The summer is nearing the end (unbelievably!), and we have a new list of neural circuit papers published in July. What is the criteria for the papers that make this list? I’m looking for studies that either open the way (or provide a novel resource/method) for a deeper dive into circuit mechanisms and/or ideally work out something conceptually interesting about the function and/or organization of a neural circuit (be it micro, meso or macro) in the context of ethologically relevant behaviors. I endeavor to search across all journals that publish neuroscience, and try to be journal and author agnostic. I draw on my background in systems neuroscience research and the almost 6 years I spent as a scientific editor at PLOS Biology.
1. Activity-Dependent Gating of Parvalbumin Interneuron Function by the Perineuronal Net Protein Brevican by Emilia Favuzzi, André Marques-Smith, Rubén Deogracias, Christian M. Winterflood, Alberto Sánchez-Aguilera, Laura Mantoan, Patricia Maeso, Cathy Fernandes, Helge Ewers, Beatriz Rico. Neuron.
This study bridges molecular, cellular and potential circuit mechanisms for learning and memory via Parvalbumin Interneurons. They point to a behavioral and circuit paradigm that can be further studied in the hippocampus.
2. A circuit-based mechanism underlying familiarity signaling and the preference for novelty by Susanna Molas, Rubing Zhao-Shea, Liwang Liu, Steven R DeGroot, Paul D Gardner & Andrew R Tapper. Nature Neuroscience.
What happens in the brain when novel stimuli becomes familiar? Molas et al. demonstrate that familiarity activates the interpeduncular nucleus, thereby reducing motivation to explore. Familiarity signaling in the interpeduncular nucleus is modulated by habenula and ventral tegmental area afferents to control novelty preference. This paper indicates that information regarding familiar and novel stimuli is signaled through independent yet connected circuits.
Read more here
3. Network-Level Control of Frequency Tuning in Auditory Cortex by Hiroyuki K. Kato, Samuel K. Asinof, Jeffry S. Isaacson. Neuron.
They find that lateral inhibition in auditory cortex is mediated by both the convergence of inputs onto somatostatin cells and divergence of outputs from somatostatin cells. They suggest that somatostatin cells work as a “hub for the lateral flow of information in cortical circuits, and regulate the integration of information across spatially distributed auditory frequency domains.” They link a cortical cell type to a function in frequency tuning.
Read more here
4. An optogenetic toolbox for unbiased discovery of functionally connected cells in neural circuits by Dominique Förster, Marco Dal Maschio, Eva Laurell & Herwig Baier. Nature Communications.
The researchers expressed the light-sensitive ChrimsonR ion channel and GCAMP6 into individual neurons in the brain of zebrafish larvae. They were able to look at local and long-range connections in a behaving zebrafish. “With Optobow we were able to show for the first time which neurons are connected with each other in the brain of a living, active animal, for example when a behavioral command is generated in the brain.” said Herwig Baier. This method allows the identification of the cellular components of neuronal circuits and connectivity in the context of behavior.
5. Basolateral amygdala to orbitofrontal cortex projections enable cue-triggered reward expectations by Nina T. Lichtenberg, Zachary T. Pennington, Sandra M. Holley, Venuz Y. Greenfield, Carlos Cepeda, Michael S. Levine and Kate M. Wassum. Journal of Neuroscience
The more accurately we can predict reward, the better the outcomes. This study shows that BLA→OFC projections impart information about environmental stimuli thereby facilitating adaptive behavior which can generate expectations of potential future rewarding events.
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6. Identification of a Brainstem Circuit Controlling Feeding by Alexander R. Nectow, Marc Schneeberger, Hongxing Zhang, Bianca C. Field, Nicolas Renier, Estefania Azevedo, Bindiben Patel, Yupu Liang, Siddhartha Mitra, Marc Tessier-Lavigne, Ming-Hu Han, Jeffrey M. Friedman. Cell.
This beautiful work establishes the dorsal raphe nucleus as a node controlling energy balance through its effect on the regulation of feeding behavior.
7. Social Control of Hypothalamus-Mediated Male Aggression byTaehong Yang, Cindy F. Yang, M. Delara Chizari, Niru Maheswaranathan, Kenneth J. Burke Jr., Maxim Borius, Sayaka Inoue, Michael C. Chiang, Kevin J. Bender, Surya Ganguli, Nirao M. Shah. Neuron.
Understanding the behavioral relevance of a network of neurons is tricky business. Here, they identified a genetically defined neural population in the hypothalamus that is necessary and sufficient for aggression in solitary male mice, but not in socially raised males (unless their pheromone-sensing is blocked). In other words, this neural system in the ventromedial hypothalamus can take social context into account when regulating aggression.
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8. Initiation of Behavioral Response to Antidepressants by Cholecystokinin Neurons of the Dentate Gyrus by Lucian Medrihan, Yotam Sagi, Zintis Inde, Oleh Krupa, Chelsea Daniels, Adrien Peyrache, Paul Greengard. Neuron.
How do selective serotonin reuptake inhibitors (SSRIs) work at the cellular and molecular level? Here they show that SSRIs act on cholecystokinin (CCK) inhibitory interneurons of the mouse dentate gyrus (DG) via serotonin 5-HT1B receptors. Their activation inhibits GABA release, which in turn disinhibits parvalbumin (PV) interneurons and, as a consequence, reduces the neuronal activity of the granule cells. “Finally, inhibition of CCK neurons mimics the antidepressant behavioral effects of SSRIs, suggesting that these cells may represent a novel cellular target for the development of fast-acting antidepressant drugs.” Thus, they conclude that CCK neurons in the DG are essential for the initial SSRI response, and involve functional changes in the DG microcircuit associated with this response.
9. Activation of cortical somatostatin interneurons prevents the development of neuropathic pain by Joseph Cichon, Thomas J J Blanck, Wen-Biao Gan & Guang Yang. Nature Neuroscience.
They identify specific cortical interneurons as therapeutic targets for neuropathic pain. These findings reveal cortical circuit changes that arise during neuropathic pain and identify the activation of specific cortical interneurons as therapeutic targets for chronic pain treatment.
10. Synaptic organization of visual space in primary visual cortexby M. Florencia Iacaruso, Ioana T. Gasler & Sonja B. Hofer. Nature.
The authors intricately mapped functional inputs onto individual L2/3 pyramidal cells in mouse visual cortex. They confirm inputs representing similar visual features from overlapping locations in visual space were more likely to cluster on nearby spines. But when they looked at inputs from visual field regions beyond the receptive field of the postsynaptic neuron, they saw synapses on higher-order dendritic branches. These long-range inputs are more likely to share the preference for oriented edges with the postsynaptic neuron when “the receptive field of the input is spatially displaced along the axis of the receptive field orientation of the postsynaptic neuron.” As the authors say, this organization of synaptic connectivity is ideally suited for the amplification of elongated edges, which are enriched in the visual environment, and thus provides a potential neural circuit substrate for contour integration and object grouping.
11. Columnar Segregation of Magnocellular and Parvocellular Streams in Human Extrastriate Cortex by Roger B.H. Tootell and Shahin Nasr. Journal of Neuroscience.
Yes, like non-human primates, humans also have segregated parallel processing channels throughout much of human visual cortices. The authors tested known functional distinctions in M-P streams like color vs. luminance, peak spatial frequency, etc. It’s important to know that what we find in neural circuitry for vision in NHPs holds true for functional connections in humans.
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12. A multiscale cerebral neurochemical connectome of the rat brain Hamid R. Noori, Judith Schöttler, Maria Ercsey-Ravasz, Alejandro Cosa-Linan, Melinda Varga, Zoltan Toroczkai, Rainer Spanagel. PLOS Biology.
They utilize advanced supervised machine learning and integrate over 50 years of neuroanatomy research on rat brains into a consistent multiscale, multilayer neurochemical cerebral connectome. This resource could potentially expand our understanding of neuroconnectomics beyond binary constructs and serve as an important resource for future work. I also like studies that span scales, and this one makes excellent use of existing datasets.
Read more here.
13. Genetic identification of a hindbrain nucleus essential for innate vocalization by Luis Rodrigo Hernandez-Miranda, Pierre-Louis Ruffault, Julien C. Bouvier, Andrew J. Murray, Marie-Pierre Morin-Surun, Niccolò Zampieri, Justyna B. Cholewa-Waclaw, Elodie Ey, Jean-Francois Brunet, Jean Champagnat, Gilles Fortin, and Carmen Birchmeier. PNAS
They show that the hindbrain nucleus tractus solitarius (NTS) is essential for vocalization in mice. During vocalization, the NTS coordinates sensory inputs and motor outputs via functional connection with L1 and nucleus ambiguus motor pools where expiratory and laryngeal motor neurons reside. When the development of Phox2b+ NTS neurons is disrupted, mice pups can breathe, but are mute and receive less care from their mothers. This study paves the way for a more in-depth neural circuit analysis with cell types during vocalization.