It’s the first must-read list for neural circuit research articles in 2018, and the line-up of papers include work on circuits coding for movements to fear and anxiety. Four publications last month used Inscopix nVista technology! Happy reading!
1. Dopamine neuron activity before action initiation gates and invigorates future movements by Joaquim Alves da Silva, Fatuel Tecuapetla, Vitor Paixão & Rui M. Costa. Nature.
They see a burst of dopamine levels at the beginning of a movement only, as opposed to all the time, and show this is critical for movement initiation. Moreover, brief activation of dopamine neurons when mice were immobile increased the probability and vigor of future movements. They use Inscopix nVista imaging to show that substantia nigra pars compacta dopamine neurons are transiently active at sequence initiation, and when inhibited with optogenetics, impair sequence initiation, but not sequence performance. This has important implications for understanding Parkinson's disease.
2. Midbrain circuits that set locomotor speed and gait selection by V. Caggiano, R. Leiras, H. Goñi-Erro, D. Masini, C. Bellardita, J. Bouvier, V. Caldeira, G. Fisone & O. Kiehn. Nature
Midbrain 'Start neurons' are essential to take the first step to initiate locomotion and control the speed. Here’s another paper with important implications for Parkinson’s disease.
3. Nucleus Accumbens Subnuclei Regulate Motivated Behavior via Direct Inhibition and Disinhibition of VTA Dopamine Subpopulations by Hongbin Yang, Johannes W. de Jong, YeEun Tak, James Peck, Helen S. Bateup, Stephan Lammel. Neuron.
“How do nucleus accumbens (NAc) subdivisions shape information flow into distinct ventral tegmental area (VTA) subcircuits? Yang et al. (2018) provide insightful answers to this question by expanding our knowledge about the circuit architecture and function of reciprocal connectivity between NAc and VTA”
4. A Non-canonical Reticular-Limbic Central Auditory Pathway via Medial Septum Contributes to Fear Conditioning by Guang-Wei Zhang, Wen-Jian Sun, Brian Zingg, Li Shen, Jufang He, Ying Xiong, Huizhong W. Tao, Li I. Zhang. Neuron.
They study a previously unrecognized central auditory pathway involved in processing aversive acoustic signals that contributes to auditory fear conditioning. This has implications for understanding how auditory information is processed in the brain.
Read more here
5. Anxiety Cells in a Hippocampal-Hypothalamic Circuit
by Jessica C. Jimenez, Katy Su, Alexander R. Goldberg, Victor M. Luna, Jeremy S. Biane, Gokhan Ordek, Pengcheng Zhou, Samantha K. Ong, Matthew A. Wright, Larry Zweifel, Liam Paninski, René Hen, Mazen A. Kheirbek. Neuron.
They use Inscopix nVista technology to measure neural activity both in the dorsal and ventral hippocampus to study the specific anxiety-related circuit from the ventral hippocampus to the lateral hypothalamus. This study raises the very intriguing possibility that the hippocampus is actually hard-wired to respond to stimuli and environments that produce an innate avoidance, while others may be hard-wired to respond to appetitive stimuli and environments. It also opens up further investigation into the neural circuits carrying the valence information into, within, and out of the hippocampus.
6. Oxytocin signaling in the medial amygdala is required for sex discrimination of social cues by
Shenqin Yao, Joseph Bergan, Anne Lanjuin, Catherine Dulac. eLife.
“These results uncover the critical role of oxytocin signaling in a molecularly defined neuronal population in order to modulate the behavioral and physiological responses of male mice to females on a moment-to-moment basis.”
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7. Diversity and connectivity of layer 5 somatostatin-expressing interneurons in the mouse barrel cortex by Maximiliano José Nigro, Yoshiko Hashikawa and Bernardo Rudy. JNeurosci.
“Morphologically diverse layer 5 SST-INs show different patterns of activity in behaving animals. However, little is known about the abundance and connectivity of each morphological type and the correlation between morphological subtype and spiking properties. We demonstrate a correlation between the morphological and electrophysiological diversity of layer 5 SST-INs. Based on these findings we built a classifier to infer the abundance of each morphological subtype. Lastly, using paired recordings combined with morphological analysis, we investigated the connectivity of each morphological subtype. Our data suggest that, by targeting different cell types and cellular compartments, morphologically diverse SST-INs might gate different excitatory inputs in the mouse barrel cortex.”
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8. An insula-central amygdala circuit for guiding tastant-reinforced choice behavior by Hillary Schiff, Anna Lien Bouhuis, Kai Yu, Mario A. Penzo, Haohong Li, Miao He and Bo Li. JNeurosci.
“The ability to predict which substances are suitable for consumption and then produce an appropriate action to those substances is critical for survival. Here we found that activity in the insular cortex (IC) to central amygdala (CeA) circuit is necessary for establishing appropriate behavioral responses to taste-predicting cues. This neural circuit seems to be particularly tuned to avoid an unpleasant tastant, and is also sufficient to drive learning of such avoidance responses. These results suggest that the IC-CeA circuit is critical for generating appropriate behavioral responses when facing different choices during foraging.”
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9. Interrogating the Spatiotemporal Landscape of Neuromodulatory GPCR Signaling by Real-Time Imaging of cAMP in Intact Neurons and Circuits by Brian S. Muntean, Stefano Zucca, Courtney M. MacMullen, Maria T. Dao, Caitlin Johnston, Hideki Iwamoto, Randy D. Blakely, Ronald L. Davis, Kirill A. Martemyanov. Cell Reports.
They develop tools useful for studying the role and mechanisms of neuromodulation across various circuits and provide a foundation for uncovering the signaling characteristics of various neurotransmitters while further serving as a guide to understanding the mechanistic underpinnings of signal regulation. “The availability of this tool also simplifies avenues in FRET imaging approaches in free-moving animals through microendoscopy (Goto et al., 2015), cranial windows (Gong et al., 2014), and miniaturized microscopes.”
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10. Locus coeruleus input to hippocampal CA3 drives single-trial learning of a novel context by Akiko Wagatsuma, Teruhiro Okuyama, Chen Sun, Lillian M. Smith, Kuniya Abe, and Susumu Tonegawa. PNAS.
They have identified a brain network that allows the brain to record memories of new places. They use Inscopix nVIsta to record brain activity and show that cells reactivated in both novel and familiar contexts suppress LC inputs at the time of encoding, resulting in more variable place fields in CA3 neurons. Thus neuromodulatory input from LC to CA3 is crucial for the formation of a persistent memory in the hippocampus. “This study opens an exciting avenue of research into the circuit mechanism by which behaviorally relevant stimuli are specifically encoded into long-term memory, ensuring that important stimuli are stored preferentially over incidental ones,” said Tonegawa.
11. Organization of Valence-Encoding and Projection-Defined Neurons in the Basolateral Amygdala by Anna Beyeler, Chia-Jung Chang, Margaux Silvestre, Clémentine Lévêque, Praneeth Namburi, Craig P. Wildes, Kay M. Tye. Cell Reports.
They show that basolateral amygdala (BLA) neurons projecting to nucleus accumbens (NAc), central amygdala (CeA) and ventral hippocampus (vHPC) are intermingled in distinct gradients. “Positive and negative valence-encoding BLA neurons are intermingled throughout BLA. Projection-defined BLA populations differ in the size of local networks recruited. BLA-CeA neurons suppress a larger local network than BLA-NAc or BLA-vHPC neurons”
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12. Medial preoptic circuit induces hunting-like actions to target objects and prey by Sae-Geun Park, Yong-Cheol Jeong, Dae-Gun Kim, Min-Hyung Lee, Anna Shin, Geunhong Park, Jia Ryoo, Jiso Hong, Seohui Bae, Cheol-Hu Kim, Phill-Seung Lee & Daesoo Kim. Nature Neuroscience.
They reveal a previously unknown function of the medial preoptic area (MPA) by showing that CaMKIIα+ MPA neurons are activated during object exploration and induce hunting-like actions toward 3D objects or natural prey. This suggests there is a continuum between object play and hunting behavior and explains how the brain organizes behavior during foraging.
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13. Insular cortex mediates approach and avoidance responses to social affective stimuli by Morgan M. Rogers-Carter, Juan A. Varela, Katherine B. Gribbons, Anne F. Pierce, Morgan T. McGoey, Maureen Ritchey & John P. Christianson. Nature Neuroscience.
“Searching for clues to complex social behaviors, experiments found that laboratory rats - much like humans - will approach distressed juveniles but avoid distressed adults -- responses known as social affective behaviors, researchers report. Additionally, the brain's insular cortex region is required for proper reactions to others in distress. Further, changes in insular cortex excitability, caused by the hormone oxytocin, likely account for the social affective behaviors.”
14. Reward-Predictive Neural Activities in Striatal Striosome Compartments by Tomohiko Yoshizawa, Makoto Ito and Kenji Doya. eNeuro.
Striosomes are striatal compartments that directly project to midbrain dopaminergic neurons. By using Inscopix nVista imaging and a striosome-Cre mouse line, they recorded striosomal neurons during a classical conditioning task and discovered reward-predictive activities proportional to the expected reward amount. Most reward-predictive activities of striosomal neurons were observed only in early or late stage of learning. “In addition, some striosomal neurons were directly activated by reward experiences. These results suggest that striosomal neurons transmit both expected and acquired reward signals to dopaminergic neurons.”
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