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https://www.readbyqxmd.com/read/29053824/chemogenetic-locus-coeruleus-activation-restores-reversal-learning-in-a-rat-model-of-alzheimer-s-disease
#1
Jacki M Rorabaugh, Termpanit Chalermpalanupap, Christian A Botz-Zapp, Vanessa M Fu, Natalie A Lembeck, Robert M Cohen, David Weinshenker
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...
September 25, 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
#2
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 14, 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
#3
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 13, 2017: Neurobiology of Disease
https://www.readbyqxmd.com/read/29027903/functional-dichotomy-in-spinal-vs-prefrontal-projecting-locus-coeruleus-modules-splits-descending-noradrenergic-analgesia-from-ascending-aversion-and-anxiety-in-rats
#4
Stefan Hirschberg, Yong Li, Andrew Randall, Eric J Kremer, Anthony E Pickering
The locus coeruleus (LC) projects throughout the brain and spinal cord and is the major source of central noradrenaline. It remains unclear whether the LC acts functionally as a single global effector or as discrete modules. Specifically, while spinal-projections from LC neurons can exert analgesic actions, it is not known whether they can act independently of ascending LC projections. Using viral vectors taken up at axon terminals, we expressed chemogenetic actuators selectively in LC neurons with spinal (LC:(SC)) or prefrontal cortex (LC:(PFC)) projections...
October 13, 2017: ELife
https://www.readbyqxmd.com/read/29022877/striatal-adenosine-a2a-receptor-neurons-control-active-period-sleep-via-parvalbumin-neurons-in-external-globus-pallidus
#5
Xiang-Shan Yuan, Lu Wang, Hui Dong, Wei-Min Qu, Su-Rong Yang, Yoan Cherasse, Michael Lazarus, Serge N Schiffmann, Alban de Kerchove d'Exaerde, Rui-Xi Li, Zhi-Li Huang
Dysfunction of the striatum is frequently associated with sleep disturbances. However, its role in sleep-wake regulation has been paid little attention even though the striatum densely expresses adenosine A2A receptors (A2ARs), which are essential for adenosine-induced sleep. Here we showed that chemogenetic activation of A2AR neurons in specific subregions of the striatum induced a remarkable increase in non-rapid eye movement (NREM) sleep. Anatomical mapping and immunoelectron microscopy revealed that striatal A2AR neurons innervated the external globus pallidus (GPe) in a topographically organized manner and preferentially formed inhibitory synapses with GPe parvalbumin (PV) neurons...
October 12, 2017: ELife
https://www.readbyqxmd.com/read/28993631/establishment-of-a-repeated-social-defeat-stress-model-in-female-mice
#6
Aki Takahashi, Jia-Ru Chung, Song Zhang, Hongxing Zhang, Yael Grossman, Hossein Aleyasin, Meghan E Flanigan, Madeline L Pfau, Caroline Menard, Dani Dumitriu, Georgia E Hodes, Bruce S McEwen, Eric J Nestler, Ming-Hu Han, Scott J Russo
Numerous studies have employed repeated social defeat stress (RSDS) to study the neurobiological mechanisms of depression in rodents. An important limitation of RSDS studies to date is that they have been conducted exclusively in male mice due to the difficulty of initiating attack behavior directed toward female mice. Here, we establish a female mouse model of RSDS by inducing male aggression toward females through chemogenetic activation of the ventrolateral subdivision of the ventromedial hypothalamus (VMHvl)...
October 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28969393/chemogenetic-management-of-neuropathic-pain
#7
Allan Basbaum
No abstract text is available yet for this article.
October 1, 2017: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/28967909/cellular-and-oscillatory-substrates-of-fear-extinction-learning
#8
Patrick Davis, Yosif Zaki, Jamie Maguire, Leon G Reijmers
The mammalian brain contains dedicated circuits for both the learned expression and suppression of fear. These circuits require precise coordination to facilitate the appropriate expression of fear behavior, but the mechanisms underlying this coordination remain unclear. Using a combination of chemogenetics, activity-based neuronal-ensemble labeling and in vivo electrophysiology, we found that fear extinction learning confers on parvalbumin-expressing (PV) interneurons in the basolateral amygdala (BLA) a dedicated role in the selective suppression of a previously encoded fear memory and BLA fear-encoding neurons...
October 2, 2017: Nature Neuroscience
https://www.readbyqxmd.com/read/28963505/slow-wave-sleep-is-controlled-by-a-subset-of-nucleus-accumbens-core-neurons-in-mice
#9
Yo Oishi, Qi Xu, Lu Wang, Bin-Jia Zhang, Koji Takahashi, Yohko Takata, Yan-Jia Luo, Yoan Cherasse, Serge N Schiffmann, Alban de Kerchove d'Exaerde, Yoshihiro Urade, Wei-Min Qu, Zhi-Li Huang, Michael Lazarus
Sleep control is ascribed to a two-process model, a widely accepted concept that posits homoeostatic drive and a circadian process as the major sleep-regulating factors. Cognitive and emotional factors also influence sleep-wake behaviour; however, the precise circuit mechanisms underlying their effects on sleep control are unknown. Previous studies suggest that adenosine has a role affecting behavioural arousal in the nucleus accumbens (NAc), a brain area critical for reinforcement and reward. Here, we show that chemogenetic or optogenetic activation of excitatory adenosine A2A receptor-expressing indirect pathway neurons in the core region of the NAc strongly induces slow-wave sleep...
September 29, 2017: Nature Communications
https://www.readbyqxmd.com/read/28960802/functional-role-for-suppression-of-the-insular-striatal-circuit-in-modulating-interoceptive-effects-of-alcohol
#10
Anel A Jaramillo, Verda E Agan, Viren H Makhijani, Stephen Pedroza, Zoe A McElligott, Joyce Besheer
The insular cortex (IC) is a region proposed to modulate, in part, interoceptive states and motivated behavior. Interestingly, IC dysfunction and deficits in interoceptive processing are often found among individuals with substance-use disorders. Furthermore, the IC projects to the nucleus accumbens core (AcbC), a region known to modulate the discriminative stimulus/interoceptive effects of alcohol and other drug-related behaviors. Therefore, the goal of the present work was to investigate the possible role of the IC ➔ AcbC circuit in modulating the interoceptive effects of alcohol...
September 27, 2017: Addiction Biology
https://www.readbyqxmd.com/read/28960176/parvalbumin-positive-interneurons-mediate-cortical-hippocampal-interactions-that-are-necessary-for-memory-consolidation
#11
Frances Xia, Blake A Richards, Matthew M Tran, Sheena A Josselyn, Kaori Takehara-Nishiuchi, Paul W Frankland
Following learning, increased coupling between spindle oscillations in the medial prefrontal cortex (mPFC) and ripple oscillations in the hippocampus is thought to underlie memory consolidation. However, whether learning-induced increases in ripple-spindle coupling are necessary for successful memory consolidation has not been tested directly. In order to decouple ripple-spindle oscillations, here we chemogenetically inhibited parvalbumin-positive (PV(+)) interneurons, since their activity is important for regulating the timing of spiking activity during oscillations...
September 29, 2017: ELife
https://www.readbyqxmd.com/read/28939475/investigating-the-transition-from-recent-to-remote-memory-using-advanced-tools
#12
REVIEW
Adi Doron, Inbal Goshen
Remote memories, weeks to decades long, are usually the ones most important to the organism, as the longevity of a memory is tightly connected to its significance. Retrograde amnesia studies in human patients as well as lesions and immediate early gene expression investigation in animal models, suggested that the hippocampus has a time dependent role in memory consolidation. Namely, that as a memory matures it becomes independent of the hippocampus and instead depends on extra-hippocampal areas. However, accumulating evidence implies that this temporal segregation is not as rigid as originally proposed...
September 20, 2017: Brain Research Bulletin
https://www.readbyqxmd.com/read/28912554/oxytocin-stimulates-hippocampal-neurogenesis-via-oxytocin-receptor-expressed-in-ca3-pyramidal-neurons
#13
Yu-Ting Lin, Chien-Chung Chen, Chiung-Chun Huang, Katsuhiko Nishimori, Kuei-Sen Hsu
In addition to the regulation of social and emotional behaviors, the hypothalamic neuropeptide oxytocin has been shown to stimulate neurogenesis in adult dentate gyrus; however, the mechanisms underlying the action of oxytocin are still unclear. Taking advantage of the conditional knockout mouse model, we show here that endogenous oxytocin signaling functions in a non-cell autonomous manner to regulate survival and maturation of newly generated dentate granule cells in adult mouse hippocampus via oxytocin receptors expressed in CA3 pyramidal neurons...
September 14, 2017: Nature Communications
https://www.readbyqxmd.com/read/28912160/dopamine-d2-receptors-modulate-pyramidal-neurons-in-mouse-medial-prefrontal-cortex-through-a-stimulatory-g-protein-pathway
#14
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/28910619/loss-of-hyperdirect-pathway-cortico-subthalamic-inputs-following-degeneration-of-midbrain-dopamine-neurons
#15
Hong-Yuan Chu, Eileen L McIver, Ryan F Kovaleski, Jeremy F Atherton, Mark D Bevan
The motor symptoms of Parkinson's disease (PD) are linked to abnormally correlated and coherent activity in the cortex and subthalamic nucleus (STN). However, in parkinsonian mice we found that cortico-STN transmission strength had diminished by 50%-75% through loss of axo-dendritic and axo-spinous synapses, was incapable of long-term potentiation, and less effectively patterned STN activity. Optogenetic, chemogenetic, genetic, and pharmacological interrogation suggested that downregulation of cortico-STN transmission in PD mice was triggered by increased striato-pallidal transmission, leading to disinhibition of the STN and increased activation of STN NMDA receptors...
September 13, 2017: Neuron
https://www.readbyqxmd.com/read/28883753/inhibition-of-anterior-cingulate-cortex-excitatory-neuronal-activity-induces-conditioned-place-preference-in-a-mouse-model-of-chronic-inflammatory-pain
#16
Sukjae Joshua Kang, Siyong Kim, Jaehyun Lee, Chuljung Kwak, Kyungmin Lee, Min Zhuo, Bong-Kiun Kaang
The anterior cingulate cortex (ACC) is known for its role in perception of nociceptive signals and the associated emotional responses. Recent optogenetic studies, involving modulation of neuronal activity in the ACC, show that the ACC can modulate mechanical hyperalgesia. In the present study, we used optogenetic techniques to selectively modulate excitatory pyramidal neurons and inhibitory interneurons in the ACC in a model of chronic inflammatory pain to assess their motivational effect in the conditioned place preference (CPP) test...
September 2017: Korean Journal of Physiology & Pharmacology
https://www.readbyqxmd.com/read/28883467/tanycytes-control-the-hormonal-output-of-the-hypothalamic-pituitary-thyroid-axis
#17
Helge Müller-Fielitz, Marcus Stahr, Mareike Bernau, Marius Richter, Sebastian Abele, Victor Krajka, Anika Benzin, Jan Wenzel, Kathrin Kalies, Jens Mittag, Heike Heuer, Stefan Offermanns, Markus Schwaninger
The hypothalamic-pituitary-thyroid (HPT) axis maintains circulating thyroid hormone levels in a narrow physiological range. As axons containing thyrotropin-releasing hormone (TRH) terminate on hypothalamic tanycytes, these specialized glial cells have been suggested to influence the activity of the HPT axis, but their exact role remained enigmatic. Here, we demonstrate that stimulation of the TRH receptor 1 increases intracellular calcium in tanycytes of the median eminence via Gαq/11 proteins. Activation of Gαq/11 pathways increases the size of tanycyte endfeet that shield pituitary vessels and induces the activity of the TRH-degrading ectoenzyme...
September 7, 2017: Nature Communications
https://www.readbyqxmd.com/read/28882425/presence-of-pups-suppresses-hunger-induced-feeding-in-virgin-adult-mice-of-both-sexes
#18
Ying Han, Xing-Yu Li, Shao-Ran Wang, Yi-Chao Wei, Xiao-Hong Xu
Despite recent progress on neural pathways underlying individual behaviors, how an animal balances and prioritizes behavioral outputs remains poorly understood. While studying the relationship between hunger-induced feeding and pup-induced maternal behaviors in virgin female mice, we made the unexpected discovery that presence of pups strongly delayed and decreased food consumption. Strikingly, presence of pups also suppressed feeding induced by optogenetic activation of Agrp neurons. Such a suppressive effect inversely correlated with the extents of maternal behaviors, but did not rely on the display of these behaviors, and was also present in virgin males...
September 4, 2017: Neuroscience
https://www.readbyqxmd.com/read/28877477/heparin-increases-food-intake-through-agrp-neurons
#19
Canjun Zhu, Pingwen Xu, Yanlin He, Yexian Yuan, Tao Wang, Xingcai Cai, Lulu Yu, Liusong Yang, Junguo Wu, Lina Wang, Xiaotong Zhu, Songbo Wang, Ping Gao, Qianyun Xi, Yongliang Zhang, Yong Xu, Qingyan Jiang, Gang Shu
Although the widely used anticoagulant drug heparin has been shown to have many other biological functions independent of its anticoagulant role, its effects on energy homeostasis are unknown. Here, we demonstrate that heparin level is negatively associated with nutritional states and that heparin treatment increases food intake and body weight gain. By using electrophysiological, pharmacological, molecular biological, and chemogenetic approaches, we provide evidence that heparin increases food intake by stimulating AgRP neurons and increasing AgRP release...
September 5, 2017: Cell Reports
https://www.readbyqxmd.com/read/28871962/aversive-stimuli-drive-hypothalamus-to-habenula-excitation-to-promote-escape-behavior
#20
Salvatore Lecca, Frank Julius Meye, Massimo Trusel, Anna Tchenio, Julia Harris, Martin Karl Schwarz, Denis Burdakov, Francois Georges, Manuel Mameli
A sudden aversive event produces escape behaviors, an innate response essential for survival in virtually all-animal species. Nuclei including the lateral habenula (LHb), the lateral hypothalamus (LH), and the midbrain are not only reciprocally connected, but also respond to negative events contributing to goal-directed behaviors. However, whether aversion encoding requires these neural circuits to ultimately prompt escape behaviors remains unclear. We observe that aversive stimuli, including foot-shocks, excite LHb neurons and promote escape behaviors in mice...
September 5, 2017: ELife
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