Must-Read Neural Circuit Papers in August 2018
There were so many interesting neuroscience papers published in August relevant to neural circuits that curation across journals was extra challenging. Here you go!
1. Calcium Transient Dynamics of Neural Ensembles in the Primary Motor Cortex of Naturally Behaving Monkeys by Takahiro Kondo, Risa Saito, Masaki Otaka, Kimika Yoshino-Saito, Akihiro Yamanaka, Tetsuo Yamamori, Akiya Watakabe, Hiroaki Mizukami, Mark J. Schnitzer, Kenji F. Tanaka, Junichi Ushiba, Hideyuki Okano. Cell Reports.
This is a first! They applied nVista technology to image calcium transients in neurons of the motor cortex of marmosets as they freely behaved. This novel application opens up the possibility to dissect large-scale neural circuits during human-relevant behavior under natural conditions. The combination of Inscopix brain imaging systems with transgenic marmoset technologies has the potential to transform our understanding, diagnosis, and treatment of human brain diseases.
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2. In vivo measurement of afferent activity with axon-specific calcium imaging by Gerard Joey Broussard, Yajie Liang, Marina Fridman, Elizabeth K. Unger, Guanghan Meng, Xian Xiao, Na Ji, Leopoldo Petreanu & Lin Tian. Nature Neuroscience.
They created an axon-targeted genetically encoded calcium indicator, axon-GCaMP6, which enriches exclusively in local or distal axon. Importantly, Axon-GCaMP6 is photostable and displays enhanced signal to noise ratio, making it a significant improvement over prior targeted GECIs. Axon-GCaMPs enable new applications of calcium imaging with subcellular resolution noninvasively in deep cortical layers.
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3. Anatomically Defined and Functionally Distinct Dorsal Raphe Serotonin Sub-systems by Jing Ren, Drew Friedmann, Jing Xiong, Cindy D. Liu, Brielle R. Ferguson, Tanya Weerakkody, Katherine E. DeLoach, Chen Ran, Albert Pun, Yanwen Sun, Brandon Weissbourd, Rachael L. Neve, John Huguenard, Mark A. Horowitz, Liqun Luo. Cell.
In the mammalian brain, the dorsal raphe contains the largest single concentration of neurons that release serotonin to affect thinking, memory, and the regulation of moods and bodily functions. By injecting viruses that infect serotonin axons in regions which receive inputs from the dorsal raphe, the authors traced the connections back to their origin neurons in the dorsal raphe. This allowed them to create a visual map of projections between the dense concentration of serotonin-releasing neurons in the brainstem to the various regions of the forebrain that they influence. The map revealed two distinct groups of serotonin-releasing neurons in the dorsal raphe, which connected to cortical and subcortical regions in the brain.
4. Molecular Diversity and Specializations among the Cells of the Adult Mouse Brain by Arpiar Saunders, Evan Z. Macosko, Alec Wysoker, Melissa Goldman, Fenna M. Krienen, Heather de Rivera, Elizabeth Bien, Matthew Baum, Laura Bortolin, Shuyu Wang, Aleksandrina Goeva, James Nemesh, Nolan Kamitaki, Sara Brumbaugh, David Kulp, Steven A. McCarroll. Cell.
They generated a cellular atlas of the mouse brain, based on the gene expression profiles of nearly 700,000 individual cells covering nine major brain regions including frontal and posterior cortex, hippocampus, cerebellum, thalamus, striatum, and substantia nigra. They produced an unbiased characterization of the brain's diversity, providing a valuable dataset for linking cell types to circuits.
5. Coordinated Reductions in Excitatory Input to the Nucleus Accumbens Underlie Food Consumption by Sean J. Reed, Christopher K. Lafferty, Jesse A. Mendoza, Angela K. Yang, Thomas J. Davidson, Logan Grosenick, Karl Deisseroth, Jonathan P. Britt. Neuron.
They compared the activity profiles of amygdala, hippocampal, and thalamic inputs to the nucleus accumbens shell in mice performing a cued reward-seeking task using GCaMP-based fiber photometry. They found that the rostral and caudal ends of the NAc shell are innervated by distinct but intermingled populations of forebrain neurons that exhibit divergent feeding-related activity.
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6. Mouse Motor Cortex Coordinates the Behavioral Response to Unpredicted Sensory Feedback by Matthias Heindorf, Silvia Arber, Georg B. Keller. Neuron.
To investigate the role of motor cortex (M1) in sensory guided motor coordination, they trained mice to navigate a virtual corridor and found that M1 is essential for execution and learning of this visually guided task. Turn-selective layer 2/3 and layer 5 pyramidal tract (PT) neuron activation was shaped differentially with learning but scaled linearly with turn acceleration during spontaneous turns. During induced turns, however, layer 2/3 neurons were activated independent of behavioral response, while PT neurons still encoded behavioral response magnitude. Thus, the motor cortex is necessary for the execution of corrective movements in response to unexpected changes of sensory input but not when the same movements are executed spontaneously.
7. Transcriptomic and morphophysiological evidence for a specialized human cortical GABAergic cell type by Eszter Boldog, Trygve E. Bakken, Rebecca D. Hodge, Mark Novotny, Brian D. Aevermann, Judith Baka, Sándor Bordé, Jennie L. Close, Francisco Diez-Fuertes, Song-Lin Ding, Nóra Faragó, Ágnes K. Kocsis, Balázs Kovács, Zoe Maltzer, Jamison M. McCorrison, Jeremy A. Miller, Gábor Molnár, Gáspár Oláh, Attila Ozsvár, Márton Rózsa, Soraya I. Shehata, Kimberly A. Smith, Susan M. Sunkin, Danny N. Tran, Pratap Venepally, Abby Wall, László G. Puskás, Pál Barzó, Frank J. Steemers, Nicholas J. Schork, Richard H. Scheuermann, Roger S. Lasken, Ed S. Lein & Gábor Tamás. Nature Neuroscience.
This made a big splash in the news, so you probably already know all about “rosehip” neurons. Rosehip cells show an immunohistochemical profile (GAD1+CCK+, CNR1–SST–CALB2–PVALB–) matching a single transcriptomically defined cell type whose specific molecular marker signature is not seen in mouse cortex. Rosehip cells in layer 1 make homotypic gap junctions, predominantly target apical dendritic shafts of layer 3 pyramidal neurons, and inhibit backpropagating pyramidal action potentials in microdomains of the dendritic tuft. These cells are therefore positioned for potent local control of distal dendritic computation in cortical pyramidal neurons. NIMH Director Joshua Gordon, who was not involved in the study, says this discovery in the human brain is likely to be the tip of the iceberg!
8. Transforming Sensory Cues into Aversive Emotion via Septal-Habenular Pathway by Guang-Wei Zhang, Li Shen, Wen Zhong, Ying Xiong, Li I. Zhang, Huizhong W. Tao. Neuron.
Zhang et al. reveal a neural circuit for processing innately aversive sensory signals, with glutamatergic projections from medial septum (MS) to lateral habenula (LHb) and preoptic area (POA) to generate the negative emotional effect. This role of MS in mediating aversion is previously unrecognized.
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9. Inhibitory Control of Prefrontal Cortex by the Claustrum by Jesse Jackson, Mahesh M. Karnani, Boris V. Zemelman, Denis Burdakov, Albert K. Lee. Neuron.
The claustrum provides a dense synaptic input to the cortex, but how claustrocortical projections modulate cortical activity is not known. Here they show that claustrocortical connections serve to inhibit cortical neural networks by activating specific subtypes of cortical interneurons (Prefrontal NPY and PV).
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10. Integrating time from experience in the lateral entorhinal cortex by Albert Tsao, Jørgen Sugar, Li Lu, Cheng Wang, James J. Knierim, May-Britt Moser & Edvard I. Moser. Nature.
They identified a network of cells in the entorhinal cortex that appear to play a key role into putting experience into a temporal context.
11. 5-HT release in nucleus accumbens rescues social deficits in mouse autism model by Jessica J. Walsh, Daniel J. Christoffel, Boris D. Heifets, Gabriel A. Ben-Dor, Aslihan Selimbeyoglu, Lin W. Hung, Karl Deisseroth & Robert C. Malenka. Nature.
They “demonstrate that stimulating 5-HT release in the NAc promotes sociability, effects that require activation of NAc 5-HT1b receptors. Inhibition of DR 5-HT neurons or their terminals in the NAc reduced social interactions, suggesting that 5-HT action in the NAc is necessary for normal levels of sociability. Consistent with this conclusion, increases in DR 5-HT neuron activity occur during non-aggressive social interactions, including mating, although increases may also occur during sucrose or food intake. Stimulating 5-HT release in the NAc did not elicit acute reinforcement or changes in a variety of control behaviours. These behavioural effects of 5-HT in the NAc are markedly different from the acute reinforcing properties of the release of dopamine in the NAc, suggesting critical differences in the NAc circuitry modulation by which these major neuromodulators mediate their behavioural effects.”
12. Regulation of striatal cells and goal-directed behavior by cerebellar outputs by Le Xiao, Caroline Bornmann, Laetitia Hatstatt-Burklé & Peter Scheiffele. Nature Communications.
They performed an in-depth mapping of cerebello-striatal connections in mice, and uncovered dense connectivity from the interposed deep cerebellar nucleus via the parafascicular and centrolateral nuclei to the dorsal striatum. They find that DCN outputs are relayed to MSNs but also striatal ChAT interneurons. Silencing of DCN outputs modifies the function of striatal ChAT interneurons and impairs behavioral performance of mice in a striatum-dependent task. Their findings suggest that cerebello-striatal connections from interposed DCN relay cerebellar computations to several striatal cell types.
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13. Anterolateral motor cortex connects with a medial subdivision of ventromedial thalamus through cell-type-specific circuits, forming an excitatory thalamo-cortico-thalamic loop via layer 1 apical tuft dendrites of layer 5B pyramidal tract type neurons by KuangHua Guo, Naoki Yamawaki, Karel Svoboda and Gordon M. G. Shepherd. Journal of Neuroscience.
“Anterolateral motor cortex (ALM), a higher-order motor area in the mouse, and ventromedial thalamus (VM) are anatomically and functionally linked, but their synaptic interconnections at the cellular level are unknown. Our results show that ALM pyramidal tract neurons monosynaptically excite ALM-projecting thalamocortical neurons in a medial subdivision of VM, and vice versa. The thalamo-cortico-thalamic loop formed by these recurrent connections constitutes a circuit-level substrate for supporting reverberant activity in this system.”
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14. The memory for time and space differentially engages the proximal and distal parts of the hippocampal subfields CA1 and CA3 by Zachery Beer, Peter Vavra, Erika Atucha, Katja Rentzing, Hans-Jochen Heinze, Magdalena M. Sauvage. PLOS Biology.
This is an intriguing result. “Departing from the most influential model of episodic memory (the two-streams hypothesis), we have recently proposed a new concept of information processing in the hippocampus according to which “what” one remembers and “where” or “when” it happens might be processed by distinct subnetworks segregated along the proximodistal axis of the hippocampus, a brain region tied to memory function, instead of being systematically integrated at this level. Here, we focused on the processing of temporal and/or spatial information in the proximal and distal parts of CA1 and CA3 in mice to test whether the two concepts are reconcilable. To do so, we used an imaging method with cellular resolution based on the detection of the RNA of the Immediate Early Gene (IEG) Arc, which is tied to synaptic plasticity and memory demands, and correlated imaging results with memory performance. Our data confirm the existence of subnetworks segregated along the proximodistal axis of CA1 and CA3 that preferentially process spatial and non-spatial information and suggest a key involvement of distal CA1 in temporal information processing. In addition, they show that the two models are complementary to a large extent and posit the “segregated” model as a viable alternative for the two-streams hypothesis.”
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