Can Dexmedetomidine Be Effective in the Protection of Radiotherapy-Induced Brain Damage in the Rat?

Approximately 7 million people are reported to be undergoing radiotherapy (RT) at any one time in the world. However, it is still not possible to prevent damage to secondary organs that are off-target. This study, therefore, investigated the potential adverse effects of RT on the brain, using cognitive, histopathological, and biochemical methods, and the counteractive effect of the α2-adrenergic receptor agonist dexmedetomidine. Thirty-two male Sprague Dawley rats aged 5-6 months were randomly allocated into four groups: untreated control, and RT, RT + dexmedetomidine-100, and RT + dexmedetomidine-200-treated groups. The passive avoidance test was applied to all groups. The RT groups received total body X-ray irradiation as a single dose of 8 Gy. The rats were sacrificed 24 h after X-ray irradiation, and following the application of the passive avoidance test. The brain tissues were subjected to histological and biochemical evaluation. No statistically significant difference was found between the control and RT groups in terms of passive avoidance outcomes and 8-hydroxy-2'- deoxyguanosine (8-OHdG) positivity. In contrast, a significant increase in tissue MDA and GSH levels and positivity for TUNEL, TNF-α, and nNOS was observed between the control and the irradiation groups (p < 0.05). A significant decrease in these values was observed in the groups receiving dexmedetomidine. Compared with the control group, gradual elevation was determined in GSH levels in the RT group, followed by the RT + dexmedetomidine-100 and RT + dexmedetomidine-200 groups. Dexmedetomidine may be beneficial in countering the adverse effects of RT in the cerebral and hippocampal regions.

Low light intensities increase avoidance behaviour of diurnal fish species: implications for use of road culverts by fish.

Inadequately designed culverts can be physical barriers to fish passage if they increase the velocity of water flow in the environment, alter natural turbulence patterns or fail to provide adequate water depth. They may also act as behavioural barriers to fish passage if they affect the willingness of fish species to enter or pass through the structure due to altered ambient light conditions. To understand how reduced light intensity might affect fish behaviour in culverts, the authors performed a behavioural choice experiment quantifying the amount of time individual fish spent in dark and illuminated areas of a controlled experimental channel. They found that behavioural responses were largely reflective of the species' diel activity patterns; the diurnal species Craterocephalus stercusmuscarum and Retropinna semoni preferred illuminated regions, whereas the nocturnal/crepuscular Macquaria novemaculeata preferred the darkened region of the channel. Bidyanus bidyanus were strongly rheotactic, and their behaviour was influenced more by water flow direction than ambient light level. The authors then determined that a threshold light intensity of only c. 100-200 lx (cf. midday sunlight c. 100,000 lx) was required to overcome the behavioural barrier in c. 70% of the diurnally active C. stercusmuscarum and R. semoni tested. When these values were placed into an environmental context, 15 road-crossing (3.4-7.0 m long) box (c. 1 m × 1 m, height × width) and pipe (c. 1 m diameter) culverts sampled in Brisbane, Australia, recorded light intensities in the centre of the structure that were below the threshold for C. stercusmuscarum and R. semoni movement and could potentially be a barrier to their passage through the structure. Attention is required to better understand the impacts of low light intensity in culverts on fish passage and to prioritize restoration.

Prenatal and early postnatal exposure to radiofrequency waves (900 MHz) adversely affects passive avoidance learning and memory.

Prenatal and early postnatal are the most sensitive and high-risk periods to expose to electromagnetic fields (EMFs). This study aimed to investigate the effect of prenatal and early postnatal exposure to 900 MHz radiofrequency waves (RFWs) emitted from a base transceiver station antenna on passive avoidance learning and memory (PALM) and hippocampus histomorphology. Female Sprague Dawley rats (190-230 g) were paired with males. The mated rats, confirmed by observing a vaginal plug, were divided into two groups; control and exposed. The control group (n = 7) was not exposed to RFW. The exposed group was divided into three subgroups (n = 8); exposed Ⅰ, exposed during the gestational period (fetal life), and exposed Ⅱ and Ⅲ (postnatal exposure), exposed to RFW during the first 21 days of life, for 2 h/d and 4 h/d, respectively. PALM was evaluated by a shuttle box in 45-day-old pups. Learning and memory of animals were demonstrated as the duration of remaining within the light area, which is called the lighting time. Histological sections were prepared from brain tissues and stained with hematoxylin and eosin. An impairment in the PALM performance was noticed in all exposed subgroups (Ⅰ, Ⅱ, and Ⅲ) (p < 0.05). Learning (short-term memory) and retention (long-term memory) behaviors were more affected in exposed subgroup Ⅰ (prenatal exposed) compared to other postnatal exposed subgroups (Ⅱ and Ⅲ). Also, a mild decrease in the density of pyramidal cells was observed in the hippocampus of exposed subgroups (Ⅰ and Ⅲ). Prenatal and early postnatal exposure to 900 MHz RFW adversely affected PALM performance and hippocampus tissue in rat pups with more impact for prenatal period exposure.

Circadian Regulation of Light-Evoked Attraction and Avoidance Behaviors in Daytime- versus Nighttime-Biting Mosquitoes.

Mosquitoes pose widespread threats to humans and other animals as disease vectors [1]. Day- versus night-biting mosquitoes occupy distinct time-of-day niches [2, 3]. Here, we explore day- versus night-biting female and male mosquitoes' innate temporal attraction/avoidance behavioral responses to light and their regulation by circadian circuit and molecular mechanisms. Day-biting mosquitoes Aedes aegypti, particularly females, are attracted to light during the day regardless of spectra. In contrast, night-biting mosquitoes, Anopheles coluzzii, specifically avoid ultraviolet (UV) and blue light during the day. Behavioral attraction to/avoidance of light in both species change with time of day and show distinct sex and circadian neural circuit differences. Males of both diurnal and nocturnal mosquito species show reduced UV light avoidance in anticipation of evening onset relative to females. The circadian neural circuits of diurnal/day- and nocturnal/night-biting mosquitoes based on PERIOD (PER) and pigment-dispersing factor (PDF) expression show similar but distinct circuit organizations between species. The basis of diurnal versus nocturnal behaviors is driven by molecular clock timing, which cycles in anti-phase between day- versus night-biting mosquitoes. Observed differences at the neural circuit and protein levels provide insight into the fundamental basis underlying diurnality versus nocturnality. Molecular disruption of the circadian clock severely interferes with light-evoked attraction/avoidance behaviors in mosquitoes. In summary, attraction/avoidance behaviors show marked differences between day- versus night-biting mosquitoes, but both classes of mosquitoes are circadian and light regulated, which may be applied toward species-specific control of harmful mosquitoes.

Approach Behavior Induced by 10.6-µm Laser Stimulation at Acupoint ST36 in a Rat Model of Incisional Pain.

Objective: Laser stimulation (LS) at both the injury site and specific acupoints may induce analgesic effects. The purpose of this study is to investigate the effects of LS at injury site or acupoint on analgesic-associated approach behavior and determine whether opioid receptors in the anterior cingulate cortex (ACC) were involved. Methods: The left hindpaw incision was established in rats. LS (10.6 µm) was performed at the ipsilateral (left) acupoint ST36 (Zusanli) or locally to the incision site. Characteristic guarding pain behavior was measured to assess incision-induced pain. A two-chamber conditioned place preference (CPP) paradigm was used to measure approach behavior induced by pain relief. To inhibit opioid receptors, naloxone was microinjected into the ACC before LS. Results: A delayed analgesic effect (24 h after treatment) was induced in both the LS groups (ST36 and incision site) as compared with the sham control or model groups (p < 0.05). An immediate (30 min after the end of the LS) decrease in guarding pain (p < 0.001) and CPP for the LS chamber (p < 0.001) were observed only in the ST36 LS group. The administration of naloxone in ACC inhibited the LS-induced analgesic effect and CPP (p < 0.05). Conclusions: Our results highlight the novel approach behavior of pain relief induced by 10.6-µm LS at ST36 in a rat model of incisional pain, and implicate ACC opioid receptor signaling in these actions.

Repeated exposure to nanosecond high power pulsed microwaves increases cancer incidence in rat.

High-power microwaves are used to inhibit electronics of threatening military or civilian vehicles. This work aims to assess health hazards of high-power microwaves and helps to define hazard threshold levels of modulated radiofrequency exposures such as those emitted by the first generations of mobile phones. Rats were exposed to the highest possible field levels, under single acute or repetitive exposures for eight weeks. Intense microwave electric fields at 1 MV m-1 of nanoseconds duration were applied from two sources at different carrier frequencies of 10 and 3.7 GHz. The repetition rate was 100 pps, and the duration of train pulses lasted from 10 s to twice 8 min. The effects on the central nervous system were evaluated, by labelling brain inflammation marker GFAP and by performing different behavioural tests: rotarod, T-maze, beam-walking, open-field, and avoidance test. Long-time survival was measured in animals repeatedly exposed, and anatomopathological analysis was performed on animals sacrificed at two years of life or earlier in case of precocious death. Control groups were sham exposed. Few effects were observed on behaviour. With acute exposure, an avoidance reflex was shown at very high thermal level (22 W kg-1); GFAP was increased some days after exposure. Most importantly, with repeated exposures, survival time was 4-months shorter in the exposed group, with eleven animals exhibiting a large sub-cutaneous tumour, compared to two in the sham group. A residual X-ray exposure was also present in the beam (0.8 Gy), which is probably not a bias for the observed result. High power microwaves below thermal level in average, can increase cancer prevalence and decrease survival time in rats, without clear effects on behaviour. The parameters of this effect need to be further explored, and a more precise dosimetry to be performed.

Photobiomodulation Using a Low-Level Light-Emitting Diode Improves Cognitive Dysfunction in the 5XFAD Mouse Model of Alzheimer's Disease.

Photobiomodulation using low-level light-emitting diode can be rapidly applied in neurological and physiological disorders safely and noninvasively. Photobiomodulation is effective for chronic diseases because of fewer side effects than drugs. Here we investigated the effects of photobiomodulation using light-emitting diode on amyloid plaques, gliosis, and neuronal loss to prevent and/or recover cognitive impairment, and optimal timing of photobiomodulation initiation for recovering cognitive function in a mouse model of Alzheimer's disease. 5XFAD mice were used as an Alzheimer's disease model. Animals receiving photobiomodulation treatment were divided into two groups: an early group starting photobiomodulation at 2 months of age (5XFAD+Early), and a late group starting photobiomodulation at 6 months of age (5XFAD+Delay). Both groups received photobiomodulation 20 minutes per session three times per week for 14 weeks. The Morris water maze, passive avoidance, and elevated plus maze tests were performed at 10 months of age. Immunohistochemistry and Western blot were performed after behavioral evaluation. The results showed that photobiomodulation treatment at early stages reduced amyloid accumulation, neuronal loss, and microgliosis and alleviated the cognitive dysfunction in 5XFAD mice, possibly by increasing insulin degrading enzyme related to amyloid-beta degradation. Photobiomodulation may be an excellent candidate for advanced preclinical Alzheimer's disease research.

Light Spot-Based Assay for Analysis of Drosophila Larval Phototaxis.

The larvae of Drosophila melanogaster show obvious light-avoiding behavior during the foraging stage. Drosophila larval phototaxis can be used as a model to study animal avoidance behavior. This protocol introduces a light-spot assay to investigate larval phototactic behavior. The experimental set-up includes two main parts: a visual stimulation system that generates the light spot, and an infrared light-based imaging system that records the process of larval light avoidance. This assay allows tracking of the behavior of larva before entering, during encountering, and after leaving the light spot. Details of larval movement including deceleration, pause, head casting, and turning can be captured and analyzed using this method.

Multiple Phototransduction Inputs Integrate to Mediate UV Light-evoked Avoidance/Attraction Behavior in Drosophila.

Short-wavelength light guides many behaviors that are crucial for an insect's survival. In Drosophila melanogaster, short-wavelength light induces both attraction and avoidance behaviors. How light cues evoke two opposite valences of behavioral responses remains unclear. Here, we comprehensively examine the effects of (1) light intensity, (2) timing of light (duration of exposure, circadian time of day), and (3) phototransduction mechanisms processing light information that determine avoidance versus attraction behavior assayed at high spatiotemporal resolution in Drosophila. External opsin-based photoreceptors signal for attraction behavior in response to low-intensity ultraviolet (UV) light. In contrast, the cell-autonomous neuronal photoreceptors, CRYPTOCHROME (CRY) and RHODOPSIN 7 (RH7), signal avoidance responses to high-intensity UV light. In addition to binary attraction versus avoidance behavioral responses to UV light, flies show distinct clock-dependent spatial preference within a light environment coded by different light input channels.

Circuits That Mediate Expression of Signaled Active Avoidance Converge in the Pedunculopontine Tegmentum.

An innocuous sensory stimulus that reliably signals an upcoming aversive event can be conditioned to elicit locomotion to a safe location before the aversive outcome ensues. The neural circuits that mediate the expression of this signaled locomotor action, known as signaled active avoidance, have not been identified. While exploring sensorimotor midbrain circuits in mice of either sex, we found that excitation of GABAergic cells in the substantia nigra pars reticulata blocks signaled active avoidance by inhibiting cells in the pedunculopontine tegmental nucleus (PPT), not by inhibiting cells in the superior colliculus or thalamus. Direct inhibition of putative-glutamatergic PPT cells, excitation of GABAergic PPT cells, or excitation of GABAergic afferents in PPT, abolish signaled active avoidance. Conversely, excitation of putative-glutamatergic PPT cells, or inhibition of GABAergic PPT cells, can be tuned to drive avoidance responses. The PPT is an essential junction for the expression of signaled active avoidance gated by nigral and other synaptic afferents.SIGNIFICANCE STATEMENT When a harmful situation is signaled by a sensory stimulus (e.g., street light), subjects typically learn to respond with active or passive avoidance responses that circumvent the threat. During signaled active avoidance behavior, subjects move away to avoid a threat signaled by a preceding innocuous stimulus. We identified a part of the midbrain essential to process the signal and avoid the threat. Inhibition of neurons in this area eliminates avoidance responses to the signal but preserves escape responses caused by presentation of the threat. The results highlight an essential part of the neural circuits that mediate signaled active avoidance behavior.

Physical activity as an option to reduce adverse effect of EMF exposure during pregnancy.

The popularity of using wireless fidelity over the last decades increased apprehensions about impact of high frequency electromagnetic fields (EMF) on health. Most of previous studies mentioned adverse effect of EMF on cognitive processes, but so far, no study has provided a way to control adverse effects of EMF exposure. The purpose of this study was to examine the effect of Wi-Fi EMF and physical activity on spatial learning and motor function in pregnant rat's offspring. Forty Albino-Wistar pregnant rats divided randomly into four groups (EMF, physical activity, combined 2.4GHZ EMF and physical activity and control groups). For assessing spatial learning in 56 post-natal days' old (PND) male offspring, Morris Water Maze (MWM) was used and to examine motor function Open-field test was taken. Although results of MWM test revealed that Wi-Fi modem EMF caused impairment in spatial learning in rats exposed to EMF but physical activity could reduce negative effect of EMF in pregnant rat's offspring who exposed during pregnancy but performed swimming. In addition, results of open-field test showed that litter's motor function in EMF group significantly declined in comparison with physical activity and combined 2.4GHZ EMF and physical activity groups. According to our findings, it can be concluded that execution physical activity individually or along with wave-exposed pregnancy can significantly progressive effect on offspring' cognitive and motor functions.

Exposure to GSM 900-MHz mobile radiation impaired inhibitory avoidance memory consolidation in rat: Involvements of opioidergic and nitrergic systems.

The use of mobile phones is increasing, and the main health concern is the possible deleterious effects of radiation on brain functioning. The present study aimed to examine the effects of exposure to a global system for mobile communication (GSM) with mobile phones on inhibitory avoidance (IA) memory performance as well as the involvement of endogenous opioids and nitric oxide (NO) in this task. Male Wistar rats, 10-12 weeks old, were used. The results showed that four weeks of mobile phone exposure impaired IA memory performance in rats. The results also revealed that post-training, but not pre-training, as well as pre-test intracerebroventricular (i.c.v.) injections of naloxone (0.4, 4 and 40 ng/rat), dose-dependently recovered the impairment of IA memory performance induced by GSM radiation. Additionally, the impairment of IA memory performance was completely recovered in the exposed animals with post-training treatment of naloxone (40 ng/rat) plus pre-test i.c.v. injections of L-arginine (100 and 200 nmol/rat). However, pre-test i.c.v. injections of L-NAME (10 and 20 nmol/rat), impaired IA memory performance in the animals receiving post-training naloxone (40 ng/rat). In the animals receiving post-training naloxone treatment, the impairment of IA memory performance due to pre-test i.c.v. injections of L-NAME was recovered by the pre-test co-administration of L-arginine. It was concluded that the recovery from impairment of IA memory in GSM-exposed animals with post-training naloxone treatment was the result of blockade of the opioidergic system in early memory consolidation as well as activation of the nitrergic system in the retrieval phase of memory.

Adult Neurogenesis Conserves Hippocampal Memory Capacity.

The hippocampus is crucial for declarative memories in humans and encodes episodic and spatial memories in animals. Memory coding strengthens synaptic efficacy via an LTP-like mechanism. Given that animals store memories of everyday experiences, the hippocampal circuit must have a mechanism that prevents saturation of overall synaptic weight for the preservation of learning capacity. LTD works to balance plasticity and prevent saturation. In addition, adult neurogenesis in the hippocampus is proposed to be involved in the down-scaling of synaptic efficacy. Here, we show that adult neurogenesis in male rats plays a crucial role in the maintenance of hippocampal capacity for memory (learning and/or memory formation). Neurogenesis regulated the maintenance of LTP, with decreases and increases in neurogenesis prolonging or shortening LTP persistence, respectively. Artificial saturation of hippocampal LTP impaired memory capacity in contextual fear conditioning, which completely recovered after 14 d, which was the time required for LTP to decay to the basal level. Memory capacity gradually recovered in parallel with neurogenesis-mediated gradual decay of LTP. Ablation of neurogenesis by x-ray irradiation delayed the recovery of memory capacity, whereas enhancement of neurogenesis using a running wheel sped up recovery. Therefore, one benefit of ongoing adult neurogenesis is the maintenance of hippocampal memory capacity through homeostatic renewing of hippocampal memory circuits. Decreased neurogenesis in aged animals may be responsible for the decline in cognitive function with age.SIGNIFICANCE STATEMENT Learning many events each day increases synaptic efficacy via LTP, which can prevent the storage of new memories in the hippocampal circuit. In this study, we demonstrate that hippocampal capacity for the storage of new memories is maintained by ongoing adult neurogenesis through homoeostatic renewing of hippocampal circuits in rats. A decrease or an increase in neurogenesis, respectively, delayed or sped up the recovery of memory capacity, suggesting that hippocampal adult neurogenesis plays a critical role in reducing LTP saturation and keeps the gate open for new memories by clearing out the old memories from the hippocampal memory circuit.

Light-Emitting Diode (LED) Therapy Attenuates Neurotoxicity of Methanol-Induced Memory Impairment and Apoptosis in The Hippocampus.

BACKGROUND & OBJECTIVE: The adolescent brain has a higher vulnerability to alcoholinduced neurotoxicity, compared to adult's brain. Most studies have investigated the effect of ethanol consumption on the body, however, methanol consumption, which peaked in the last years, is still poorly explored. METHOD: In this study, we investigated the effects of methanol neurotoxicity on memory function and pathological outcomes in the hippocampus of adolescent rats and examined the efficacy of Light- Emitting Diode (LED) therapy. Methanol induced neurotoxic rats showed a significant decrease in the latency period, in comparison to controls, which was significantly improved in LED treated rats at 7, 14 and 28 days, indicating recovery of memory function. In addition, methanol neurotoxicity in hippocampus caused a significant increase in cell death (caspase3+ cells) and cell edema at 7 and 28 days, which were significantly decreased by LED therapy. Furthermore, the number of glial fibrillary acid protein astrocytes was significantly lower in methanol rats, compared to controls, whereas LED treatment caused their significant increase. Finally, methanol neurotoxicity caused a significant decrease in the number of brain-derived neurotrophic factor (BDNF+) cells, but also circulating serum BDNF, at 7 and 28 days, compared to controls, which were significantly increased by LED therapy. Importantly, LED significantly increased the number of Ki-67+ cells and BDNF levels in the serum and hypothalamus in control-LED rats, compared to controls without LED therapy. CONCLUSION: In conclusion, chronic methanol administration caused severe memory impairments and several pathological outcomes in the hippocampus of adolescent rats which were improved by LED therapy.

Photons and foraging: Artificial light at night generates avoidance behaviour in male, but not female, New Zealand weta.

Avoiding foraging under increased predation risk is a common anti-predator behaviour. Using artificial light to amplify predation risk at ecologically valuable sites has been proposed to deter introduced mice (Mus musculus) and ship rats (Rattus rattus) from degrading biodiversity in island ecosystems. However, light may adversely affect native species; in particular, little is known about invertebrate responses to altered lighting regimes. We investigated how endemic orthopterans responded to artificial light at Maungatautari Ecological Island (Waikato, New Zealand). We predicted that based on their nocturnal behaviour, ecology and evolutionary history, tree weta (Hemideina thoracica) and cave weta (Rhaphidophoridae) would reduce their activity under illumination. Experimental stations (n = 15) experienced three evenings under each treatment (order randomised): (a) light (illuminated LED fixture), (b) dark (unilluminated LED fixture) and (c) baseline (no lighting fixture). Weta visitation rates were analysed from images captured on infra-red trail cameras set up at each station. Light significantly reduced the number of observations of cave (71.7% reduction) and tree weta (87.5% reduction). In observations where sex was distinguishable (53% of all visits), male tree weta were observed significantly more often (85% of visits) than females (15% of visits) and while males avoided illuminated sites, no detectable difference was observed across treatments for females. Sex could not be distinguished for cave weta. Our findings have implications for the use of light as a novel pest management strategy, and for the conservation of invertebrate diversity and abundance within natural and urban ecosystems worldwide that may be affected by light pollution.

Combined effects of antiorthostatic suspension and ionizing radiation on the behaviour and neurotransmitters changes in different brain structures of rats.

Space flight factors (SFF) significantly affect the operating activity of astronauts during deep space missions. In contrast to an orbital flight, leaving the Earth's magnetic field is fraught with the dangers of exposure to ionizing radiation and more specifically, the high-energy nuclei component of galactic cosmic rays. Microgravity, just another critical non-radiation factor, significantly affects the normal functioning of the CNS. Some morphological structures of the brain, such as the prefrontal cortex and the hippocampus, that are rich in monoaminergic and acetylcholinergic neurones, are the most sensitive to the effects of ionizing radiation and non-radiation spaceflight factors (SFF). In this work we have studied the combined effects of microgravity (in antiorthostatic suspension model, AS) and irradiation (γ-ray and protons in spread-out Bragg peak) on the behaviour, cognitive abilities, and metabolism of monoamines and acetylcholine in the key structures of the rat's brain. Irradiation (as independently as combined with AS) resulted in the decrease of thigmotaxis in rats. Learning problems, caused by the malfunctioning of the working memory but not the spatial memory, were observed in response to AS as well as to the SFF in combination. Analysis of monoamines metabolism showed that the serotoninergic system was the most affected by the SFF. Concentration of acetylcholine in the hippocampus significantly increased in the groups of irradiated rats, and in the groups which were exposed to the SFF in combination, compared to the rats exposed only to AS.

Structural foundations of optogenetics: Determinants of channelrhodopsin ion selectivity.

The structure-guided design of chloride-conducting channelrhodopsins has illuminated mechanisms underlying ion selectivity of this remarkable family of light-activated ion channels. The first generation of chloride-conducting channelrhodopsins, guided in part by development of a structure-informed electrostatic model for pore selectivity, included both the introduction of amino acids with positively charged side chains into the ion conduction pathway and the removal of residues hypothesized to support negatively charged binding sites for cations. Engineered channels indeed became chloride selective, reversing near -65 mV and enabling a new kind of optogenetic inhibition; however, these first-generation chloride-conducting channels displayed small photocurrents and were not tested for optogenetic inhibition of behavior. Here we report the validation and further development of the channelrhodopsin pore model via crystal structure-guided engineering of next-generation light-activated chloride channels (iC++) and a bistable variant (SwiChR++) with net photocurrents increased more than 15-fold under physiological conditions, reversal potential further decreased by another ∼ 15 mV, inhibition of spiking faithfully tracking chloride gradients and intrinsic cell properties, strong expression in vivo, and the initial microbial opsin channel-inhibitor-based control of freely moving behavior. We further show that inhibition by light-gated chloride channels is mediated mainly by shunting effects, which exert optogenetic control much more efficiently than the hyperpolarization induced by light-activated chloride pumps. The design and functional features of these next-generation chloride-conducting channelrhodopsins provide both chronic and acute timescale tools for reversible optogenetic inhibition, confirm fundamental predictions of the ion selectivity model, and further elucidate electrostatic and steric structure-function relationships of the light-gated pore.

Sweet and bitter taste in the brain of awake behaving animals.

Taste is responsible for evaluating the nutritious content of food, guiding essential appetitive behaviours, preventing the ingestion of toxic substances, and helping to ensure the maintenance of a healthy diet. Sweet and bitter are two of the most salient sensory percepts for humans and other animals; sweet taste allows the identification of energy-rich nutrients whereas bitter warns against the intake of potentially noxious chemicals. In mammals, information from taste receptor cells in the tongue is transmitted through multiple neural stations to the primary gustatory cortex in the brain. Recent imaging studies have shown that sweet and bitter are represented in the primary gustatory cortex by neurons organized in a spatial map, with each taste quality encoded by distinct cortical fields. Here we demonstrate that by manipulating the brain fields representing sweet and bitter taste we directly control an animal's internal representation, sensory perception, and behavioural actions. These results substantiate the segregation of taste qualities in the cortex, expose the innate nature of appetitive and aversive taste responses, and illustrate the ability of gustatory cortex to recapitulate complex behaviours in the absence of sensory input.

Dual Color Neural Activation and Behavior Control with Chrimson and CoChR in Caenorhabditis elegans.

By enabling a tight control of cell excitation, optogenetics is a powerful approach to study the function of neurons and neural circuits. With its transparent body, a fully mapped nervous system, easily quantifiable behaviors and many available genetic tools, Caenorhabditis elegans is an extremely well-suited model to decipher the functioning logic of the nervous system with optogenetics. Our goal was to establish an efficient dual color optogenetic system for the independent excitation of different neurons in C. elegans. We combined two recently discovered channelrhodopsins: the red-light sensitive Chrimson from Chlamydomonas noctigama and the blue-light sensitive CoChR from Chloromonas oogama. Codon-optimized versions of Chrimson and CoChR were designed for C. elegans and expressed in different mechanosensory neurons. Freely moving animals produced robust behavioral responses to light stimuli of specific wavelengths. Since CoChR was five times more sensitive to blue light than the commonly used ChR2, we were able to use low blue light intensities producing no cross-activation of Chrimson. Thanks to these optogenetics tools, we revealed asymmetric cross-habituation effects between the gentle and harsh touch sensory motor pathways. Collectively, our results establish the Chrimson/CoChR pair as a potent tool for bimodal neural excitation in C. elegans and equip this genetic model organism for the next generation of in vivo optogenetic analyses.

Mushroom body output neurons encode valence and guide memory-based action selection in Drosophila.

Animals discriminate stimuli, learn their predictive value and use this knowledge to modify their behavior. In Drosophila, the mushroom body (MB) plays a key role in these processes. Sensory stimuli are sparsely represented by ∼2000 Kenyon cells, which converge onto 34 output neurons (MBONs) of 21 types. We studied the role of MBONs in several associative learning tasks and in sleep regulation, revealing the extent to which information flow is segregated into distinct channels and suggesting possible roles for the multi-layered MBON network. We also show that optogenetic activation of MBONs can, depending on cell type, induce repulsion or attraction in flies. The behavioral effects of MBON perturbation are combinatorial, suggesting that the MBON ensemble collectively represents valence. We propose that local, stimulus-specific dopaminergic modulation selectively alters the balance within the MBON network for those stimuli. Our results suggest that valence encoded by the MBON ensemble biases memory-based action selection.