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1.
Sci Adv ; 10(13): eadh9251, 2024 Mar 29.
Article in English | MEDLINE | ID: mdl-38552022

ABSTRACT

The ventromedial prefrontal cortex (vmPFC) is a part of the limbic system engaged in the regulation of social, emotional, and cognitive states, which are characteristically impaired in disorders of the brain such as schizophrenia and depression. Here, we show that intrinsically photosensitive retinal ganglion cells (ipRGCs) modulate, through light, the integrity, activity, and function of the vmPFC. This regulatory role, which is independent of circadian and mood alterations, is mediated by an ipRGC-thalamic-corticolimbic pathway. Lack of ipRGC signaling in mice causes dendritic degeneration, dysregulation of genes involved in synaptic plasticity, and depressed neuronal activity in the vmPFC. These alterations primarily undermine the ability of the vmPFC to regulate emotions. Our discovery provides a potential light-dependent mechanism for certain PFC-centric disorders in humans.


Subject(s)
Brain , Retinal Ganglion Cells , Humans , Mice , Animals , Retinal Ganglion Cells/metabolism , Prefrontal Cortex , Signal Transduction , Light
2.
bioRxiv ; 2023 Dec 13.
Article in English | MEDLINE | ID: mdl-37808740

ABSTRACT

This manuscript has been withdrawn by bioRxiv following a formal request by the NIH Intramural Research Integrity Office owing to lack of author consent.

3.
Cell ; 175(1): 71-84.e18, 2018 09 20.
Article in English | MEDLINE | ID: mdl-30173913

ABSTRACT

Light exerts a range of powerful biological effects beyond image vision, including mood and learning regulation. While the source of photic information affecting mood and cognitive functions is well established, viz. intrinsically photosensitive retinal ganglion cells (ipRGCs), the central mediators are unknown. Here, we reveal that the direct effects of light on learning and mood utilize distinct ipRGC output streams. ipRGCs that project to the suprachiasmatic nucleus (SCN) mediate the effects of light on learning, independently of the SCN's pacemaker function. Mood regulation by light, on the other hand, requires an SCN-independent pathway linking ipRGCs to a previously unrecognized thalamic region, termed perihabenular nucleus (PHb). The PHb is integrated in a distinctive circuitry with mood-regulating centers and is both necessary and sufficient for driving the effects of light on affective behavior. Together, these results provide new insights into the neural basis required for light to influence mood and learning.


Subject(s)
Affect/radiation effects , Learning/radiation effects , Light , Affect/physiology , Animals , Brain/physiology , Circadian Rhythm , Learning/physiology , Mice , Mice, Inbred C57BL , Phototherapy/methods , Retina/metabolism , Retina/physiology , Retinal Ganglion Cells/metabolism , Retinal Ganglion Cells/physiology , Retinal Ganglion Cells/radiation effects , Signal Transduction/physiology , Suprachiasmatic Nucleus/metabolism , Vision, Ocular/physiology , Visual Pathways/metabolism , Visual Perception/physiology
4.
Annu Rev Neurosci ; 40: 539-556, 2017 07 25.
Article in English | MEDLINE | ID: mdl-28525301

ABSTRACT

The discovery of a third type of photoreceptors in the mammalian retina, intrinsically photosensitive retinal ganglion cells (ipRGCs), has had a revolutionary impact on chronobiology. We can now properly account for numerous non-vision-related functions of light, including its effect on the circadian system. Here, we give an overview of ipRGCs and their function as it relates specifically to mood and biological rhythms. Although circadian disruptions have been traditionally hypothesized to be the mediators of light's effects on mood, here we present an alternative model that dispenses with assumptions of causality between the two phenomena and explains mood regulation by light via another ipRGC-dependent mechanism.


Subject(s)
Affect/physiology , Circadian Rhythm/physiology , Photoreceptor Cells/metabolism , Retinal Ganglion Cells/metabolism , Rod Opsins/metabolism , Animals , Photoperiod
6.
BMC Bioinformatics ; 13 Suppl 4: S9, 2012 Mar 28.
Article in English | MEDLINE | ID: mdl-22536976

ABSTRACT

BACKGROUND: The process of solutes entrapment during liposomes formation is interesting for the investigation of the relationship between the formation of compartments and the distribution of molecules inside them; a relevant issue in the studies of the origin of life. Theoretically, when no interactions are supposed among the chemical species to be entrapped, the entrapment is described by a standard Poisson process. But very recent experimental findings show that, for small liposomes (100 nm diameter), the distribution of entrapped molecules is best described by a power-law function. This is of a great importance, as the two random processes give rise to two completely different scenarios. Here we present an in silico stochastic simulation of the encapsulation of a cell-free molecular translation system (the PURE system), obtained following two different entrapment models: a pure Poisson process, and a power-law. The protein synthesis inside the liposomes has been studied in both cases, with the aim to highlight experimental observables that could be measured to assess which model gives a better representation of the real process. RESULTS: Firstly, a minimal model for in vitro protein synthesis, based on the PURE system molecular composition, has been formalized. Then, we have designed a reliable experimental simulation where stochastic factors affect the reaction course inside the compartment. To this end, 24 solutes, which represent the PURE system components, have been stochastically distributed among vesicles by following either a Poisson or a power-law distribution. The course of the protein synthesis within each vesicle has been consequently calculated, as a function of vesicle size. Our study can predict translation yield in a population of small liposomes down to the attoliter (10(-18) L) range. Our results show that the efficiency of protein synthesis peaks at approximately 3 · 10(-16) L (840 nm diam.) with a Poisson distribution of solutes, while a relative optimum is found at around 10(-17) L (275 nm diam.) for the power-law statistics. CONCLUSIONS: Our simulation clearly shows that the wet-lab measurement of an effective protein synthesis at smaller volumes than 10(-17) L would rule out, according to our models, a Poisson distribution of solutes.


Subject(s)
Artificial Cells/chemistry , Escherichia coli/metabolism , Liposomes/metabolism , Protein Biosynthesis , Kinetics , Liposomes/chemistry , Metabolic Networks and Pathways
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