For August, we selected 10 papers that cover the circuit mechanisms involved in a full spectrum of behaviors, including feeding, moving, sleeping, socializing, remembering, and scratching an itch. Most of the studies listed below record and manipulate activity in specific neuronal populations in freely moving mice. Three of the studies apply the Inscopix nVista system for mapping neural circuits in real time during active behavior, and are excellent examples of functional cell-type mapping and neural coding.
1. Modulation of prefrontal cortex excitation/inhibition balance rescues social behavior in CNTNAP2-deficient mice by Aslihan Selimbeyoglu, Christina K. Kim, Masatoshi Inoue, Soo Yeun Lee, Alice S. O. Hong, Isaac Kauvar, Charu Ramakrishnan, Lief E. Fenno, Thomas J. Davidson, Matthew Wright, Karl Deisseroth. Science Translational Medicine.
This is an important paper for getting at the mechanisms of autism, and paves the way for greater investigation into circuits and molecules involved. They use optogenetics to modulate the excitation/inhibition balance in the prefrontal cortex of an autism-like mouse model and saw rescue of social behavior deficits.
2. Distinct Neural Circuits for the Formation and Retrieval of Episodic Memories by Dheeraj S. Roy, Takashi Kitamura, Teruhiro Okuyama, Sachie K. Ogawa, Chen Sun, Yuichi Obata, Atsushi Yoshiki, Susumu Tonegawa. Cell.
A beautiful study demonstrating a detour circuit involving the subiculum as necessary for memory recall but not for memory formation. However, the direct circuit from CA1 to the entorhinal cortex is not necessary for memory recall, but is required for memory formation. This is a great example of mapping cell types to function.
3. Central amygdala circuits modulate food consumption through a positive-valence mechanism by Amelia M Douglass, Hakan Kucukdereli, Marion Ponserre, Milica Markovic, Jan Gründemann, Cornelia Strobel, Pilar L Alcala Morales, Karl-Klaus Conzelmann, Andreas Lüthi & Rüdiger Klein. Nature Neuroscience.
They show that central amygdala Htr2a neurons increase in activity specifically during food consumption. They found evidence that Htr2a neurons encode the value of food. By activating the HTR2a cells, the researchers were able to condition mice to prefer a specific taste that was initially less preferred.
4. Selective inhibitory control of pyramidal neuron ensembles and cortical subnetworks by chandelier cells by Jiangteng Lu, Jason Tucciarone, Nancy Padilla-Coreano, Miao He, Joshua A Gordon & Z Josh Huang. Nature Neuroscience.
How do inhibitory neurons regulate processing streams of pyramidal cells in the cortex? Here, they showed that a subset of GABAergic chandelier cells in the prelimbic cortex selectively control pyramidal cells projecting to the basolateral amygdala. Accordingly, optogenetic activation of chandelier cells rapidly suppresses basolateral pyramidal cell activity in freely behaving mice.
5. A central neural circuit for itch sensation by Di Mu, Juan Deng, Ke-Fei Liu, Zhen-Yu Wu, Yu-Feng Shi, Wei-Min Guo, Qun-Quan Mao, Xing-Jun Liu, Hui Li, Yan-Gang Sun. Science.
This paper received a lot of social media attention. They ask how itch information is transmitted to the brain and what central circuits underlie itch-induced scratching behavior. They reveal a central neural circuit involving the the spinoparabrachial pathway that is critical for itch signal processing.
6. Molecular and Circuit-Dynamical Identification of Top-Down Neural Mechanisms for Restraint of Reward Seeking by Christina K. Kim, Li Ye, Joshua H. Jennings, Nandini Pichamoorthy, Daniel D. Tang, Ai-Chi W. Yoo, Charu Ramakrishnan, Karl Deisseroth. Cell.
How do we stop ourselves from seeking rewards in the face of a punishment, such as in addiction? Here they find that taking action with known risk of punishment involves acutely diminished medial prefrontal cortex to nucleus accumbens (but not mPFC→VTA) influence. Activity within specific substreams of the mPFC→NAc projection both signals information about prior aversive outcomes and serves to suppress the taking of the rewarding action.
Read more here.
7. Input-Timing-Dependent Plasticity in the Hippocampal CA2 Region and Its Potential Role in Social Memory by Felix Leroy, David H. Brann, Torcato Meira, Steven A. Siegelbaum. Neuron.
“Input-timing-dependent plasticity (ITDP) is a circuit-based synaptic learning rule by which paired activation of entorhinal cortical (EC) and Schaffer collateral (SC) inputs to hippocampal CA1 pyramidal neurons (PNs) produces a long-term enhancement of SC excitation.” Here they find that pairing EC and SC inputs also induces ITDP of SC excitation of CA2 projection neurons. However, they note a distinct cellular and molecular mechanism from CA1 ITDP. The also find that CA2 ITDP is associated with enhanced social memory.
Read more here.
8. Lhx6-positive GABA-releasing neurons of the zona incerta promote sleep by Kai Liu, Juhyun Kim, Dong Won Kim, Yi Stephanie Zhang, Hechen Bao, Myrto Denaxa, Szu-Aun Lim, Eileen Kim, Chang Liu, Ian R. Wickersham, Vassilis Pachinis, Samer Hattar, Juan Song, Solange P. Brown & Seth Blackshaw. Nature.
GABAergic Lhx6+ ventral zona incerta (VZI) neurons promote both NREM and REM sleep, rather than either alone. They also exhibit a relatively slow-onset but long-lasting regulation of sleep. “Lhx6+ VZI neurons receive inputs from multiple different subtypes of sleep-regulating neurons, and are directly presynaptic to wake-promoting GABAergic and Hcrt+ neurons of the lateral hypothalamus and inhibit their activity, with this latter function being essential for their promotion of NREM sleep.”
9. The Spatiotemporal Organization of the Striatum Encodes Action Space by Andreas Klaus, Gabriela J. Martins, Vitor B. Paixao, Pengcheng Zhou, Liam Paninski, and Rui M. Costa. Neuron.
How does the brain generate behavior? They measured the spatiotemporal neuronal dynamics (by using Inscopix nVista) of the two major striatal projection pathways (SPN) in the dorsal striatum during self-paced, natural movements. They demonstrate action-specific SPNs are more correlated and spatially closer to each other and encodes action space beyond movement speed.
10. Role of somatostatin-positive cortical interneurons in the generation of sleep slow waves by Chadd M. Funk, Kayla Peelman, Michele Bellesi, William Marshall, Chiara Cirelli and Giulio Tononi. Journal of Neuroscience.
Somatostatin-positive cells, but not parvalbumin-positive cells, are involved in the generation of sleep slow waves, the form of NREM sleep thought to be the most restorative. This is the first evidence that links a specific class of inhibitory interneuron to the generation of slow waves during NREM sleep in freely moving mice.
Read more here.