Neuronal Activity In Response Research Articles

Implantable acousto-optic window for monitoring ultrasound-mediated neuromodulation in vivo.

.SignificanceUltrasound has recently received considerable attention in neuroscience because it provides noninvasive control of deep brain activity. Although the feasibility of ultrasound stimulation has been reported in preclinical and clinical settings, its mechanistic understanding remains limited. While optical microscopy has become the “gold standard” tool for investigating population-level neural functions in vivo, its application for ultrasound neuromodulation has been technically challenging, as most conventional ultrasonic transducers are not designed to be compatible with optical microscopy.AimWe aimed to develop a transparent acoustic transducer based on a glass coverslip called the acousto-optic window (AOW), which simultaneously provides ultrasound neuromodulation and microscopic monitoring of neural responses in vivo.ApproachThe AOW was fabricated by the serial deposition of transparent acoustic stacks on a circular glass coverslip, comprising a piezoelectric material, polyvinylidene fluoride-trifluoroethylene, and indium-tin-oxide electrodes. The fabricated AOW was implanted into a transgenic neural-activity reporter mouse after open craniotomy. Two-photon microscopy was used to observe neuronal activity in response to ultrasonic stimulation through the AOW.ResultsThe AOW allowed microscopic imaging of calcium activity in cortical neurons in response to ultrasound stimulation. The optical transparency was over the visible and near-infrared spectra, and the ultrasonic pressure was 0.035 MPa at 10 MHz corresponding to . In anesthetized Gad2-GCaMP6-tdTomato mice, we observed robust ultrasound-evoked activation of inhibitory cortical neurons at depths up to .ConclusionsThe AOW is an implantable ultrasonic transducer that is broadly compatible with optical imaging modalities. The AOW will facilitate our understanding of ultrasound neuromodulation in vivo.

Inverse Neurovascular Coupling Contributes to Vasopressin Neuronal Activation in Response to Systemic Homeostatic Challenge

Neurovascular coupling (NVC), the process that links neuronal activity to cerebral blood flow changes, has been mainly studied in superficial brain areas, namely the neocortex. Still, whether the conventional, rapid and spatially restricted NVC response can be generalized to deeper, and functionally diverse brain regions remains unknown. The hypothalamic supraoptic nucleus (SON) is a deep brain region with unique cytoarchitectural properties including a high vascularization. Paradoxically, the dense vascular network is not required to maintain its metabolic demand. This mismatch in metabolic supply and demand suggests that the SON vasculature may serve additional functions beyond the delivery of energy substrates. To address this important gap in our knowledge, we set up the objective to implement a novel experimental approach to enable in vivo, real‐time two‐photon imaging from the ventral surface of the brain to monitor SON NVC responses to a systemic homeostatic challenge. Using this approach in anaesthetized male and female transgenic rats expressing GFP driven by the vasopressin (VP) promoter (VP‐GFP rats), we found that a systemic hypertonic saline (HTS) infusion evoked a gradual and linear increase in the firing rate of VP neurons (p < 0.0001; n = 4). Rather than resulting in a classical vasodilatory NVC, the increased VP neuronal activity was accompanied by a significant intraparenchymal arteriole (but not venule) vasoconstriction (one‐way RM ANOVA; p < 0.0001; n = 13 vessels from 5 rats). This “inverse” NVC was prevented when a VP V1a receptor antagonist was locally delivered within the SON (one‐way RM ANOVA; p < 0.0001; n = 4 vessels from 4 rats). The HTS infusion also significantly decreased RBC velocity in SON capillaries (one‐way RM ANOVA; p < 0.0001; n = 17 vessels from 6 rats) indicative of a decreased SON blood flow. The salt‐induced inverse NVC response resulted in a rapid and progressive decrease in SON pO2 (one‐way RM ANOVA; p < 0.002; n = 6 rats), along with an increased expression of the hypoxia inducible factor (HIF)‐1a mRNA (p < 0.001; one‐sample t test n = 6 rats). Finally, we show that a hypoxic SON microenvironment significantly increased the firing activity of VP neurons in ex vivo slices (p < 0.02; paired t test; n = 14 cells from 10 rats). Taken together, we show that the salt‐induced inverse NVC in the SON results in a hypoxia‐mediated positive feedback mechanism, which we propose contributes to sustain the activity of VP neurons in response to a systemic homeostatic challenge.

Astrocytic BDNF signaling within the ventromedial hypothalamus regulates energy homeostasis.

Brain-derived neurotrophic factor (BDNF) is essential for maintaining energy and glucose balance within the central nervous system. Because the study of its metabolic actions has been limited to effects in neuronal cells, its role in other cell types within the brain remains poorly understood. Here we show that astrocytic BDNF signaling within the ventromedial hypothalamus (VMH) modulates neuronal activity in response to changes in energy status. This occurs via the truncated TrkB.T1 receptor. Accordingly, either fasting or central BDNF depletion enhances astrocytic synaptic glutamate clearance, thereby decreasing neuronal activity in mice. Notably, selective depletion of TrkB.T1 in VMH astrocytes blunts the effects of energy status on excitatory transmission, as well as on responses to leptin, glucose and lipids. These effects are driven by increased astrocytic invasion of excitatory synapses, enhanced glutamate reuptake and decreased neuronal activity. We thus identify BDNF/TrkB.T1 signaling in VMH astrocytes as an essential mechanism that participates in energy and glucose homeostasis.

Characterizing the transcriptionally‐activated ensembles recruited by cocaine in the nucleus accumbens

While significant effort has been made to understand the neural basis of addiction, it remains unclear exactly how the brain controls motivated behaviors and how drugs of abuse alter these neural systems to control drug taking and seeking. The goal of this study was to understand how cocaine and associated stimuli are encoded in the brain and how neuronal activation in response to cocaine acts to drive drug seeking. In a given brain region, only a small percentage of cells are activated to any stimulus ‐ termed an “ensemble”. Here we aimed to determine if ensembles transcriptionally activated by cocaine in the nucleus accumbens (NAc) – a brain region central to reward encoding ‐ were capable of driving motivated behaviors in isolation. Using transgenic animals that allowed for the temporally specific tagging of ensembles with optical tools, we were able to record from, identify, and manipulate the neural ensembles that are selectively activated by cocaine experience. Using conditional viruses in combination with these transgenic mice, we expressed opsins in cocaine‐ or saline‐ (for control) activated neuronal ensembles within the NAc. A fiberoptic was placed above the region and animals performed operant conditioning tasks where a nosepoke triggered a laser pulse that would reactivate or inhibit cocaine‐activated ensembles to determine their role in motivated behaviors. Mice were highly motivated to optically reactivate the ensembles that were activated by the first cocaine experience, highlighted by their high rates of responding for reactivation. Repeated cocaine injections in these animals did not change the reinforcing efficacy of ensemble activation, suggesting that the increases in motivated behavior that occur following repeated cocaine exposure may be due to the recruitment of a novel ensemble. Indeed, via immunohistochemistry, we find minimal overlap between the neurons activated by the first cocaine experience and the tenth. Using a similar approach as described above, we conditionally deleted the cocaine‐ or saline‐activated ensembles using a diphtheria toxin and had the mice perform cocaine self‐administration to assess changes in acquisition, performance, or intake of cocaine. We observed no changes in cocaine self‐administration behavior, suggesting that, while the cocaine ensemble is sufficient for reinforcing motivated behavior, it is not necessary for reinforcement learning about cocaine or cocaine‐associated cues. We also show that repeated cocaine exposure recruits a new population of neurons to guide behavior. Overall, we hypothesize that the neural ensemble initially recruited by cocaine may be important for reinforcement learning, but that other ensembles of neurons in the nucleus accumbens may be recruited in order to mediate the transition to addiction.

Insights into nervous system repair from the fruit fly.

Millions of people experience injury to the central nervous system (CNS) each year, many of whom are left permanently disabled, providing a challenging hurdle for the field of regenerative medicine. Repair of damage in the CNS occurs through a concerted effort of phagocytosis of debris, cell proliferation and differentiation to produce new neurons and glia, distal axon/dendrite degeneration, proximal axon/dendrite regeneration and axon re-enwrapment. In humans, regeneration is observed within the peripheral nervous system, while in the CNS injured axons exhibit limited ability to regenerate. This has also been described for the fruit fly Drosophila. Powerful genetic tools available in Drosophila have allowed the response to CNS insults to be probed and novel regulators with mammalian orthologs identified. The conservation of many regenerative pathways, despite considerable evolutionary separation, stresses that these signals are principal regulators and may serve as potential therapeutic targets. Here, we highlight the role of Drosophila CNS injury models in providing key insight into regenerative processes by exploring the underlying pathways that control glial and neuronal activation in response to insult, and their contribution to damage repair in the CNS.

The Isolated Mouse Jejunal Afferent Nerve Assay as a Tool to Assess the Effect of Botulinum Neurotoxins in Visceral Nociception.

For the past two decades, botulinum neurotoxin A (BoNT/A) has been described as a strong candidate in the treatment of pain. With the production of modified toxins and the potential new applications at the visceral level, there is a real need for tools allowing the assessment of these compounds. In this study, we evaluated the jejunal mesenteric afferent nerve assay to investigate BoNT/A effects on visceral nociception. This ex vivo model allowed the continuous recording of neuronal activity in response to various stimuli. BoNT/A was applied intraluminally during three successive distensions, and the jejunum was distended every 15 min for 3 h. Finally, samples were exposed to external capsaicin. BoNT/A intoxication was validated at the molecular level with the presence of cleaved synaptosomal-associated protein of 25 (SNAP25) in nerve terminals in the mucosa and musculosa layers 3 h after treatment. BoNT/A had a progressive inhibitory effect on multiunit discharge frequency induced by jejunal distension, with a significant decrease from 1 h after application without change in jejunal compliance. The capsaicin-induced discharge was also affected by the toxin. This assay allowed the description of an inhibitory effect of BoNT/A on afferent nerve activity in response to distension and capsaicin, suggesting BoNT/A could alleviate visceral nociception.

Recurrent Excitatory Feedback From Mossy Cells Enhances Sparsity and Pattern Separation in the Dentate Gyrus via Indirect Feedback Inhibition.

It is generally appreciated that storing memories of specific events in the mammalian brain, and associating features of the environment with behavioral outcomes requires fine-tuning of the strengths of connections between neurons through synaptic plasticity. It is less understood whether the organization of neuronal circuits comprised of multiple distinct neuronal cell types provides an architectural prior that facilitates learning and memory by generating unique patterns of neuronal activity in response to different stimuli in the environment, even before plasticity and learning occur. Here we simulated a neuronal network responding to sensory stimuli, and systematically determined the effects of specific neuronal cell types and connections on three key metrics of neuronal sensory representations: sparsity, selectivity, and discriminability. We found that when the total amount of input varied considerably across stimuli, standard feedforward and feedback inhibitory circuit motifs failed to discriminate all stimuli without sacrificing sparsity or selectivity. Interestingly, networks that included dedicated excitatory feedback interneurons based on the mossy cells of the hippocampal dentate gyrus exhibited improved pattern separation, a result that depended on the indirect recruitment of feedback inhibition. These results elucidate the roles of cellular diversity and neural circuit architecture on generating neuronal representations with properties advantageous for memory storage and recall.

Early maternal separation alters the activation of stress-responsive brain areas in adulthood

The expression of c-Fos protein has been extensively used as a marker of neuronal activation in response to stressful stimuli. Early maternal separation (MS) is a model of early life adversity that affects the responsiveness of the brain areas to stressors. Thus, this study examined the impact of early MS on activating stress-responsive areas in the brain of adult rats in response to physical (ether) or psychological (restraint) stressors. Male pups were divided for the MS or non-handled (NH) groups. The MS was carried out daily between the 2nd and 14th day of postnatal life and consisted in removing the dams from the cage for 180 min. The rats were then subjected to experimental protocols of restraint or ether exposure at 10–12 weeks old. The rats were anesthetized 90 min after exposure to the stressors, and their brains were prepared for immunohistochemical analysis of c-Fos immunoreactive (c-Fos-ir) neurons in the hypothalamic paraventricular nucleus (PVN), supraoptic nucleus (SON), medial preoptic area (MPA), medial amygdaloid nucleus (MeA), locus coeruleus (LC), and nucleus of the solitary tract (NST). The MS-group presented 86%, 125%, 73%, 56%, and 137% higher c-Fos-ir neurons in the LC, PVN, SON, MPA, and MeA, respectively, compared to NH-group in response to the restraint stressor. In addition, the MS-group presented 180%, 137%, 170%, and 138% higher c-Fos-ir neurons for the ether exposure in the LC, PVN, MPA, and MeA, respectively. Our results show a greater increase in neuronal activation in the MS group, indicating that early life adversity can induce reprogramming in the brain response to stress in adulthood.

Influences of ethanol and temperature on sucrose-evoked response of gustatory neurons in the hamster solitary nucleus.

Taste-responsive neurons in the nucleus of the solitary tract (NST), the first gustatory nucleus, often respond to thermal or mechanical stimulation. Alcohol, not a typical taste modality, is a rewarding stimulus. In this study, we aimed to investigate the effects of ethanol (EtOH) and/or temperature as stimuli to the tongue on the activity of taste-responsive neurons in hamster NST. In the first set of experiments, we recorded the activity of 113 gustatory NST neurons in urethane-anesthetized hamsters and evaluated responses to four basic taste stimuli, 25% EtOH, and 40°C and 4°C distilled water (dH2O). Sixty cells responded to 25% EtOH, with most of them also being sucrose sensitive. The response to 25% EtOH was significantly correlated with the sucrose-evoked response. A significant correlation was also observed between sucrose- and 40°C dH2O- and between 25% EtOH- and 40°C dH2O-evoked firings. In a subset of the cells, we evaluated neuronal activities in response to a series of EtOH concentrations, alone and in combination with 32 mM sucrose (EtOH/Suc) at room temperature (RT, 22°C–23°C), 40°C, and 4°C. Neuronal responses to EtOH at RT and 40°C increased as the concentrations increased. The firing rates to EtOH/Suc were greater than those to EtOH or sucrose alone. The responses were enhanced when solutions were applied at 40°C but diminished at 4°C. In summary, EtOH activates most sucrose-responsive NST gustatory cells, and the concomitant presence of sucrose or warm temperatures enhance this response. Our findings may contribute to elucidate the neural mechanisms underlying appetitive alcohol consumption.

A randomized controlled trial of the GLP-1 receptor agonist dulaglutide in primary polydipsia.

BackgroundPrimary polydipsia, characterized by excessive fluid intake, carries the risk of water intoxication and hyponatremia, but treatment options are scarce. Glucagon-like peptide 1 (GLP-1) reduces appetite and food intake. In experimental models, GLP-1 has also been shown to play a role in thirst and drinking behavior. The aim of this trial was to investigate whether GLP-1 receptor agonists reduce fluid intake in patients with primary polydipsia.MethodsIn this randomized, double-blind, placebo-controlled, 3-week crossover trial, 34 patients with primary polydipsia received weekly dulaglutide (1.5 mg, Trulicity) in one treatment segment and placebo (0.9% sodium chloride) in the other. During the last treatment week, patients attended an 8-hour evaluation visit with free access to water. The primary endpoint was total fluid intake during the evaluation visits. Treatment effects were estimated using linear mixed-effects models. In a subset of 15 patients and an additional 15 matched controls, thirst perception and neuronal activity in response to beverage pictures were assessed by functional MRI.RESULTsPatients on dulaglutide reduced their fluid intake by 490 mL (95% CI: -780, -199; P = 0.002), from 2950 mL (95% CI: 2435, 3465) on placebo to 2460 mL (95% CI: 1946, 2475) on dulaglutide (model estimates), corresponding to a relative reduction of 17%. Twenty-four-hour urinary output was reduced by -943 mL (95% CI: -1473, -413; P = 0.001). Thirst perception in response to beverage pictures was higher for patients with primary polydipsia than for controls, and lower for patients on dulaglutide versus placebo, but functional activity was similar among groups and treatments.CONCLUSIONSGLP-1 receptor agonists reduce fluid intake and thirst perception in patients with primary polydipsia and could therefore be a treatment option for these patients.Trial registrationClinicaltrials.gov NCT02770885.FundingSwiss National Science Foundation (grant 32473B_162608); University Hospital and University of Basel; Young Talents in Clinical Research grant from the Swiss Academy of Medical Sciences and the Gottfried & Julia Bangerter-Rhyner Foundation; Top-up Grant from the PhD Programme in Health Sciences, University of Basel.

Distinct contribution of cone photoreceptor subtypes to the mammalian biological clock

Ambient light detection is important for the synchronization of the circadian clock to the external solar cycle. Light signals are sent to the suprachiasmatic nuclei (SCN), the site of the major circadian pacemaker. It has been assumed that cone photoreceptors contribute minimally to synchronization. Here, however, we find that cone photoreceptors are sufficient for mediating entrainment and transmitting photic information to the SCN, as evaluated in mice that have only cones as functional photoreceptors. Using in vivo electrophysiological recordings in the SCN of freely moving cone-only mice, we observed light responses in SCN neuronal activity in response to 60-s pulses of both ultraviolet (UV) (λmax 365 nm) and green (λmax 505 nm) light. Higher irradiances of UV light led to irradiance-dependent enhancements in SCN neuronal activity, whereas higher irradiances of green light led to a reduction in the sustained response with only the transient response remaining. Responses in SCN neuronal activity decayed with a half-max time of ∼9 min for UV light and less than a minute for green light, indicating differential input between short-wavelength-sensitive and mid-wavelength-sensitive cones for the SCN responsiveness. Furthermore, we show that UV light is more effective for photoentrainment than green light. Based on the lack of a full sustained response in cone-only mice, we confirmed that rapidly alternating light levels, rather than slowly alternating light, caused substantial phase shifts. Together, our data provide strong evidence that cone types contribute to photoentrainment and differentially affect the electrical activity levels of the SCN.

Whole-brain mapping of amylin-induced neuronal activity in receptor activity-modifying protein 1/3 knockout mice.

The pancreatic hormone amylin plays a central role in regulating energy homeostasis and glycaemic control by stimulating satiation and reducing food reward, making amylin receptor agonists attractive for the treatment of metabolic diseases. Amylin receptors consist of heterodimerized complexes of the calcitonin receptor and receptor-activity modifying proteins subtype 1-3 (RAMP1-3). Neuronal activation in response to amylin dosing has been well characterized, but only in selected regions expressing high levels of RAMPs. The current study identifies global brain-wide changes in response to amylin and by comparing wild type and RAMP1/3 knockout mice reveals the importance of RAMP1/3 in mediating this response. Amylin dosing resulted in neuronal activation as measured by an increase in c-Fos labelled cells in 20 brain regions, altogether making up the circuitry of neuronal appetite regulation (e.g., area postrema (AP), nucleus of the solitary tract (NTS), parabrachial nucleus (PB), and central amygdala (CEA)). c-Fos response was also detected in distinct nuclei across the brain that typically have not been linked with amylin signalling. In RAMP1/3 knockout amylin induced low-level neuronal activation in seven regions, including the AP, NTS and PB, indicating the existence of RAMP1/3-independent mechanisms of amylin response. Under basal conditions RAMP1/3 knockout mice show reduced neuronal activity in the hippocampal formation as well as reduced hippocampal volume, suggesting a role for RAMP1/3 in hippocampal physiology and maintenance. Altogether these data provide a global map of amylin response in the mouse brain and establishes the significance of RAMP1/3 receptors in relaying this response.

GLP1 Receptor Agonists Reduce Fluid Intake in Primary Polydipsia

Background Primary polydipsia, characterized by excessive fluid intake, carries the risk of water intoxication and hyponatremia, but treatment options are scarce. Glucagon-like peptide-1 (GLP-1) reduces appetite and food intake. In experimental models, they also play a role in thirst and drinking behavior in. The aim of this trial was to investigate whether GLP-1 receptor agonists reduce fluid intake in patients with primary polydipsia. Methods: In this randomized, double-blind, placebo-controlled, 3-week crossover-trial, 34 patients with primary polydipsia received weekly dulaglutide (Trulicity®) 1.5mg and placebo (0.9% sodium chloride). During the last treatment week, patients attended an 8-hour evaluation visit with free water access. The primary endpoint was total fluid intake during the evaluation visits. The treatment effect was estimated using a linear mixed-effects model. In a subset of 15 patients and matched controls, thirst perception and neuronal activity in response to beverage pictures were assessed by functional MRI. Results Median [IQR] total fluid intake was 2250ml [1600-2600] on dulaglutide versus 2400ml [1850-3400] on placebo. Patients on dulaglutide reduced fluid intake by 490ml [95%-CI -780, -199], p=0.002, corresponding to a relative reduction of 17%. 24-hour urinary output was reduced by -943ml [95%-CI -1473, -413]. Thirst perception in response to beverage pictures was higher in patients with primary polydipsia versus controls and lower on dulaglutide versus placebo, but functional neuronal activity was similar between groups and treatments. Conclusion: GLP-1 receptor agonists reduce fluid intake and thirst perception in patients with primary polydipsia and could therefore be a novel treatment option for these patients.

Neural adaptation

The term 'neural adaptation' refers to the common phenomenon of decaying neuronal activities in response to repeated or prolonged stimulation. Many different roles of adaptation in neural computations have been discussed. On a single-cell level adaptation introduces a high-pass filter operation as a basic element for predictive coding. Interactions of adaptation processes with nonlinearities are key to many more computations including generation of invariances, stimulus selectivity, denoising, and sparsening. Neural adaptation is observed all the way along neuronal pathways from the sensory periphery to the motor output and adaptation usually gets stronger at higher levels. Non-adapting neurons or neurons that increase their sensitivity are rare exceptions. What computations arise by repeated adaptation mechanisms along a processing pathway? After giving some background on neural adaptation, underlying mechanisms, dynamics, and resulting filter properties, I will discuss computational properties of four examples of serial and parallel adaptation processes, demonstrating that adaptation acts together with other mechanisms, in particular threshold nonlinearities, to eventually compute meaningful perceptions. Python code and further details of the simulations illustrating this primer are available at https://github.com/janscience/adaptationprimer.

Early life maternal deprivation attenuates morphine induced inhibition in lateral paragigantocellularis neurons in adult rats

Early life stress can serve as one of the principle sources leading to individual differences in confronting challenges throughout the lifetime. Maternal deprivation (MD), a model of early life stress, can cause persistent alterations in brain function, and it may constitute a risk factor for later incidence of drug addiction. It is becoming more apparent that early life MD predisposes opiate abuse in adulthood. Although several behavioral and molecular studies have addressed this issue, changes in electrophysiological features of the neurons are yet to be understood. The lateral paragigantocellularis (LPGi) nucleus, which participates in the mediation of opiate dependence and withdrawal, may be susceptible to modifications following MD. This study sought to find whether early life MD can alter the discharge activity of LPGi neurons and their response to acute morphine administration in adult rats.Male Wistar rats experienced MD on postnatal days (PNDs) 1–14 for three h per day. Afterward, they were left undisturbed until PND 70, during which the extracellular activities of LPGi neurons were recorded in anesthetized animals at baseline and in response to acute morphine.In both MD and control groups, acute morphine administration induced heterogeneous (excitatory, inhibitory, and no effect) responses in LPGi neurons. At baseline recording, the interspike interval variability of the LPGi neurons was attenuated in both inhibitory and excitatory responses in animals with the history of MD. The extent of morphine-induced discharge inhibition was also lower in deprived animals compared to the control group.These findings suggest that early life MD induces long-term alterations in LPGi neuronal activity in response to acute administration of morphine. Therefore, the MD may alter the vulnerability to develop opiate abuse in adulthood.

Neuronal Responses to Short Wavelength Light Deficiency in the Rat Subcortical Visual System.

The amount and spectral composition of light changes considerably during the day, with dawn and dusk being the most crucial moments when light is within the mesopic range and short wavelength enriched. It was recently shown that animals use both cues to adjust their internal circadian clock, thereby their behavior and physiology, with the solar cycle. The role of blue light in circadian processes and neuronal responses is well established, however, an unanswered question remains: how do changes in the spectral composition of light (short wavelengths blocking) influence neuronal activity? In this study we addressed this question by performing electrophysiological recordings in image (dorsal lateral geniculate nucleus; dLGN) and non-image (the olivary pretectal nucleus; OPN, the suprachiasmatic nucleus; SCN) visual structures to determine neuronal responses to spectrally varied light stimuli. We found that removing short-wavelength from the polychromatic light (cut off at 525 nm) attenuates the most transient ON and sustained cells in the dLGN and OPN, respectively. Moreover, we compared the ability of different types of sustained OPN neurons (either changing or not their response profile to filtered polychromatic light) to irradiance coding, and show that both groups achieve it with equal efficacy. On the other hand, even very dim monochromatic UV light (360 nm; log 9.95 photons/cm2/s) evokes neuronal responses in the dLGN and SCN. To our knowledge, this is the first electrophysiological experiment supporting previous behavioral findings showing visual and circadian functions disruptions under short wavelength blocking environment. The current results confirm that neuronal activity in response to polychromatic light in retinorecipient structures is affected by removing short wavelengths, however, with type and structure – specific action. Moreover, they show that rats are sensitive to even very dim UV light.

Cognitive deficits correlated with increased latency of event-related potentials in drug-free patients with generalized anxiety disorder

Objective: Few studies have identified a relationship between cognitive deficits and altered event-related potentials (ERPs), which measure the synchronous activity of neurons in response to a stimulus in patients with generalized anxiety disorder (GAD). In this study, we intended to explore the relation between cognitive function and ERP in patients with GAD. Methods: Fourteen drug-free participants with GAD and 14 healthy controls were recruited. ERPs were measured, and neuropsychological tests were administered. We compared the differences of the data between two groups of the study participants. Results: Poor performances of full IQ and the numbers of the categories completed on the Wisconsin Card Sorting Test were found significantly correlated with increased frontal lobe latency in the patients with GAD (Spearman's ρ = −0.70, p

Infrared nanospectroscopy study of the light-induced conformational changes of Channelrhodopsin

The channelrhodopsin-ChR2 is a light-sensitive transmembrane protein that acts as a selective ion channel between the intra- and the extra-cellular environments. In the last decade, ChR2 has proven to be essential for optogenetics, because, if expressed in mammalian neural cells, it enables the control of neuronal activity in response to visible light. Mid-infrared difference spectroscopy can probe the functional conformational changes of light-sensitive proteins, however intrinsic limitations of standard IR spectroscopy in terms of diffraction, and therefore number of probed proteins, require that the mid-IR experiments be performed on huge numbers of lipid membrane patches with overexpressed proteins. In this work, we apply for the first time IR difference nanospectroscopy, based on the use of mid-IR lasers and an atomic force microscope (AFM), to single membrane patches containing ChR2, obtaining relevant spectroscopy results for optogenetic applications and, more generally, for future experimental studies of light-sensitive proteins at the nanoscale.

Neural responses to food cues in middle to older aged adults: a scoping review of fMRI studies.

Understanding neural responses through functional magnetic resonance imaging (fMRI) to food and food cues in middle-older adults may lead to better treatment options to address the growing issue of malnutrition. This scoping review aimed to determine the extent, range and nature of research using fMRI, related to reward-based regions, in response to food cues in middle to older aged adults (50 years and over). The following databases were systematically searched in July 2019: CINAHL, CENTRAL, Embase, Dissertations and Theses, Ovid Medline, PsycINFO, PsycEXTRA, Scopus and Web of Science. Studies were eligible for inclusion if participants had a mean or median age ≥50 years, utilised and reported outcomes of either a food cue task-related fMRI methodology or resting-state fMRI. Data from included studies were charted, and synthesised narratively. Twenty-two studies were included. Eighteen studies utilised a task-related design to measure neural activation, two studies measured resting state neural connectivity only and an additional two studies measured both. The fMRI scanning paradigms, food cue tools and procedure of presentation varied markedly. Four studies compared the neural responses to food between younger and older adults, providing no consensus on neural age-related changes to food cues; two studies utilised longitudinal scans. This review identified significant extent, range and nature in the approaches used to assess neuronal activity in response to food cues in adults aged 50 years and over. Future studies are needed to understand the age-related appetite changes whilst considering personal preferences for food cues.

The Paraventricular Nucleus of the Thalamus Is an Important Node in the Emotional Processing Network.

The paraventricular nucleus of the thalamus (PVT) has for decades been acknowledged to be an important node in the limbic system, but studies of emotional processing generally fail to incorporate it into their investigational framework. Here, we propose that the PVT should be considered as an integral part of the emotional processing network. Through its distinct subregions, cell populations, and connections with other limbic nuclei, the PVT participates in both major features of emotion: arousal and valence. The PVT, particularly the anterior PVT, can through its neuronal activity promote arousal, both as part of the sleep-wake cycle and in response to novel stimuli. It is also involved in reward, being both responsive to rewarding stimuli and itself affecting behavior reflecting reward, likely via specific populations of cells distributed throughout its subregions. Similarly, neuronal activity in the PVT contributes to depression-like behavior, through yet undefined subregions. The posterior PVT in particular demonstrates a role in anxiety-like behavior, generally promoting but also inhibiting this behavior. This subregion is also especially responsive to stressors, and it functions to suppress the stress response following chronic stress exposure. In addition to participating in unconditioned or primary emotional responses, the PVT also makes major contributions to conditioned emotional behavior. Neuronal activity in response to a reward-predictive cue can be detected throughout the PVT, and endogenous activity in the posterior PVT strongly predicts approach or seeking behavior. Similarly, neuronal activity during conditioned fear retrieval is detected in the posterior PVT and its activation facilitates the expression of conditioned fear. Much of this involvement of the PVT in arousal and valence has been shown to occur through the same general afferents and efferents, including connections with the hypothalamus, prelimbic and infralimbic cortices, nucleus accumbens, and amygdala, although a detailed functional map of the PVT circuits that control emotional responses remains to be delineated. Thus, while caveats exist and more work is required, the PVT, through its extensive connections with other prominent nuclei in the limbic system, appears to be an integral part of the emotional processing network.