Must-Read Neural Circuit Papers in April 2018

nVista technology to study time cells

For neural circuit papers published in April, we highlight two that uncover the neural basis of parental behavior. Another paper uses nVista technology to study time cells. Other papers detail a circuit relevant to metabolic disease, another to aggression, and another implicates prelimbic cortex in fear extinction. Also don’t miss papers that study connections between thalamus and prefrontal cortex, cortical feedback in primary visual cortex, or subiculum neurons in spatial recognition. Happy reading!

1. The Same Hippocampal CA1 Population Simultaneously Codes Temporal Information over Multiple Timescales by William Mau, David W. Sullivan, Nathaniel R. Kinsky, Michael E. Hasselmo, Marc W. Howard, Howard Eichenbaum. Current Biology.

In a fitting tribute to Howard Eichenbaum, Mau et al. used Inscopix nVista calcium imaging to record from CA1 neurons of mice running in place during a simple goal-seeking task. They saw time cell sequences and found there was sufficient temporal information contained in the temporal structure for a Bayesian classifier to faithfully decode elapsed time. This information was preserved over multiple days. They also measured the time cell ensemble as it systematically varied with the passage of minutes and days. This time-dependent variance also contained temporal information, in parallel with and on larger scales compared to the content of time cell sequences. The authors conclude that the hippocampus has the capacity to encode temporal information along multiple timescales in support of episodic memory.

Read more here.

2. Functional circuit architecture underlying parental behaviour by Johannes Kohl, Benedicte M. Babayan, Nimrod D. Rubinstein, Anita E. Autry, Brenda Marin-Rodriguez, Vikrant Kapoor, Kazunari Miyamishi, Larry S. Zweifel, Liqun Luo, Naoshige Uchida & Catherine Dulac. Nature.

Having previously identified galanin-producing parental neurons, here they determined using viral neuronal tracing, optogenetics and photometry, which brain regions these parenting neurons were communicating with, and the consequences on parental behavior.

Read more here and here.

3. Reciprocal Circuits Linking the Prefrontal Cortex with Dorsal and Ventral Thalamic Nuclei by David P. Collins, Paul G. Anastasiades, Joseph J. Marlin, Adam G. Carter. Neuron.

They show that prefrontal cortex (PFC) engages multiple thalamic nuclei, and that dorsal and ventral thalamus in turn target distinct networks within the PFC. They complete a loop connecting thalamic input with cortico-thalamic output with local connectivity in the PFC. These results define the cellular and synaptic properties of reciprocal circuits between the PFC and thalamus.

Read more here

4. The functional organization of cortical feedback inputs to primary visual cortex by Tiago Marques, Julia Nguyen, Gabriela Fioreze & Leopoldo Petreanu. Nature Neuroscience.

The authors used Ca2+ imaging of feedback axons in the mouse visual cortex to measure the organization of cortical feedback inputs. They found that the locations in visual cortex targeted by feedback axons relate to their tuning properties according to a simple geometrical rule. Feedback inputs from Lateromedial visual area are functionally organized in V1, with their tuning properties determining the retinotopic locations they innervate.

Read more here.

5. Genetic identification of leptin neural circuits in energy and glucose homeostases by Jie Xu, Christopher L. Bartolome, Cho Shing Low, Xinchi Yi, Cheng-Hao Chien, Peng Wang & Dong Kong. Nature.

They used CRISPR–Cas9-mediated genetic ablation of leptin or its receptors in vivo to identify AgRP as the major neuronal target of leptin in the brain. They uncovered two distinct mechanisms through which leptin inhibits AgRP neurons: 1) presynaptic mechanism in which neurons secreting the neuroinhibitor GABA innervate AgRP neurons to mediate leptin’s acute effects on feeding, 2) a postsynaptic mechanism in which a potassium channel sensitive to the nucleotide ATP is required for leptin to act on AgRP neurons to regulate energy balance, food intake, and blood sugar. This study “identifies the fundamental component of the neural circuits governing energy and blood glucose regulation and will facilitate future studies seeking therapeutic interventions for obesity and diabetes.”

Read more here and here.

A hypothalamic circuit for the circadian control of aggression

6. A hypothalamic circuit for the circadian control of aggression by William D. Todd, Henning Fenselau, Joshua L. Wang, Rong Zhang, Natalia L. Machado, Anne Venner, Rebecca Y. Broadhurst, Satvinder Kaur, Timothy Lynagh, David P. Olson, Bradford B. Lowell, Patrick M. Fuller & Clifford B. Saper. Nature Neuroscience.

They demonstrate, for the first time, that aggression propensity in male mice exhibits a daily rhythm. They then show, using genetically targeted disruption and inhibition, that this rhythm in aggression propensity requires normal functioning of GABAergic subparaventricular zone (SPZ) neurons and is independent of locomotor activity and plasma corticosterone rhythms. Using the ChR2-assisted circuit mapping approach, they uncover a functional polysynaptic circuit connecting the suprachiasmatic nucleus (SCN) clock with ventrolateral part of the ventromedial nucleus of the hypothalamus (VMHvl) neurons known to regulate attack behavior. They also show a parallel pathway from the SPZ through PACAP+ (peptide pituitary adenylate cyclase activation polypeptide) neurons within the central VMH, highly interconnected with the VMHvl and forming an intra-VMH circuit that, upon activation, also drives attack behavior.

Read more here and here.

7. Excitatory connections between the prelimbic and infralimbic medial prefrontal cortex show a role for the prelimbic cortex in fear extinction by Roger Marek, Li Xu, Robert K. P. Sullivan & Pankaj Sah. Nature Neuroscience.

“Prelimbic (PL) and infralimbic (IL) mPFC are thought to mediate fear expression and fear extinction, respectively. The authors show that PL projects to IL and innervates projections to amygdala and that this connection is engaged in fear extinction.”

Read more here.

8. Dissociable Structural and Functional Hippocampal Outputs via Distinct Subiculum Cell Classes by

Mark S. Cembrowski, Matthew G. Phillips, Salvatore F. DiLisio, Brenda C. Shields, Johan Winnubst, Jayaram Chandrashekar, Erhan Bas, Nelson Spruston. Cell.

“They investigated pyramidal cells in the dorsal region of the subiculum – an area linked to the processing of information about the animal’s environment – using a multi-pronged approach, integrating methods from cell biology, genetics, circuit analysis, and behavioral neuroscience to zero in on the neural roots of spatial recognition.”

Read more here and here.

9. A Hypothalamic Midbrain Pathway Essential for Driving Maternal Behaviors by Yi-Ya Fang,

Takashi Yamaguchi, Soomin C. Song, Nicolas X. Tritsch, Dayu Lin. Neuron.

Here they identified medial preoptic area estrogen receptor + (MPOAEsr1+) cells as an essential population for mediating maternal behaviors in female mice. These cells are preferentially activated prior to and during pup retrieval. Inactivation of MPOAEsr1+ cells specifically impaired approach and retrieval behaviors, whereas optogenetic activation acutely drove these behaviors, at least in part through efferent projections to the ventral tegmental area.

Read more here and here.

10. Interregional synaptic maps among engram cells underlie memory formation by Jun-Hyeok Choi, Su-Eon Sim, Ji-il Kim, Dong Il Choi, Jihae Oh, Sanghyun Ye, Jaehyun Lee, TaeHyun Kim, Hyoung-Gon Ko, Chae-Seok Lim, Bong-Kiun Kaang. Science.

They developed developed a c-fos transcription system, “dual-eGRASP”, to label CA3 to CA1 engram synapses, using non-engram cells as control synapses. This method allowed them to label two different sets of synapses and quantify their convergence on the same dendrites. After contextual fear conditioning in mice, the number and size of spines were increased on CA1 engram cells receiving input from CA3 engram cells. They found stronger connectivity between engram cells, and confirmed occluded LTP.

Read more here and here.

Plus two relevant reviews:

Neural Circuit Mechanisms of Social Behavior by Patrick Chen, Weizhe Hong. Neuron.

Genetic Dissection of Neural Circuits: A Decade of Progress by Liqun Luo, Edward M. Callaway, Karel Svoboda. Neuron.

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