The Experts below are selected from a list of 222 Experts worldwide ranked by ideXlab platform
Robert A Dekemp - One of the best experts on this subject based on the ideXlab platform.
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first in human imaging and kinetic analysis of vesicular acetylcholine transporter density in the heart using 18 f feobv pet
Journal of Nuclear Cardiology, 2020Co-Authors: Zacharie Saintgeorges, Vanessa Zayed, Katie Dinelle, Clifford Cassidy, Jeanpaul Soucy, Gassan Massarweh, Benjamin H Rotstein, Pablo B Nery, Synthia Guimond, Robert A DekempAbstract:In contrast to cardiac sympathetic Activity which can be assessed with established PET tracers, there are currently no suitable radioligands to measure cardiac parasympathetic (Cholinergic) Activity. A radioligand able to measure cardiac Cholinergic Activity would be an invaluable clinical and research tool since Cholinergic dysfunction has been associated with a wide array of pathologies (e.g., chronic heart failure, myocardial infarction, arrythmias). [18F]Fluoroethoxybenzovesamicol (FEOBV) is a Cholinergic radiotracer that has been extensively validated in the brain. Whether FEOBV PET can be used to assess Cholinergic Activity in the heart is not known. Hence, this study aimed to evaluate the properties of FEOBV for cardiac PET imaging and Cholinergic Activity mapping. PET data were collected for 40 minutes after injection of 230 ± 50 MBq of FEOBV in four healthy participants (1 female; Age: 37 ± 10; BMI: 25 ± 2). Dynamic LV time Activity curves were fitted with Logan graphical, 1-tissue compartment, and 2-tissue compartment models, yielding similar distribution volume estimates for each participant. Our initial data show that FEOBV PET has favorable tracer kinetics for quantification of Cholinergic Activity and is a promising new method for assessing parasympathetic function in the heart.
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First-in-human imaging and kinetic analysis of vesicular acetylcholine transporter density in the heart using [^18F]FEOBV PET
Journal of Nuclear Cardiology, 2020Co-Authors: Zacharie Saint-georges, Katie Dinelle, Clifford Cassidy, Jeanpaul Soucy, Gassan Massarweh, Pablo B Nery, Synthia Guimond, Vanessa K. Zayed, Benjamin Rotstein, Robert A DekempAbstract:In contrast to cardiac sympathetic Activity which can be assessed with established PET tracers, there are currently no suitable radioligands to measure cardiac parasympathetic (Cholinergic) Activity. A radioligand able to measure cardiac Cholinergic Activity would be an invaluable clinical and research tool since Cholinergic dysfunction has been associated with a wide array of pathologies (e.g., chronic heart failure, myocardial infarction, arrythmias). [^18F]Fluoroethoxybenzovesamicol (FEOBV) is a Cholinergic radiotracer that has been extensively validated in the brain. Whether FEOBV PET can be used to assess Cholinergic Activity in the heart is not known. Hence, this study aimed to evaluate the properties of FEOBV for cardiac PET imaging and Cholinergic Activity mapping. PET data were collected for 40 minutes after injection of 230 ± 50 MBq of FEOBV in four healthy participants (1 female; Age: 37 ± 10; BMI: 25 ± 2). Dynamic LV time Activity curves were fitted with Logan graphical, 1-tissue compartment, and 2-tissue compartment models, yielding similar distribution volume estimates for each participant. Our initial data show that FEOBV PET has favorable tracer kinetics for quantification of Cholinergic Activity and is a promising new method for assessing parasympathetic function in the heart.
Thomas P. Durkin - One of the best experts on this subject based on the ideXlab platform.
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GABAergic mediation of indirect transsynaptic control over basal and spatial memory testing-induced activation of septo-hippocampal Cholinergic Activity in mice *
Behavioural Brain Research, 1992Co-Authors: Thomas P. DurkinAbstract:A neurochemical study of the transsynaptic interactions established between septal GABAergic interneurones and Cholinergic septo-hippocampal neurones was conducted using mice. The effects of acute in vivo injections of either muscimol (20–500 ng/0.2 μl), bicuculline (100 ng–1 μg/0.2μl) or saline vehicle (0.2 μl) into the medial septum on septo-hippocampal Cholinergic Activity were evaluated using measures of hippocampal high affinity choline uptake at 30 min post-injection in two main groups of mice. The first (quiet control) remained in their home cages during the post-injection period whereas the second (active) were submitted, 10 min following injection to a 20-min period of spatial working memory testing in an 8-arm radial maze. Intraseptal injections of either muscimol or bicuculline produced significant (25–50%) inhibition of hippocampal Cholinergic Activity in quiet conditions (basal) as compared to intact or saline-injected mice. In the active groups, whereas memory testing induced significant Cholinergic activation (+15–20%) in intact and saline injected mice at 30 s post-test no significant memory testing-induced activation was observed in either muscimol or bicuculline-injected mice at any dose. The role of septal GABAergic interneurones in the indirect transsynaptic control over the basal and activated states of septo-hippocampal Cholinergic Activity is discussed with respect to the concept that these complex neuronal interactions contribute to the physiological mechanisms involved in the modulation of working memory performance.
T P Durkin - One of the best experts on this subject based on the ideXlab platform.
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GABAergic mediation of indirect transsynaptic control over basal and spatial memory testing-induced activation of septo-hippocampal Cholinergic Activity in mice.
Behavioural brain research, 1992Co-Authors: T P DurkinAbstract:A neurochemical study of the transsynaptic interactions established between septal GABAergic interneurones and Cholinergic septo-hippocampal neurones was conducted using mice. The effects of acute in vivo injections of either muscimol (20-500 ng/0.2 microliter), bicuculline (100 ng-1 micrograms/0.2 microliter) or saline vehicle (0.2 microliter) into the medial septum on septo-hippocampal Cholinergic Activity were evaluated using measures of hippocampal high affinity choline uptake at 30 min post-injection in two main groups of mice. The first (quiet control) remained in their home cages during the post-injection period whereas the second (active) were submitted, 10 min following injection to a 20-min period of spatial working memory testing in an 8-arm radial maze. Intraseptal injections of either muscimol or bicuculline produced significant (25-50%) inhibition of hippocampal Cholinergic Activity in quiet conditions (basal) as compared to intact or saline-injected mice. In the active groups, whereas memory testing induced significant Cholinergic activation (+15-20%) in intact and saline injected mice at 30 s post-test no significant memory testing-induced activation was observed in either muscimol or bicuculline-injected mice at any dose. The role of septal GABAergic interneurones in the indirect transsynaptic control over the basal and activated states of septo-hippocampal Cholinergic Activity is discussed with respect to the concept that these complex neuronal interactions contribute to the physiological mechanisms involved in the modulation of working memory performance.
Martin Sarter - One of the best experts on this subject based on the ideXlab platform.
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diverse roads to relapse a discriminative cue signaling cocaine availability is more effective in renewing cocaine seeking in goal trackers than sign trackers and depends on basal forebrain Cholinergic Activity
The Journal of Neuroscience, 2017Co-Authors: Kyle K Pitchers, Kyra B Phillips, Jonte L Jones, Terry E Robinson, Martin SarterAbstract:Stimuli associated with taking drugs are notorious instigators of relapse. There is, however, considerable variation in the motivational properties of such stimuli, both as a function of the individual and the nature of the stimulus. The behavior of some individuals (sign trackers, STs) is especially influenced by cues paired with reward delivery, perhaps because they are prone to process information via dopamine-dependent, cue-driven, incentive salience systems. Other individuals (goal trackers, GTs) are better able to incorporate higher-order contextual information, perhaps because of better executive/attentional control over behavior, which requires frontal cortical Cholinergic Activity. We hypothesized, therefore, that a cue that "sets the occasion" for drug taking (a discriminative stimulus, DS) would reinstate cocaine seeking more readily in GTs than STs and that this would require intact Cholinergic neurotransmission. To test this, male STs and GTs were trained to self-administer cocaine using an intermittent access schedule with periods of cocaine availability and unavailability signaled by a DS+ and a DS-, respectively. Thereafter, half of the rats received an immunotoxic lesion that destroyed 40-50% of basal forebrain Cholinergic neurons and later, after extinction training, were tested for the ability of noncontingent presentations of the DS+ to reinstate cocaine seeking behavior. The DS+ was much more effective in reinstating cocaine seeking in GTs than STs and this effect was abolished by Cholinergic losses despite the fact that all rats continued to orient to the DS+ We conclude that vulnerability to relapse involves interactions between individual cognitive-motivational biases and the form of the drug cue encountered.SIGNIFICANCE STATEMENT The most predictable outcome of a diagnosis of addiction is a high chance for relapse. When addicts encounter cues previously associated with drug, their attention may be unduly attracted to such cues and these cues can evoke motivational states that instigate and maintain drug-seeking behavior. Although sign-tracking rats were previously demonstrated to exhibit greater relapse vulnerability to Pavlovian drug cues paired with drug delivery, here, we demonstrate that their counterparts, the goal trackers, are more vulnerable if the drug cue acts to signal drug availability and that the forebrain Cholinergic system mediates such vulnerability. Given the importance of contextual cues for triggering relapse and the human cognitive-Cholinergic capacity for the processing of such cues, goal trackers model essential aspects of relapse vulnerability.
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Cholinergic mediation of attention: contributions of phasic and tonic increases in prefrontal Cholinergic Activity.
Annals of the New York Academy of Sciences, 2008Co-Authors: Vinay Parikh, Martin SarterAbstract:Contrary to the classic description of acetylcholine (ACh) as a slowly acting neuromodulator that influences arousal states, results from experiments that employed enzyme-selective microelectrodes for the real-time monitoring of ACh release in the cortex of attentional task-performing rats indicate that Cholinergic signals manifesting on multiple timescales (seconds, tens of seconds, and minutes) support, and are necessary for, the mediation of defined cognitive operations. Specifically, in the prefrontal cortex, second-based Cholinergic signals support the detection of behaviorally significant cues. In contrast to these prefrontal Cholinergic transients, performance-associated Cholinergic Activity that manifested at lower temporal resolution also was observed elsewhere in the cortex. Although tonic Cholinergic signal levels were correlated with the amplitudes of cue-evoked Cholinergic transients, and the latter with response latencies, the interrelationships and interactions between the multiple Cholinergic signaling modes remains unclear. Hypotheses concerning the afferent circuitry contributing to the regulation of second- versus minute-based Cholinergic signals are discussed. The discovery of Cholinergic transients and their crucial role in cue detection and attentional performance form the basis for new hypotheses about the nature of Cholinergic dysfunction in cognitive disorders and offer new targets for the development of treatments for the cognitive symptoms of neuropsychiatric and neurodegenerative disorders.
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prefrontal acetylcholine release controls cue detection on multiple timescales
Neuron, 2007Co-Authors: Vinay Parikh, Rouba Kozak, Vicente Martinez, Martin SarterAbstract:Cholinergic neurons originating from the basal forebrain innervate the entire cortical mantle. Choline-sensitive microelectrodes were used to measure the synaptic release of cortical acetylcholine (ACh) at a subsecond resolution in rats performing a task involving the detection of cues. Cues that were detected, defined behaviorally, evoked transient increases in Cholinergic Activity (at the scale of seconds) in the medial prefrontal cortex (mPFC), but not in a nonassociational control region (motor cortex). In trials involving missed cues, Cholinergic transients were not observed. Cholinergic deafferentation of the mPFC, but not motor cortex, impaired cue detection. Furthermore, decreases and increases in precue Cholinergic Activity predicted subsequent cue detection or misses, respectively. Finally, cue-evoked Cholinergic transients were superimposed over slower (at the timescale of minutes) changes in Cholinergic Activity. Cortical Cholinergic neurotransmission is regulated on multiple timescales to mediate the detection of behaviorally significant cues and to support cognitive performance.
María Isabel Miranda - One of the best experts on this subject based on the ideXlab platform.
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blockade of nucleus basalis magnocellularis or activation of insular cortex histamine receptors disrupts formation but not retrieval of aversive taste memory
Neurobiology of Learning and Memory, 2010Co-Authors: Liliana Puronsierra, Elizabeth Sabath, Luis Nunezjaramillo, María Isabel MirandaAbstract:Abstract Recent research, using several experimental models, demonstrated that the histaminergic system is clearly involved in memory formation. This evidence suggested that during different associative learning tasks, histamine receptor subtypes have opposite functions, related to the regulation of cortical Cholinergic Activity. Given that cortical Cholinergic Activity and nucleus basalis magnocellularis (NBM) integrity are needed during taste memory formation, the aim of this study was to determine the role of histamine receptors during conditioned taste aversion (CTA). We evaluated the effects of bilateral infusions of 0.5 μl of pyrilamine (100 mM), an H1 receptor antagonist, into the NBM, or of R-α-methylhistamine (RAMH) (10 mM), an H3 receptor agonist, into the insular cortex of male Sprague-Dawley rats 20 min before acquisition and/or retrieval of conditioned taste aversion. The results showed that blockade of H1 receptors in NBM or activation of H3 receptors in the insular cortex impairs formation but not retrieval of aversive taste memory. These results demonstrated differential roles for histamine receptors in two important areas for taste memory formation and suggest that these effects could be related with the cortical Cholinergic Activity modulation during CTA acquisition.
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Cholinergic Activity in the insular cortex is necessary for acquisition and consolidation of contextual memory
Neurobiology of learning and memory, 2006Co-Authors: María Isabel Miranda, Federico Bermúdez-rattoniAbstract:Experiences with a high emotional content (aversive) tend to be stored as long-term memories; however, there are also contextual recollections, which form a significant part of our memories. Different research has shown that the insular cortex (IC) plays an important role during aversive memory formation, yet its role during incidental/non-aversive learning like pre-exposure contextual memory formation has received little attention. The objective of this research was to establish the role of Cholinergic Activity in the IC through its muscarinic receptors during the formation of inhibitory avoidance (IA) memory, as well as during pre-exposure contextual memory, using a paradigm such as latent inhibition (LI). Rats with bilateral cannulae directed into the IC were trained in the LI paradigm of IA or IA task alone. The muscarinic antagonist receptor scopolamine was infused bilaterally into the IC 5 min before the pre-exposure into the dark chamber of the IA cage, one day before the conventional IA training or during the IA training day. During the IA test, the entrance latency into the dark chamber of the IA cage was measured as an index of contextual memory. The results showed that scopolamine infused before and after IA training disrupts inhibitory avoidance memory. Also, it showed that the pre-exposed saline-infused animals (LI) had a lower entrance latency compared to the group not pre-exposed (IA). However, the group that received scopolamine into the IC before, but not after, the pre-exposure to the dark chamber, presented a similar latency to the IA group, showing a blockade of the latent inhibition of the IA. These results suggest that Cholinergic Activity in the insular cortex is necessary during the acquisition and consolidation of avoidance memory, but appears necessary only during the acquisition of pre-exposure non-aversive contextual memory.
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cortical Cholinergic Activity is related to the novelty of the stimulus
Brain Research, 2000Co-Authors: María Isabel Miranda, Leticia Ramirezlugo, Federico BermudezrattoniAbstract:A number of studies have related Cholinergic Activity to the mediation of learning and memory. However, the acetylcholine (ACh) participation has been recently implicated in the early stages of memory formation but not during retrieval. The aim of the present study is to evaluate ACh release in the insular cortex (IC) during presentation of different taste stimuli and during their re-exposition by means of the free-moving microdialysis technique. We evaluated the changes in ACh release when a novel taste, saccharin or quinine was presented to the rat and after several presentations of saccharin. Unilateral microdialysis was performed in the IC 1 h before and 1 h after the presentation of: (1) a familiar stimulus (water), (2) a novel taste (quinine), (3) another novel taste (saccharin), (4) a second presentation, (5) a third presentation, and (6) a fourth presentation of saccharin. The volume consumed by the animals was registered as a behavioral parameter. The ACh levels from the microdialysis fractions were analyzed by an HPLC-ED system. Biochemical results showed a significant increment in the cortical ACh release induced by a novel stimulus compared with the release observed during the presentation of a familiar stimulus. The ACh release observed after several presentations of the stimuli decreased to the same levels as those produced by the familiar taste, indicating an inverse relationship between familiarity and cortical ACh release. These results suggest that the Cholinergic system plays an important role in the identification and characterization of different kinds of stimuli.