Must-Read Neural Circuit Research Papers in July 2018

Neurodegenerative Motor Disorders

We’ve compiled our latest list of the neural circuit research papers published in July with relevance and interest to the Inscopix Community. They include several resource-oriented papers like simultaneous optogenetics and calcium imaging during free behavior, genetically-encoded fluorescent indicators for dopamine, and new calcium sensors, etc., all validated during in vivo behaviors. We include papers looking at motivated behaviors, emotional states, feeding, plus there’s a blockbuster paper on the neural circuits of direction selectivity in ferret visual cortex. Happy reading!

1. Simultaneous Optogenetics and Cellular Resolution Calcium Imaging During Active Behavior Using a Miniaturized Microscope by Alice M. Stamatakis, Mike J. Schachter, Srishti Gulati, Kevin T. Zitelli, Sam Malanowski, Arash Tajik, Christopher Fritz, Mark Trulson and Stephani L. Otte. Frontiers in Neuroscience.

They use nVoke, an integrated one-photon cellular-resolution Ca2+ imaging & optogenetic system to investigate the causal link between the basolateral amygdala to nucleus accumbens circuit in freely-behaving mice. The ability to perform optogenetics and Ca2+ imaging in the same field of view opens up possibilities to test sophisticated causal hypotheses that link neural circuit dynamics with behavior, system states, and plasticity.

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2. Dopamine neurons create Pavlovian conditioned stimuli with circuit-defined motivational properties by Benjamin T. Saunders, Jocelyn M. Richard, Elyssa B. Margolis & Patricia H. Janak. Nature Neuroscience.

This is a cool paper in which they trained rats to associate sensory cues with optogenetic activation of dopamine neurons, resulting in both conditioned dopamine neuron activity and conditioned behaviors that varied according to which dopamine neuron subpopulation was targeted. They were able to tease apart the function of dopamine neurons in Pavlovian conditioned motivation, showing ventral tegmental area-associated cues acquire incentive motivational value, and substantia nigra pars compacta-associated cues invigorate intense locomotion. Furthermore, they found that nucleus accumbens (NAc) core-projecting dopamine neurons, but not NAc shell-projecting dopamine neurons, mediate the acquisition of incentive value. According to the authors, “incentive value here is defined as that property of cues that lends them motivational power to attract attention and become desirable in the absence of reward, an important process that may contribute to compulsive seeking in addiction.”.

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3. Parallel circuits from the bed nuclei of stria terminalis to the lateral hypothalamus drive opposing emotional states by William J. Giardino, Ada Eban-Rothschild, Daniel J. Christoffel, Shi-Bin Li, Robert C. Malenka & Luis de Lecea. Nature Neuroscience.

In this in vivo study, they provide the first functional characterization of two distinct neuropeptide-defined (corticotropin-releasing factor, and cholecystokinin) GABAergic BNST (bed nuclei of stria terminalis) subpopulations. Their findings provide a mechanistic framework for BNST→LH (Lateral hypothalamus) circuit dysregulations in psychiatric disorders.

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4. Nicotine aversion is mediated by GABAergic interpeduncular nucleus inputs to laterodorsal tegmentum by Shannon L. Wolfman, Daniel F. Gill, Fili Bogdanic, Katie Long, Ream Al-Hasani, Jordan G. McCall, Michael R. Bruchas & Daniel S. McGehee. Nature Communications.

They identified and clarified the nature of an inhibitory IPN (interpeduncular nucleus) projection to the LDTg (laterodorsal tegmentum) and demonstrated its behavioral relevance by showing the modulation of IPN→ LCTg can shift the balance between reward and aversion, supporting the larger hypothesis that aversion can regulate nicotine-related behaviors.

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5. A Genetically Encoded Fluorescent Sensor Enables Rapid and Specific Detection of Dopamine in Flies, Fish, and Mice by Fangmiao Sun, Jianzhi Zeng, Miao Jing, Jingheng Zhou, Jiesi Feng, Scott F. Owen, Yichen Luo, Funing Li, Huan Wang, Takashi Yamaguchi, Zihao Yong, Yijing Gao, Wanling Peng, Lizhao Wang, Siyu Zhang, Jiulin Du, Dayu Lin, Min Xu, Anatol C. Kreitzer, Guohong Cui, Yulong Li. Cell.

GRABDA sensors are genetically encoded dopamine (DA) sensors based on GPCR. GRABDA enables fast, sensitive DA detection with molecular and cellular specificity. Two separate constructs expand the effective dynamic range of DA detection. They demonstrate efficacy in multiple species and behaviors, and even noted some novel behavioral results.

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6. A Suite of Transgenic Driver and Reporter Mouse Lines with Enhanced Brain-Cell-Type Targeting and Functionality by Tanya L. Daigle, Linda Madisen, Travis A. Hage, Matthew T. Valley, Ulf Knoblich, Rylan S. Larsen, Marc M. Takeno, Lawrence Huang, Hong Gu, Rachael Larsen, Maya Mills, Alice Bosma-Moody, La’ Akea Siverts, Miranda Walker, Lucas T. Graybuck, Zizhen Yao, Olivia Fong, Thuc Nghi Nguyen, Emma Garren, Garreck H. Lenz, Mariya Chavarha, Julie Pendergraft, James Harrington, Karla E. Hirokawa, Julie A. Harris, Philip R. Nicovich, Medea J. McGraw, Douglas R. Ollerenshaw, Kimberly A. Smith, Christopher A. Baker, Jonathan T. Ting, Susan M. Sunkin, Jérôme Lecoq, Michael Z. Lin, Edward S. Boyden, Gabe J. Murphy, Nuno M. da Costa, Jack Waters, Lu Li, Bosiljka Tasic, Hongkui Zeng. Cell.

In this amazing resource, they develop and characterize 23 new driver lines and 26 new reporter lines for a wide range of applications, like calcium sensors, voltage sensors, opsins, etc. They functionally characterize the new calcium reporters.

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7. Differential tuning of excitation and inhibition shapes direction selectivity in ferret visual cortex by Daniel E. Wilson, Benjamin Scholl & David Fitzpatrick. Nature.

In a tour de force, they use a combination of techniques including in vivo whole-cell recording, synaptic- and cellular-resolution in vivo two-photon calcium imaging, and GABA (γ-aminobutyric acid) neuron-selective optogenetic manipulation to dissect the factors that contribute to the direction-selective responses of layer 2/3 neurons in ferret visual cortex (V1). Their findings suggest that selective responses of visual cortical neurons are built with a broadly tuned palette of excitatory synaptic inputs that is further refined by enhancing responses to the preferred stimulus and suppressing responses to non-preferred stimuli.

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8. A Neural Circuit Underlying the Generation of Hot Flushes by Stephanie L. Padilla, Christopher W. Johnson, Forrest D. Barker, Michael A. Patterson, Richard D. Palmiter. Cell Reports.

Highlights: 1) Activation of Kiss1ARH neurons evokes a hot flush-like response in mice. 2) Ovariectomy sensitizes the hot flush response of Kiss1ARH neurons. 3) Kiss1ARH transmission to the preoptic area (POA) is sufficient to evoke a hot flush. 4) Neurokinin B signaling in the POA is required for a hot flush

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9. Encoding of Conditioned Taste Aversion in Cortico-Amygdala Circuits by Karen Lavi, Gilad A. Jacobson, Kobi Rosenblum, Andreas Lüthi. Cell Reports.

Highlights: 1) Conditioned taste aversion (CTA) leads to re-mapping in the gustatory cortex (GC). 2) Neuronal responses to conditioned tastants resemble those to innately aversive tastants. 3) Conditioned tastants evoke larger responses compared to innately aversive tastants

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10. Regulation of feeding by somatostatin neurons in the tuberal nucleus by Sarah Xinwei Luo, Ju Huang, Qin Li, Hasan Mohammad, Chun-Yao Lee, Kumar Krishna, Alison Maun-Yeng Kok, Yu Lin Tan, Joy Yi Lim, Hongyu Li, Ling Yun Yeow, Jingjing Sun, Miao He, Joanes Grandjean, Sreedharan Sajikumar, Weiping Han, Yu Fu. Science.

“Luo et al. found that GABAergic somatostatin neurons in the tuberal nucleus are functionally involved in the regulation of feeding in mice (GABA, γ-aminobutyric acid) (see the Perspective by Diano). These neurons were activated by food deprivation or hunger hormone. Loss- and gain-of-function experiments indicated that these cells are necessary and sufficient to control systemic metabolic balance. This newly described regulatory center is extensively connected with other feeding control circuits via projections to other hypothalamic nuclei.”

Read more here and here

11. Nucleus Accumbens Microcircuit Underlying D2-MSN-Driven Increase in Motivation by Carina Soares-Cunha, Bárbara Coimbra, Ana Verónica Domingues, Nivaldo Vasconcelos, Nuno Sousa and Ana João Rodrigues. eNeuro.

“The nucleus accumbens (NAc) is a key brain region of the reward system and is crucial for motivation. We showed that activation of NAc D2-expressing neurons enhances motivation by modulating VTA dopaminergic activity via ventral pallidum inhibition. The behavioural effect was dependent on local cholinergic-dependent dopamine release by VTA terminals that required D1 and D2 dopamine receptors in the NAc.”

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