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https://www.readbyqxmd.com/read/29786639/chemogenetic-enhancement-of-axon-regeneration-following-peripheral-nerve-injury-in-the-slick-a-mouse
#1
Poonam B Jaiswal, Olivia C Mistretta, Patricia J Ward, Arthur W English
The effects of chemogenetics on axon regeneration following peripheral nerve transection and repair were studied in mice expressing a Cre-dependent excitatory designer receptor exclusively activated by designer drugs (DREADD) and Cre-recombinase/yellow fluorescent protein (YFP) in a subset of motor and sensory neurons and cortical motoneurons (SLICK-A). Sciatic nerves were cut and repaired and mice were treated either once, at the time of injury, or five days per week for two weeks with clozapine N-oxide (CNO) (1 mg/kg, i...
May 22, 2018: Brain Sciences
https://www.readbyqxmd.com/read/29754898/replay-of-episodic-memories-in-the-rat
#2
Danielle Panoz-Brown, Vishakh Iyer, Lawrence M Carey, Christina M Sluka, Gabriela Rajic, Jesse Kestenman, Meredith Gentry, Sydney Brotheridge, Isaac Somekh, Hannah E Corbin, Kjersten G Tucker, Bianca Almeida, Severine B Hex, Krysten D Garcia, Andrea G Hohmann, Jonathon D Crystal
Vivid episodic memories in people have been characterized as the replay of multiple unique events in sequential order [1-3]. The hippocampus plays a critical role in episodic memories in both people and rodents [2, 4-6]. Although rats remember multiple unique episodes [7, 8], it is currently unknown if animals "replay" episodic memories. Therefore, we developed an animal model of episodic memory replay. Here, we show that rats can remember a trial-unique stream of multiple episodes and the order in which these events occurred by engaging hippocampal-dependent episodic memory replay...
April 21, 2018: Current Biology: CB
https://www.readbyqxmd.com/read/29705849/application-of-chemogenetics-and-optogenetics-to-dissect-brain-immune-interactions
#3
Ben Korin, Asya Rolls
For many years, the complexity and multifactorial nature of brain-immune interactions limited our ability to dissect their underlying mechanisms. An especially challenging question was how the brain controls immunity, since the repertoire of techniques to control the brain's activity was extremely limited. New tools, such as optogenetics and chemogenetics (e.g., DREADDs), developed over the last decade, opened new frontiers in neuroscience with major implications for neuroimmunology. These tools enable mapping the causal effects of activating/attenuating defined neurons in the brain, on the immune system...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29660441/silencing-the-insular-striatal-circuit-decreases-alcohol-self-administration-and-increases-sensitivity-to-alcohol
#4
Anel A Jaramillo, Kalynn Van Voorhies, Patrick A Randall, Joyce Besheer
Internal drug states/cues can impact drug taking, as pretreatment with a moderate to high alcohol dose (i.e., loading dose) can decrease subsequent alcohol self-administration, alcohol-seeking, and relapse-like drinking. The insular cortex (IC) is implicated in processing information about internal states and findings show that silencing the IC and its projections to the nucleus accumbens core (AcbC) enhance sensitivity to the interoceptive effects of alcohol. Therefore, the goal of the present work was to determine the functional role of IC-AcbC projections in modulating the effects of alcohol pretreatment on operant alcohol self-administration...
April 13, 2018: Behavioural Brain Research
https://www.readbyqxmd.com/read/29507292/fear-extinction-requires-infralimbic-cortex-projections-to-the-basolateral-amygdala
#5
Daniel W Bloodgood, Jonathan A Sugam, Andrew Holmes, Thomas L Kash
Fear extinction involves the formation of a new memory trace that attenuates fear responses to a conditioned aversive memory, and extinction impairments are implicated in trauma- and stress-related disorders. Previous studies in rodents have found that the infralimbic prefrontal cortex (IL) and its glutamatergic projections to the basolateral amygdala (BLA) and basomedial amygdala (BMA) instruct the formation of fear extinction memories. However, it is unclear whether these pathways are exclusively involved in extinction, or whether other major targets of the IL, such as the nucleus accumbens (NAc) also play a role...
March 6, 2018: Translational Psychiatry
https://www.readbyqxmd.com/read/29507147/activity-dependent-myelination-of-parvalbumin-interneurons-mediated-by-axonal-morphological-plasticity
#6
Jeffrey Stedehouder, Demi Brizee, Guy Shpak, Steven A Kushner
Axonal myelination of neocortical pyramidal neurons is modulated dynamically by neuronal activity. Recent studies have shown that a substantial proportion of neocortical myelin content is contributed by fast-spiking, parvalbumin (PV)-positive interneurons. However, it remains unknown whether the myelination of PV+ interneurons is also modulated by intrinsic activity. Here, we used cell-type-specific Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) in adult mice to activate a sparse population of medial prefrontal cortex (mPFC) PV+ interneurons...
April 11, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29500819/cyclic-amp-producing-chemogenetic-activation-of-indirect-pathway-striatal-projection-neurons-and-the-downstream-effects-on-the-globus-pallidus-and-subthalamic-nucleus-in-freely-moving-mice
#7
Safa Bouabid, Fu-Ming Zhou
The indirect pathway striatal medium spiny projection neurons (iMSNs) are critical to motor and cognitive brain functions. These neurons express a high level of cAMP-increasing adenosine A2a receptors. However, the potential effects of cAMP production on iMSN spiking activity have not been established, and recording identified iMSNs in freely moving animals is challenging. Here, we show that in the transgenic mice expressing cAMP-producing G protein Gs -coupled designer receptor exclusively activated by designer drug (Gs-DREADD) in iMSNs, the baseline spike firing in MSNs is normal, indicating DREADD expression does not affect the normal physiology of these neurons...
March 3, 2018: Journal of Neurochemistry
https://www.readbyqxmd.com/read/29453443/role-of-the-mesolimbic-dopamine-system-in-relief-learning
#8
Dana Mayer, Evelyn Kahl, Taygun C Uzuneser, Markus Fendt
The relief from an aversive event is rewarding. Since organisms are able to learn which environmental cues can cease an aversive event, relief learning helps to better cope with future aversive events. Literature data suggest that relief learning is affected in various psychopathological conditions, such as anxiety disorders. Here, we investigated the role of the mesolimbic dopamine system in relief learning. Using a relief learning procedure in Sprague Dawley rats, we applied a combination of behavioral experiments with anatomical tracing, c-Fos immunohistochemistry, and local chemogenetic and pharmacological interventions to broadly characterize the role of the mesolimbic dopamine system...
February 5, 2018: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/29453206/elevation-of-hippocampal-neurogenesis-induces-a-temporally-graded-pattern-of-forgetting-of-contextual-fear-memories
#9
Aijing Gao, Frances Xia, Axel J Guskjolen, Adam I Ramsaran, Adam Santoro, Sheena A Josselyn, Paul W Frankland
Throughout life neurons are continuously generated in the subgranular zone of the hippocampus. The subsequent integration of newly generated neurons alters patterns of dentate gyrus input and output connectivity, potentially rendering memories already stored in those circuits harder to access. Consistent with this prediction, we previously showed that increasing hippocampal neurogenesis after training induces forgetting of hippocampus-dependent memories, including contextual fear memory. However, the brain regions supporting contextual fear memories change with time, and this time-dependent memory reorganization might regulate the sensitivity of contextual fear memories to fluctuations in hippocampal neurogenesis...
March 28, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29410218/cholinergic-neurons-in-medial-septum-maintain-anxiety-like-behaviors-induced-by-chronic-inflammatory-pain
#10
Ying-Ying Jiang, Yu Zhang, Shuang Cui, Feng-Yu Liu, Ming Yi, You Wan
Cholinergic neurons in the medial septum (MS) participate in various cognitive and emotional behaviors, including innate anxiety. Chronic pain involves perceptual, cognitive and emotional components. Whether MS cholinergic system modulates pain-induced anxiety and the underlying neural circuits are involved remain unclear. In the present study, we showed that chemogenetic (DREADD) inhibition of MS cholinergic neurons relieved pain-induced anxiety-like behaviors in open field and elevated plus maze tests. Inhibiting the MS-rostral anterior cingulate cortex (rACC), but not the MS-ventral hippocampal CA1 pathway, achieved anxiolysis...
April 3, 2018: Neuroscience Letters
https://www.readbyqxmd.com/read/29338070/the-use-of-chemogenetics-in-behavioural-neuroscience-receptor-variants-targeting-approaches-and-caveats
#11
REVIEW
Erin J Campbell, Nathan J Marchant
The last decade has seen major advances in neuroscience tools allowing us to selectively modulate cellular pathways in freely moving animals. Chemogenetic approaches such as designer receptors exclusively activated by designer drugs (DREADDs) permit the remote control of neuronal function by systemic drug administration. These approaches have dramatically advanced our understanding of the neural control of behaviour. Here, we review the different techniques and genetic approaches available for the restriction of chemogenetic receptors to defined neuronal populations...
April 2018: British Journal of Pharmacology
https://www.readbyqxmd.com/read/29317484/chemogenetic-excitation-of-accumbens-projecting-infralimbic-cortical-neurons-blocks-toluene-induced-conditioned-place-preference
#12
Wesley N Wayman, John J Woodward
Abuse rates for inhalants among adolescents continue to be high, yet preclinical models for studying mechanisms underlying inhalant abuse remain limited. Our laboratory has previously shown that, in male rats, an acute binge-like exposure to toluene vapor that mimics human solvent abuse modifies the intrinsic excitability of mPFC pyramidal neurons projecting to the NAc. These changes showed region (infralimbic; IL vs prelimbic; PRL), layer (shallow; 2/3 vs deep; 5/6), target (core vs shell), and age (adolescent vs adult) dependent differences (Wayman and Woodward, 2017)...
February 7, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29191752/the-use-of-chemogenetic-approaches-to-study-the-physiological-roles-of-muscarinic-acetylcholine-receptors-in-the-central-nervous-system
#13
REVIEW
Sophie J Bradley, Andrew B Tobin, Rudi Prihandoko
Chemical genetic has played an important role in linking specific G protein-coupled receptor (GPCR) signalling to cellular processes involved in central nervous system (CNS) functions. Key to this approach has been the modification of receptor properties such that receptors no longer respond to endogenous ligands but rather can be activated selectively by synthetic ligands. Such modified receptors have been called Receptors Activated Solely by Synthetic Ligands (RASSLs) or Designer Receptors Exclusively Activated by Designer Drugs (DREADDs)...
November 27, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/29153928/enhancing-excitability-of-dopamine-neurons-promotes-motivational-behaviour-through-increased-action-initiation
#14
Linde Boekhoudt, Ellen C Wijbrans, Jodie H K Man, Mieneke C M Luijendijk, Johannes W de Jong, Geoffrey van der Plasse, Louk J M J Vanderschuren, Roger A H Adan
Motivational deficits are a key symptom in multiple psychiatric disorders, including major depressive disorder, schizophrenia and addiction. A likely neural substrate for these motivational deficits is the brain dopamine (DA) system. In particular, DA signalling in the nucleus accumbens, which originates from DA neurons in the ventral tegmental area (VTA), has been identified as a crucial substrate for effort-related and activational aspects of motivation. Unravelling how VTA DA neuronal activity relates to motivational behaviours is required to understand how motivational deficits in psychiatry can be specifically targeted...
January 2018: European Neuropsychopharmacology: the Journal of the European College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/29069598/brain-wide-mapping-of-endogenous-serotonergic-transmission-via-chemogenetic-fmri
#15
Andrea Giorgi, Sara Migliarini, Alberto Galbusera, Giacomo Maddaloni, Maddalena Mereu, Giulia Margiani, Marta Gritti, Silvia Landi, Francesco Trovato, Sine Mandrup Bertozzi, Andrea Armirotti, Gian Michele Ratto, Maria Antonietta De Luca, Raffaella Tonini, Alessandro Gozzi, Massimo Pasqualetti
Serotonin-producing neurons profusely innervate brain regions via long-range projections. However, it remains unclear whether and how endogenous serotonergic transmission specifically influences regional or global functional activity. We combined designed receptors exclusively activated by designed drugs (DREADD)-based chemogenetics and functional magnetic resonance imaging (fMRI), an approach we term "chemo-fMRI," to causally probe the brain-wide substrates modulated by endogenous serotonergic activity...
October 24, 2017: Cell Reports
https://www.readbyqxmd.com/read/29053824/chemogenetic-locus-coeruleus-activation-restores-reversal-learning-in-a-rat-model-of-alzheimer-s-disease
#16
Jacki M Rorabaugh, Termpanit Chalermpalanupap, Christian A Botz-Zapp, Vanessa M Fu, Natalie A Lembeck, Robert M Cohen, David Weinshenker
See Grinberg and Heinsen (doi:10.1093/brain/awx261) for a scientific commentary on this article. Clinical evidence suggests that aberrant tau accumulation in the locus coeruleus and noradrenergic dysfunction may be a critical early step in Alzheimer’s disease progression. Yet, an accurate preclinical model of these phenotypes that includes early pretangle tau accrual in the locus coeruleus, loss of locus coeruleus innervation and deficits locus coeruleus/norepinephrine modulated behaviours, does not exist, hampering the identification of underlying mechanisms and the development of locus coeruleus-based therapies...
November 1, 2017: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/29042322/activation-of-parvalbumin-neurons-in-the-rostro-dorsal-sector-of-the-thalamic-reticular-nucleus-promotes-sensitivity-to-pain-in-mice
#17
Jing Liu, Meng-Qi Zhang, Xu Wu, Michael Lazarus, Yoan Cherasse, Mao-Yun Yuan, Zhi-Li Huang, Rui-Xi Li
The calcium-binding protein, parvalbumin (PV), is highly expressed in thalamic reticular nucleus (TRN) GABAergic neurons, which receive input from the cerebral cortex and thalamus and send inhibitory output to the thalamic relay nucleus. Previous studies suggest that the TRN is involved in pain regulation as an important relay nucleus of the ascending pain pathway. However, little is known about its functional role in pain regulation and interconnectivity. In our study, the role of rostro-dorsal sector of TRN (TRNrd) PV-positive neurons in pain regulation was studied using chemogenetics based on designer receptors exclusively activated by designer drugs (DREADD)...
October 16, 2017: Neuroscience
https://www.readbyqxmd.com/read/29037828/chemogenetic-modulation-of-cholinergic-interneurons-reveals-their-regulating-role-on-the-direct-and-indirect-output-pathways-from-the-striatum
#18
Patrick Aldrin-Kirk, Andreas Heuer, Daniella Rylander Ottosson, Marcus Davidsson, Bengt Mattsson, Tomas Björklund
The intricate balance between dopaminergic and cholinergic neurotransmission in the striatum has been thoroughly difficult to characterize. It was initially described as a seesaw with a competing function of dopamine versus acetylcholine. Recent technical advances however, have brought this view into question suggesting that the two systems work rather in concert with the cholinergic interneurons (ChIs) driving dopamine release. In this study, we have utilized two transgenic Cre-driver rat lines, a choline acetyl transferase ChAT-Cre transgenic rat and a novel double-transgenic tyrosine hydroxylase TH-Cre/ChAT-Cre rat to further elucidate the role of striatal ChIs in normal motor function and in Parkinson's disease...
October 14, 2017: Neurobiology of Disease
https://www.readbyqxmd.com/read/28912160/dopamine-d2-receptors-modulate-pyramidal-neurons-in-mouse-medial-prefrontal-cortex-through-a-stimulatory-g-protein-pathway
#19
Sarah E Robinson, Vikaas S Sohal
Dopaminergic modulation of prefrontal cortex (PFC) is thought to play key roles in many cognitive functions and to be disrupted in pathological conditions, such as schizophrenia. We have previously described a phenomenon whereby dopamine D2 receptor (D2R) activation elicits afterdepolarizations (ADPs) in subcortically projecting (SC) pyramidal neurons within L5 of the PFC. These D2R-induced ADPs only occur following synaptic input, which activates NMDARs, even when the delay between the synaptic input and ADPs is relatively long (e...
October 18, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28794102/optogenetics-and-pharmacogenetics-principles-and-applications
#20
REVIEW
Jingwei Jiang, Huxing Cui, Kamal Rahmouni
Remote and selective spatiotemporal control of the activity of neurons to regulate behavior and physiological functions has been a long-sought goal in system neuroscience. Identification and subsequent bioengineering of light-sensitive ion channels (e.g., channelrhodopsins, halorhodopsin, and archaerhodopsins) from the bacteria have made it possible to use light to artificially modulate neuronal activity, namely optogenetics. Recent advance in genetics has also allowed development of novel pharmacological tools to selectively and remotely control neuronal activity using engineered G protein-coupled receptors, which can be activated by otherwise inert drug-like small molecules such as the designer receptors exclusively activated by designer drug, a form of chemogenetics...
December 1, 2017: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
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