, administrativní a ekonomickou náročnost. Závěr: V léčbě sítnicových onemocnění nás čeká zajímavá budoucnost a nelze nyní odhadnout, která modalita léčby bude dominantní.
Objective: The aim of this comprehensive paper is to acquaint the readers with innovative approaches in the treatment of retinal diseases, which could in the coming years to get into clinical practice. Retinal prostheses, retinal pigment epithelial (RPE) transplantation, gene therapy and optogenetics will be described in this paper. Methodology: Describing the basic characteristics and mechanisms of different types of therapy and subsequently literary minireview clarifying the current state of knowledge in the area. Results: Retinal prostheses, RPE transplantation, gene therapy and optogenetics offer yet unexplored possibilities and are considered as the future of treatment of retinal diseases where classical pharmacotherapy or surgical treatment are no longer sufficient. However, all these methods challenge not only in the innovative technical implementation itself, but also for the ethical, administrative and economic demands. Conclusion: There will be certainly interesting development in the treatment of retinal diseases, but it is not possible to fully estimate which modality of treatment will be dominant in the future.
- Keywords
- retinální protézy,
- MeSH
- Cell- and Tissue-Based Therapy methods trends MeSH
- Implants, Experimental MeSH
- Genetic Therapy methods trends MeSH
- Genetic Vectors MeSH
- Induced Pluripotent Stem Cells MeSH
- Clinical Studies as Topic MeSH
- Humans MeSH
- Retinal Diseases * therapy MeSH
- Ophthalmologic Surgical Procedures methods MeSH
- Optogenetics methods trends MeSH
- Retinal Pigment Epithelium MeSH
- Stem Cell Transplantation methods MeSH
- Check Tag
- Humans MeSH
- Publication type
- Review MeSH
Generation of an electrochemical proton gradient is the first step of cell bioenergetics. In prokaryotes, the gradient is created by outward membrane protein proton pumps. Inward plasma membrane native proton pumps are yet unknown. We describe comprehensive functional studies of the representatives of the yet noncharacterized xenorhodopsins from Nanohaloarchaea family of microbial rhodopsins. They are inward proton pumps as we demonstrate in model membrane systems, Escherichia coli cells, human embryonic kidney cells, neuroblastoma cells, and rat hippocampal neuronal cells. We also solved the structure of a xenorhodopsin from the nanohalosarchaeon Nanosalina (NsXeR) and suggest a mechanism of inward proton pumping. We demonstrate that the NsXeR is a powerful pump, which is able to elicit action potentials in rat hippocampal neuronal cells up to their maximal intrinsic firing frequency. Hence, inwardly directed proton pumps are suitable for light-induced remote control of neurons, and they are an alternative to the well-known cation-selective channelrhodopsins.
- MeSH
- Archaea metabolism MeSH
- Cell Line MeSH
- Escherichia coli metabolism MeSH
- Hydrogen-Ion Concentration MeSH
- Protein Conformation MeSH
- Humans MeSH
- Liposomes MeSH
- Models, Molecular MeSH
- Optogenetics * methods MeSH
- Proton Pumps metabolism MeSH
- Protons MeSH
- Retina metabolism MeSH
- Rhodopsin chemistry metabolism MeSH
- Spectrum Analysis MeSH
- Light MeSH
- Protein Binding MeSH
- Binding Sites MeSH
- Chromatography, High Pressure Liquid MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
