February brought a number of blockbuster papers related to neural circuit research, including two papers that applied Inscopix technology. The behaviors studied ranged from motor learning, sleep, decision-making, fear, thirst, hunting, predation, and evasion. Plus there’s a novel genetically encoded fluorescent voltage reporter this month! Two of the papers have videos that accompany them, so be sure to check them out.
1. Fast-Spiking Interneurons Supply Feedforward Control of Bursting, Calcium, and Plasticity for Efficient Learning by Scott F. Owen, Joshua D. Berke, Anatol C. Kreitzer. Cell.
Fast-spiking interneurons (FSIs) control gain and network plasticity, but little was known about how these two roles interact. Here they elucidated this link in the striatum by optogenetically inhibiting FSIs while recording calcium transients in neighboring medium spiny neurons (MSNs) using Inscopix’s nVoke. They expected FSI inhibition would disrupt motor control in mice, but instead found a surprising deficit in motor learning. FSIs regulated bursting, calcium ion influx, AMPA/NMDA ratios and synaptic plasticity in MSNs.
2. A Hypothalamic Switch for REM and Non-REM Sleep by Kai-Siang Chen, Min Xu, Zhe Zhang, Wei-Cheng Chang, Thomas Gaj, David V. Schaffer, Yang Dan. Neuron.
They used calcium imaging with the Inscopix nVista system to link dorsomedial hypothalamus (DMH) neuron activity with different brain states during sleep. They found two subtypes of inhibitory neurons. One inhibitory neuron is most active during REM sleep, and the other has the lowest activity during REM sleep. They used optogenetics to activate each group of DMH neurons and found that preoptic-area-projecting neurons have the lowest activity during REM sleep and activating them switched REM sleep to non-REM sleep, while the brainstem-projecting neurons showed the opposite effect.
3. Hippocampus-driven feed-forward inhibition of the prefrontal cortex mediates relapse of extinguished fear by Roger Marek, Jingji Jin, Travis D. Goode, Thomas F. Giustino, Qian Wang, Gillian M. Acca, Roopashri Holehonnur, Jonathan E. Ploski, Paul J. Fitzgerald, Timothy Lynagh, Joseph W. Lynch, Stephen Maren & Pankaj Sah. Nature Neuroscience.
They study the role of medial prefrontal cortex (mPFC) in the extinction of conditioned fear memories, and found that ventral hippocampal (vHPC) projections to the infralimbic (IL) cortex recruited parvalbumin-expressing interneurons to counter extinction and promote fear relapse.
4. Roles of prefrontal cortex and mediodorsal thalamus in task engagement and behavioral flexibility by Tobias Marton, Helia Seifikar, Francisco J. Luongo, Anthony T. Lee and Vikaas S. Sohal. Journal of Neuroscience.
The prefrontal cortex is involved in just about everything, but especially in decision-making. Here mice perform tasks where they make choices based on sensory cues, like a sound. When mice hear the sound and perform the choice-selection task based on the auditory cue, neural responses are suppressed in the auditory cortex. They show that the suppression results from “top-down” regulation from the prefrontal cortex. This phenomena isn’t critical for task performance, but if you selectively disrupt mPFC outputs to the mediodorsal thalamus, this prevents switching between auditory and visual rules, suggesting the prefrontal cortex comprises multiple dissociable circuits related to behavioral flexibility and sensory processing.
Read more here
5. A robotic multidimensional directed evolution approach applied to fluorescent voltage reporters by Kiryl D. Piatkevich, Erica E. Jung, Christoph Straub, Changyang Linghu, Demian Park, Ho-Jun Suk, Daniel R. Hochbaum, Daniel Goodwin, Eftychios Pnevmatikakis, Nikita Pak, Takashi Kawashima, Chao-Tsung Yang, Jeffrey L. Rhoades, Or Shemesh, Shoh Asano, Young-Gyu Yoon, Limor Freifeld, Jessica L. Saulnier, Clemens Riegler, Florian Engert, Thom Hughes, Mikhail Drobizhev, Balint Szabo, Misha B. Ahrens, Steven W. Flavell, Bernardo L. Sabatini & Edward S. Boyden. Nature Chemical Biology.
Using robotics, they optimize on a novel genetically encoded fluorescent voltage indicator, and show its successful use in a number of systems, including imaging spiking and millivolt-scale subthreshold and synaptic activity in acute mouse brain slices and in larval zebrafish in vivo. This paper has huge implications for the tools available to study neural circuits, needless to say.
6. Hypothalamic Circuits for Predation and Evasion by Yi Li, Jiawei Zeng, Juen Zhang, Chenyu Yue, Weixin Zhong, Zhixiang Liu, Qiru Feng, Minmin Luo. Neuron.
The seemingly opposite behaviors of predation and evasion are tightly regulated by two dissociable modular command systems within a single neural projection from the lateral hypothalamus to the periaqueductal gray.
7. Prefrontal-Periaqueductal Gray-Projecting Neurons Mediate Context Fear Discrimination by Robert R. Rozeske, Daniel Jercog, Nikolaos Karalis, Fabrice Chaudun, Suzana Khoder, Delphine Girard, Nânci Winke, Cyril Herry. Neuron.
Using single-unit recording and optogenetic manipulations in a fear-conditioning paradigm, they demonstrate that activation of a subpopulation of cells in the prefrontal cortex projecting to the periaqueductal gray is necessary and sufficient for context fear discrimination.
Read more here
8. Hierarchical neural architecture underlying thirst regulation by Vineet Augustine, Sertan Kutal Gokce, Sangjun Lee, Bo Wang, Thomas J. Davidson, Frank Reimann, Fiona Gribble, Karl Deisseroth, Carlos Lois & Yuki Oka. Nature.
They reveal specific dynamic thirst circuits between the subfornical organ and the median preoptic nucleus that integrate the homeostatic-instinctive requirement for fluids and the consequent drinking behavior to maintain internal water balance.
9. Teneurin-3 controls topographic circuit assembly in the hippocampus by Dominic S. Berns, Laura A. DeNardo, Daniel T. Pederick & Liqun Luo. Nature.
Teneurins, transmembrane proteins, have previously been shown to be required for the development of the vertebrate visual system development. Here they show that mouse teneurin-3 is expressed in multiple topographically interconnected areas of the hippocampal region, and provide intriguing evidence that teneurin-3 may orchestrate the assembly of a complex distributed circuit in the mammalian brain via matching expression and homophilic attraction.
Read more here
10. 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 use a head-mounted photostimulation device to show that neurons positive for the α subunit of Ca2+/calmodulin-dependent kinase II in the medial preoptic area (MPA) that send projections to the ventral periaqueductal gray (vPAG) mediate target-directed actions in mice.