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chemogenetics dreadds

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
J Stedehouder, D Brizee, G Shpak, S A Kushner
Axonal myelination of neocortical pyramidal neurons is dynamically modulated 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 utilized cell-type specific Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) in adult male and female mice to activate a sparse population of medial prefrontal cortex PV+ interneurons...
March 5, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
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 (A2aRs). 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
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
Aijing Gao, Frances Xia, Axel 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...
February 16, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
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...
February 1, 2018: Neuroscience Letters
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...
January 16, 2018: British Journal of Pharmacology
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 lab 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 medial prefrontal cortex (mPFC) pyramidal neurons projecting to the nucleus accumbens (NAc). These changes showed region (infralimbic; IL vs. prelimbic; PRL), layer (shallow; 2/3 vs. deep; 5/6), target (core vs...
January 9, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
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
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...
November 16, 2017: European Neuropsychopharmacology: the Journal of the European College of Neuropsychopharmacology
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
Jacki M Rorabaugh, Termpanit Chalermpalanupap, Christian A Botz-Zapp, Vanessa M Fu, Natalie A Lembeck, Robert M Cohen, David Weinshenker
No abstract text is available yet for this article.
November 1, 2017: Brain: a Journal of Neurology
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
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
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
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
Juan L Gomez, Jordi Bonaventura, Wojciech Lesniak, William B Mathews, Polina Sysa-Shah, Lionel A Rodriguez, Randall J Ellis, Christopher T Richie, Brandon K Harvey, Robert F Dannals, Martin G Pomper, Antonello Bonci, Michael Michaelides
The chemogenetic technology DREADD (designer receptors exclusively activated by designer drugs) is widely used for remote manipulation of neuronal activity in freely moving animals. DREADD technology posits the use of "designer receptors," which are exclusively activated by the "designer drug" clozapine N-oxide (CNO). Nevertheless, the in vivo mechanism of action of CNO at DREADDs has never been confirmed. CNO does not enter the brain after systemic drug injections and shows low affinity for DREADDs. Clozapine, to which CNO rapidly converts in vivo, shows high DREADD affinity and potency...
August 4, 2017: Science
Carolyn Arico, Elena E Bagley, Pascal Carrive, Neda Assareh, Gavan P McNally
The midbrain periaqueductal gray (PAG) has been implicated in the generation and transmission of a prediction error signal that instructs amygdala-based fear and extinction learning. However, the PAG also plays a key role in the expression of conditioned fear responses. The evidence for a role of the PAG in fear learning and extinction learning has been obtained almost exclusively using PAG-dependent fear responses. It is less clear whether the PAG regulates fear learning when other measures of learned fear are used...
July 14, 2017: Neurobiology of Learning and Memory
Keisuke Koga, Kensho Kanehisa, Yuta Kohro, Miho Shiratori-Hayashi, Hidetoshi Tozaki-Saitoh, Kazuhide Inoue, Hidemasa Furue, Makoto Tsuda
Inhibitory interneurons in the spinal dorsal horn (SDH) are crucial for processing somatosensory information originating in the periphery. However, the effects of the acute and selective inactivation of GABAergic SDH interneurons on pain processing are not fully understood. In this study, we used designer receptors exclusively activated by designer drugs (DREADD) technology and vesicular GABA transporter-Cre (Vgat-Cre) mice to selectively express a modified human muscarinic Gi protein-coupled receptor (hM4Di) in Vgat-Cre (+) GABAergic SDH interneurons in the fourth lumbar segment...
July 5, 2017: Scientific Reports
Elizabeth A McCarthy, Arman Maqsudlu, Matthew Bass, Sofia Georghiou, James A Cherry, Michael J Baum
Sexually naïve estrous female mice seek out male urinary pheromones; however, they initially display little receptive (lordosis) behavior in response to male mounts. Vomeronasal-accessory olfactory bulb inputs to the medial amygdala (Me) regulate courtship in female rodents. We used a reversible inhibitory chemogenetic technique (Designer Receptors Exclusively Activated by Designer Drugs; DREADDs) to assess the contribution of Me signaling to females' preference for male pheromones and improvement in receptivity normally seen with repeated testing...
August 2017: European Journal of Neuroscience
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