Must read neural circuit papers in April 2017

     

I first began studying neural circuits in Ed Callaway’s lab at the Salk Institute, even before his group was doing viral tracing studies. To map functional circuits, we used electrophysiology of 1-2 neurons and glutamate uncaging with UV light, or photostimulation. Now photostimulation has transformed into optogenetics and neuroscientists have the ability to record from up to 1,000 neurons while animals freely behave, providing unprecedented insight into the neural circuits mediating complex behaviors and cognition.

I’m sharing a curated list of primary research papers, to help increase visibility of the amazing neuroscience research that’s published every month. For April, I’ve selected 7 neural circuit-related papers with relevance to cognition, memory, and neuropsychiatric disorders.

1. Engrams and circuits crucial for systems consolidation of a memory

by Takashi Kitamura, Sachie K. Ogawa, Dheeraj S. Roy, Teruhiro Okuyama, Mark D. Morrissey, Lillian M. Smith, Roger L. Redondo, & Susumu Tonegawa

 

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This tour de force out of RIKEN-MIT provides a comprehensive neural circuit mechanism for consolidation of memory, showing for the first time that memories initially form simultaneously in the hippocampus and the prefrontal cortex.

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2. Active dentate granule cells encode experience to promote the addition of adult- born hippocampal neurons

by Gregory W. Kirschen, Jia Shen, Mu Tian, Bryce Schroeder, Jia Wang, Guoming Man, Song Wu & Shaoyu Ge

 

Screen Shot 2017-04-25 at 9.17.09 AM.pngThis group from SUNY Stonybrook studied the neural circuit activity of the dorsal dentate gyrus during exploratory experiences known to promote survival of new hippocampal neurons. By coupling in vivo Ca2+ imaging of hippocampal neurons in freely behaving mice with a virtual reality system, they discovered that a new experience increased firing of active dentate granule neurons. Exploration in multiple novel virtual environments promoted dentate activation and enhanced the addition of new hippocampal neurons. Optogenetically silencing dentate granule cell activity during novel experiences perturbed experience-induced neuronal addition.

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3. Chemogenetic Interrogation of a Brain-wide Fear Memory Network in Mice

by Gisella Vetere, Justin W. Kenney, Lina M. Tran, Frances Xia, Patrick E. Steadman, John Parkinson, Sheena A. Josselyn, Paul W. Frankland

 

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Highly connected brain regions are more likely to be impacted in a range of brain disorders. This paper interrogates the effect of removing hub, or more highly connected brain regions, from fear memory networks. They found that inactivation of higher degree nodes was associated with greater memory consolidation deficits than similar inactivation of low degree nodes.

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4. Delay activity of specific prefrontal interneuron subtypes modulates memory-guided behavior

by Tsukasa Kamigaki & Yang Dan

 

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The authors applied in vivo Ca2+ imaging in behaving mice with bidirectional optogenetics while mice performed a memory-guided behavior. They saw distinct functional roles of 3 subtypes of dorsomedial prefrontal cortex GABAergic interneurons involved in short-term memory maintenance, suggesting they serve as a point of convergence for multiple inputs. Interestingly, they showed that activation of VIP neurons improved memory retention.

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5. Amygdala inputs to prefrontal cortex guide behavior amid conflicting cues of reward and punishment

by Anthony Burgos-Robles, Eyal Y Kimchi, Ehsan M Izadmehr, Mary Jane Porzenheim, William A Ramos-Guasp, Edward H Nieh, Ada C Felix-Ortiz, Praneeth Namburi, Christopher A Leppla, Kara N Presbrey, Kavitha K Anandalingam, Pablo A Pagan-Rivera, Melodi Anahtar, Anna Beyeler & Kay M Tye

 

Screen Shot 2017-05-01 at 12.31.31 PM.pngKay Tye’s group at MIT gave mice competing cues – a reward cue and a punishment, and then looked to see what neural circuits could mediate the conflicting behavior. They recorded neural activity from the basolateral nucleus of the amygdala (BLA) and prelimbic (PL) medial prefrontal cortex while animals either received a cue the mice had learned to associate with a shock (inducing fear) or a sucrose treat (reward). The authors saw a directionality in the neural circuit, indicating that BLA was more likely to activate PL in a correlated fashion during the fear-related cue. The authors then used optogenetics & chemogenetics to show the bottom-up BLA→ PL projections can drive behavior during fear retrieval.

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6. Medial Entorhinal Cortex Selectively Supports Temporal Coding by Hippocampal Neurons

by Nick T.M. Robinson, James B. Priestley, Jon W. Rueckemann, Aaron D. Garcia, Vittoria A. Smeglin, Francesca A. Marino, Howard Eichenbaum

 

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Memory formation relies on precise temporal and spatial coding of information in the hippocampus. Here they interrogate the role of upstream cortical input using optogenetics and inactivation of medial entorhinal cortex. They looked at the effects of the manipulation on temporal, spatial and object coding by hippocampal CA1 neurons. They saw that medial entorhinal inactivation produced a specific deficit in temporal coding in CA1 and resulted in significant impairment in memory across a temporal delay. Read more here

 

 

7. Pcdhac2 is required for axonal tiling and assembly of serotonergic circuitries in mice.

by Weisheng Chen, PhD, Chiamaka Nwakeze, Christine Denny, PhD, Sean O’Keeffe, Michael Rieger, PhD, George Mountoufaris, PhD, Amy Kirner, Joseph Dougherty, PhD, René Hen, PhD, Qiang Wu, PhD, and Tom Maniatis, PhD.

 

hc_serotonergic_mutant_1.jpgSerotonin imbalance is linked to neuropsychiatric disorders. Dr. Maniatis and his team examined the function of a group of genes called clustered protocadherins, or Pcdhs, in the wiring of serotonergic neurons. Here they show that conditional deletion of the mouse protocadherin α (Pcdhα) gene cluster in serotonergic neurons resulted in disorganized serotonergic projections and a disruption in local axonal tiling, the precise, evenly-spaced pattern usually seen. Moreover, the mice exhibited depression-like behaviors. Genetic dissection and expression profiling pinpointed a single gene within the Pcdh cluster, Pcdhαc2, which is the only Pcdhα isoform expressed in serotonergic neurons.

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About The Author

Jami is a neuroscientist and writer who is passionate about the communication of scientific research. She earned her PhD in Ed Callaway's lab in a joint program between The Salk Institute & UCSD. She was a postodoctoral fellow in Cori Bargmann's lab, and an editor for neuroscience publications at PLOS Biology.