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| Photoreceptors and olfactory sensory neurons (OSNs). (A) Simplified schematic representation of a rod and a cone in the retina. Photoreceptors are polarized neurons with a specialized morphology optimized to detect light stimuli. The outer segments of both rods and cones are modified sensory cilia, containing membrane disks organized in a stack. In the case of rods, the outer segment has a slim rod-like structure in which the disks are enclosed by the plasma membrane. The outer segment of the cones has a stocky conical-shaped structure, in which the disks are constituted by invaginations of the plasma membrane. The outer segment does not contain any proteins of the cell translation machinery, which are mostly localized in the inner segment, including the endoplasmic reticulum, Golgi, and mitochondria. Outer and inner segments are connected by the connecting cilium, while distal to the inner segment is the cell body containing the nucleus, followed by the axon and synaptic termini that extend into the outer plexiform layer where they synapse with the second order neurons. When the light enters the eye, after reaching the retina, it travels along the length of the rod and cone inner segment until finally reaching the outer segments. (B) Simplified schematic of an OSNs in the olfactory epithelium. OSNs are ciliated bipolar neurons, their apical dendrites extend to the surface of the epithelium terminating with a spherical structure called dendritic knob, from which the sensory cilia enter the mucus layer. The ciliary membrane contains the olfactory receptors (ORs) necessary to detect different odorants. Distal from the knob is the cell body of the OSN with its nucleus, followed by a long axon that projects to the olfactory bulb, where it synapses with the second order neurons. Images created with BioRender.com.
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The past decades have seen tremendous progress in our understanding of the function of photoreceptors and olfactory sensory neurons, uncovering the mechanisms that determine their properties and, ultimately, our ability to see and smell. This progress has been driven to a large degree by the powerful combination of physiological experimental tools...
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Context 1
... rod and cone photoreceptors as well as OSNs are ciliary neurons (Figure 1) with specialized cilia where the initial detection of the sensory stimulus takes place to activate Simplified schematic representation of a rod and a cone in the retina. Photoreceptors are polarized neurons with a specialized morphology optimized to detect light stimuli. ...
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... sensory transduction cascade. Rods and cones have a single cilium that has evolved to accommodate a stack of ∼1,000 membrane disks where the visual pigment is expressed at a very high 3-5 mM concentration ( Figure 1A; Palczewski, 2006). In the case of rods, the disks are enveloped by the plasma membrane, whereas in cones the disks are formed by invaginations of the plasma membrane. ...
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... orientation of the elongated outer segments along the light path, together with the high density of visual pigment in their disks results in ∼50% probability that an incident photon is absorbed by a visual pigment molecule (Bowmaker and Dartnall, 1980). In the case of OSNs (Figure 1B), odorant ligands are detected in the ∼20 cilia protruding from each dendritic knob which are immersed in the mucus layer covering the olfactory epithelium. The olfactory cilia, which are motile in amphibians but not in rodents, are only about 0.1-0.2 ...
Citations
... Ethologically relevant odor-guided tasks, such as finding food, are crucial for animals to survive, failing to do so would cause death. Locating food based on its odor cues is dependent on a series of mechanisms starting at the very periphery of the olfactory system: odorant transduction mechanisms in olfactory sensory neurons (OSNs), which are located in the olfactory epithelium in the nasal cavity (Kleene, 2008;Tirindelli et al., 2009;Pifferi et al., 2012;Genovese et al., 2021). Inhaled odorants are detected by OSNs and are transduced first into a receptor current that then triggers action potentials that are conveyed to the olfactory bulb and secondary neurons (Cang and Isaacson, 2003;Spors et al., 2006;Gire et al., 2012;Tan et al., 2015). ...
Mammalian olfactory sensory neurons (OSNs) generate an odorant-induced response by sequentially activating two ion channels, which are in their ciliary membranes. First, a cationic, Ca ²⁺ -permeable cyclic nucleotide-gated channel is opened following odorant stimulation via a G protein-coupled transduction cascade and an ensuing raise in cAMP. Second, the increase in ciliary Ca ²⁺ opens the excitatory Ca ²⁺ -activated Cl- channel TMEM16B that carries most of the odorant-induced receptor current. While the role of TMEM16B in amplifying the response has been well established, it is less understood how this secondary ion channel contributes to response kinetics and action potential generation during single as well as repeated stimulation and, on the other hand, which response properties the CNG channel determines. We first demonstrate that basic membrane properties such as input resistance, resting potential and voltage-gated currents remained unchanged in OSNs that lack TMEM16B. The CNG channel predominantly determines the response delay and adaptation during odorant exposure, while the absence of the Cl- channels shortens both the time the response requires to reach its maximum as well as to terminate after odorant stimulation. This faster response termination in Tmem16b knockout OSNs allows them, somewhat counterintuitively, to fire action potentials more reliably when stimulated repeatedly in rapid succession, a phenomenon that occurs both in isolated OSNs as well as in OSNs within epithelial slices. Thus, while the two olfactory ion channels act in concert to generate the overall response, each one controls specific aspects of the odorant-induced response.
... that respond to stimuli and carry out transduction [3][4][5][6][7][8][9][10] . Energy-efficient and intelligent signal processing by the SNS has sparked extensive research efforts to mimic biological sensory neuronal systems, including receptors [11][12][13] . ...
The human olfactory system comprises olfactory receptor neurons, projection neurons, and interneurons that perform remarkably sophisticated functions, including sensing, filtration, memorization, and forgetting of chemical stimuli for perception. Developing an artificial olfactory system that can mimic these functions has proved to be challenging. Herein, inspired by the neuronal network inside the glomerulus of the olfactory bulb, we present an artificial chemosensory neuronal synapse that can sense chemical stimuli and mimic the functions of excitatory and inhibitory neurotransmitter release in the synapses between olfactory receptor neurons, projection neurons, and interneurons. The proposed device is based on a flexible organic electrochemical transistor gated by the potential generated by the interaction of gas molecules with ions in a chemoreceptive ionogel. The combined use of a chemoreceptive ionogel and an organic semiconductor channel allows for a long retentive memory in response to chemical stimuli. Long-term memorization of the excitatory chemical stimulus can be also erased by applying an inhibitory electrical stimulus due to ion dynamics in the chemoresponsive ionogel gate electrolyte. Applying a simple device design, we were able to mimic the excitatory and inhibitory synaptic functions of chemical synapses in the olfactory system, which can further advance the development of artificial neuronal systems for biomimetic chemosensory applications. Developing an artificial olfactory system that can mimic the biological functions remains a challenge. Here, the authors develop an artificial chemosensory synapse based on a flexible organic electrochemical transistor gated by the potential generated by the interaction of gas molecules with ions in a chemoreceptive ionogel.
... In physiology, sensory transduction is the transformation of a sensory stimulus into neuronal activity and involves a variety of different mechanisms. In olfaction, this is the transformation of chemical signals (odorants) into an electric one that is then transmitted to the brain (Genovese et al., 2021;Kleene, 2008;Pifferi et al., 2012;Tirindelli et al., 2009;Torre et al., 1995). ...
... The very first step in odor perception is the activation of the peripheral odorant transduction cascade that gives rise to the transduction current characterized by response amplitude and kinetics that must be tuned to the always-changing odorant landscape (Boccaccio et al., 2021;Genovese et al., 2021;Kleene, 2008). TMEM16B is the main Ca + -activated Cl¯ channel playing a role in odorant transduction. ...
The Ca 2+-activated Cl¯ channel TMEM16B carries up to 90% of the transduction current evoked by odorant stimulation in olfactory sensory neurons and control the number of action potential firing and therefore the length of the train of action potentials. A loss of function approach revealed that TMEM16B is required for olfactory-driven behaviors such as tracking unfamiliar odors. Here, we used the electro-olfactogram (EOG) technique to investigate the contribution of TMEM16B to odorant transduction in the whole olfactory epithelium. Surprisingly, we found that EOG responses from Tmem16b knock out mice have a bigger amplitude compared to those of wild type. Moreover, the kinetics of EOG responses is faster in absence of TMEM16B, while the ability to adapt to repeated stimulation is altered in knock out mice. The larger EOG responses in Tmem16b knock out may be the results of the removal of the clamping and/or shunting action of the Ca 2+-activated Cl¯ currents leading to the paradox of having smaller transduction current but larger generator potential.
... ONs are described as sharing "an amazing level of similarity" to photoreceptors in several aspects. In addition, the OR complexity compared to photoreceptors is evidenced by the use of five opsin genes to cover the visible spectrum, whereas ONs use hundreds of OR genes to cover the odor space [55]. The isolation of genes that code for olfactory receptors which showed they belonged to the class of Gprotein-coupled receptors led to the award of the 2004 Nobel Prize in Physiology or Medicine [56], exemplifying the importance of olfaction research in the scientific community. ...
A new hypothesis for the mechanism of olfaction is presented. It begins with an odorant molecule binding to an olfactory receptor. This is followed by the quantum biology event of inelastic electron tunneling as has been suggested with both the vibration and swipe card theories. It is novel in that it is not concerned with the possible effects of the tunneled electrons as has been discussed with the previous theories. Instead, the high energy state of the odorant molecule in the receptor following inelastic electron tunneling is considered. The hypothesis is that, as the high energy state decays, there is fluorescence luminescence with radiative emission of multiple photons. These photons pass through the supporting sustentacular cells and activate a set of olfactory neurons in near-simultaneous timing, which provides the temporal basis for the brain to interpret the required complex combinatorial coding as an odor. The Luminescence Hypothesis of Olfaction is the first to present the necessity of or mechanism for a 1:3 correspondence of odorant molecule to olfactory nerve activations. The mechanism provides for a consistent and reproducible time-based activation of sets of olfactory nerves correlated to an odor.The hypothesis has a biological precedent: an energy feasibility assessment is included, explaining the anosmia seen with COVID-19, and can be confirmed with existing laboratory techniques.
... Melanopsin (OPN4) is more ancient in terms of evolution than rod/cone opsins (Provencio et al., 2000) and engages different phototransduction cascades, resulting in cellular depolarization (for review, see Peirson and Foster, 2006). Thus, ipRGCs are very unusual photoreceptors; they are spiking neurons that depolarize in response to light, unlike rods and cones that are highly specialized neurons that respond to light with graded hyperpolarization (for review, see Genovese et al., 2021). Unlike rods and cones, which signal to the brain via second-and third-order retinal neurons, ipRGCs communicate light information to the brain directly, i.e. monosynaptically Hattar et al., 2002). ...
Developmental neuroscience research has not yet fully unveiled the dynamics involved in human birth. The trigger of the first breath, often assumed to be the marker of human life, has not been characterized nor has the process entailing brain modification and activation at birth been clarified yet. To date, few researchers only have investigated the impact of the extrauterine environment, with its strong stimuli, on birth. This ‘hypothesis and theory' article assumes the role of a specific stimulus activating the central nervous system (CNS) at human birth. This stimulus must have specific features though, such as novelty, efficacy, ubiquity, and immediacy. We propose light as a robust candidate for the CNS activation via the retina. Available data on fetal and neonatal neurodevelopment, in particular with reference to retinal light-responsive pathways, will be examined together with the GABA functional switch, and the subplate disappearance, which, at an experimental level, differentiate the neonatal brain from the fetal brain. In this study, we assume how a very rapid activation of retinal photoreceptors at birth initiates a sudden brain shift from the prenatal pattern of functions to the neonatal setup. Our assumption implies the presence of a photoreceptor capable of capturing and transducing light/photon stimulus, transforming it into an effective signal for the activation of new brain functions at birth. Opsin photoreception or, more specifically, melanopsin-dependent photoreception, which is provided by intrinsically photosensitive retinal ganglion cells (ipRGCs), is considered as a valid candidate. Although what is assumed herein cannot be verified in humans based on knowledge available so far, proposing an important and novel function can trigger a broad range of diversified research in different domains, from neurophysiology to neurology and psychiatry.
The article analyzes the literature data on the role of molecular olfactory receptors (OR) and cAMP in the formation of the topographic organization of the olfactory sensory system. Before its transmission to the brain, sensory information is already organized in the peripheral region according to the “one neuron–one receptor” principle, which also extends to the glomeruli in the olfactory bulb, which obey the “one glomerulus–one receptor” law. At present, an important role in the formation of the sensory map has been attributed to ORs, which plays a dual role in the organization of the olfactory system, since they are localized both in the olfactory cilia (OC) and in the membrane of the axon growth cone of the same olfactory sensory neuron (OSN), and determine the target for the axons of the OSN in the olfactory bulb (OB). However, there is strong evidence for the central role of the intracellular cAMP signaling system in sensory map development. Using the method of genetic mutation with the abolition of cAMP synthesis, it was revealed that the axons carrying this mutation never penetrate the glomerular layer, but remain in the layer of the olfactory nerve. At the same time, OSN axons target the OB but fail to form distinct and well-defined glomeruli, many of which become heterogeneous because they contain fibers belonging to OSNs expressing ORs for different odorants. Thus, cAMP synthesized in the tip of the RSN axon, under the action of signals from the OB, regulates the expression of molecules of its navigation to its target in the OB, and also forms intrabulbar chemical and electrical synapses, forming neuronal circuits. Numerous clinical and experimental data have led to the conclusion that the pathogenetic mechanisms of the development of some psychiatric diseases are associated with dysregulation of cAMP.
Both brown and white adipose tissues (BAT/WAT) are innervated by the peripheral nervous system, including efferent sympathetic nerves that communicate from the brain/central nervous system out to the tissue, and afferent sensory nerves that communicate from the tissue back to the brain and locally release neuropeptides to the tissue upon stimulation. This bidirectional neural communication is important for energy balance and metabolic control, as well as maintaining adipose tissue health through processes like browning (development of metabolically healthy brown adipocytes in WAT), thermogenesis, lipolysis, and adipogenesis. Decades of sensory nerve denervation studies have demonstrated the particular importance of adipose sensory nerves for brown adipose tissue and WAT functions, but far less is known about the tissue’s sensory innervation compared to the better-studied sympathetic nerves and their neurotransmitter norepinephrine. In this review, we cover what is known and not yet known about sensory nerve activities in adipose, focusing on their effector neuropeptide actions in the tissue.
Photoreceptor cells generate neuronal signals in response to capturing light. This process, called phototransduction, takes place in a highly specialized outer segment organelle. There are significant discrepancies in the reported amounts of many proteins supporting this process, particularly those of low abundance, which limits our understanding of their molecular organization and function. In this study, we used quantitative mass spectrometry to simultaneously determine the abundances of 20 key structural and functional proteins residing in mouse rod outer segments. We computed the absolute number of molecules of each protein residing within an individual outer segment and the molar ratio among all 20 proteins. The molar ratios of proteins comprising three well-characterized constitutive complexes in outer segments differed from the established subunit stoichiometries of these complexes by less than 7%, highlighting the exceptional precision of our quantification. Overall, this study resolves multiple existing discrepancies regarding the outer segment abundances of these proteins, thereby advancing our understanding of how the phototransduction pathway functions as a single, well-coordinated molecular ensemble.
