The purpose of the Seminar Series Journal Club is to familiarize students and faculty with the most important scientific contributions of each seminar speaker in advance of the week's seminar. This preparation allows for better comprehension of the weekly seminar topics and a more robust question-and-answer session with the invited speaker. 

The Seminar Journal Club is also a for-credit course, required for 1st and 2nd year students enrolled in the neuroscience graduate program. Course directors are Drs. Jeannie Chin and Javier Medina. The course runs from Term 2 through Term 4. The Journal Clubs that fall before, in between, or after school terms are organized by invited speaker’s host lab. 

Seminar Series Journal Club meets on Wednesdays from noon - 1 p.m. in room S740 in Smith. Lunch is provided.

Seminar Journal Club, September through November 2018

Seminar journal club review papers are linked here.

Sept. 5, 2018: Gabriel de Erausquin 

Dr. de Erausquin will be mainly presenting unpublished data. The following two journal papers, selected by Dr. de Erausquin, will provide the necessary background in preparation for his Friday seminar. 

Parkinsonian motor impairment predicts personality domains related to genetic risk and treatment outcomes in schizophrenia. Molina JL, Calvó M, Padilla E, et al. Parkinsonian motor impairment predicts personality domains related to genetic risk and treatment outcomes in schizophrenia. NPJ Schizophrenia. 2017;3:16036-. doi:10.1038/npjschz.2016.36.

PGMRA: a web server for (phenotype genotype) many-to-many relation analysis in GWAS

Arnedo, Javier et al. “PGMRA: A Web Server for (phenotype × Genotype) Many-to-Many Relation Analysis in GWAS.” Nucleic Acids Research 41.Web Server issue (2013): W142–W149. PMC. Web. 21 Aug. 2018.

Oct. 3, 2018: Jack L. Feldman, Ph.D.

"The peptidergic control circuit for sighing", published in Nature (volume 530, pages 293-297) on Feb. 8, 2016 - doi:10.1038/nature16964. Authors: Peng Li, Wiktor A. Janczewski, Kevin Yackle, Kaiwen Kam, Silvia Pagliardini, Mark A. Krasnow & Jack L. Feldman.

This is not an open access journal article. Neuroscience Department members can request it via TMC Online Library. It will be also provided as a PDF to all members of the neuroscience department as we get closer to the journal club date.

Oct. 17, 2018: Jill Leutgeb, Ph.D.

"Dentate network activity is necessary for spatial working memory by supporting CA3 sharp-wave ripple generation and prospective firing of CA3 neurons", published in Nature Neuroscience (Vol 21, pages 258-269) on Jan. 15, 2018.  PubMed - NCBI PMID: 29335604.   

Dentate Network Activity is Necessary for Spatial Working Memory by Supporting CA3 Sharp-wave Ripple Generation and Prospective Firing of CA3 NeuronsSasaki, T., Piatti, V. C., Hwaun, E., Ahmadi, S., Lisman, J. E., Leutgeb, S., & Leutgeb, J. K. (2018). Nature Neuroscience, 21(2), 258–269. http://doi.org/10.1038/s41593-017-0061-5

Oct. 31, 2018: Aaron DiAntonio, M.D. Ph.D.

Note that due to the conflict with SfN conference in San Diego, this journal club will meet a week early, on October 31st, instead of Wednesday, Nov 7.

The SARM1 Toll/Interleukin-1 Receptor Domain Possesses Intrinsic NAD+ Cleavage Activity that Promotes Pathological Axonal Degeneration.  Essuman K., Summers D.W., Sasaki Y., Mao X., DiAntonio A., Milbrandt J. (2017). Neuron, March 22 2017, 93  (6) , pp. 1334-1343.e5.

Nov. 14, 2018: Laura Ranum, Ph.D.

At her seminar on November 16th, Dr. Ranum will talk about RAN translation and discuss some new unpublished data on therapeutic strategies to target RAN proteins and to block RAN translation. There are two journal articles that she chose as most helpful in preparation for her lecture: 

C9orf72 BAC Mouse Model with Motor Deficits and Neurodegenerative Features of ALS/FTD. Yuanjing Liu, Amrutha Pattamatta, Tao Zu, Tammy Reid, Olgert Bardhi, David R. Borchelt, Anthony T. Yachnis, Laura P.W. Ranum. Neuron, May 4 2016, 90 (3), pp. 521-534. 

Non-ATG–initiated translation directed by microsatellite expansions. Tao Zu, Brian Gibbens, Noelle S. Doty, Mário Gomes-Pereira, Aline Huguet, Matthew D. Stone, Jamie Margolis, Mark Peterson, Todd W. Markowski, Melissa A. C. Ingram, Zhenhong Nan, Colleen Forster, Walter C. Low, Benedikt Schoser, Nikunj V. Somia, H. Brent Clark, Stephen Schmechel, Peter B. Bitterman, Geneviève Gourdon, Maurice S. Swanson, Melinda Moseley, Laura P. W. Ranum.  PNAS, January 4, 2011 VOl108 (1) 260-265.  

Nov. 28, 2018: Elizabeth Hillman, Ph.D.

Swept confocally-aligned planar excitation (SCAPE) microscopy for high speed volumetric imaging of behaving organisms.  Bouchard MB, Voleti V, Mendes CS, Lacefield C, Grueber WB, Mann RS, Bruno RM, Hillman EM. Nature Photonics, February 2015, 9(2): 113-119. DOI:10.1038/nphoton.2014.323 

Seminar Journal Club, December 2018 through February 2019

Seminar journal club review papers are linked here.

Dec. 5: Jesse Goldberg, Ph.D. 

Dopamine neurons encode performance error in singing birds.Vikram Gadagkar, Pavel A. Puzerey, Ruidong Chen, Eliza Baird-Daniel, Alexander R. Farhang, Jesse H. Goldberg.  Science, Dec 2016: Vol. 354 (6317), pp. 1278-1282. 
DOI: 10.1126/science.aah6837.

In Brief: Many behaviors are learned through trial and error by matching performance to internal goals. Yet neural mechanisms of performance evaluation remain poorly understood. We recorded basal ganglia–projecting dopamine neurons in singing zebra finches as we controlled perceived song quality with distorted auditory feedback. Dopamine activity was phasically suppressed after distorted syllables, consistent with a worse-than-predicted outcome, and was phasically activated at the precise moment of the song when a predicted distortion did not occur, consistent with a better-than-predicted outcome. Error response magnitude depended on distortion probability. Thus, dopaminergic error signals can evaluate behaviors that are not learned for reward and are instead learned by matching performance outcomes to internal goals.

Jan. 9, 2019: James Knierim, Ph.D. 

Egocentric coding of external items in the lateral entorhinal cortex.  Cheng Wang, Xiaojing Chen, Heekyung Lee, Sachin S. Deshmukh, D. Yoganarasimha, Francesco Savelli, James J. Knierim.  Science, Nov 23 2018: Vol. 362 (6417), pp. 945-949.
DOI: 10.1126/science.aau4940.

In Brief: Episodic memory, the conscious recollection of past events, is typically experienced from a first-person (egocentric) perspective. The hippocampus plays an essential role in episodic memory and spatial cognition. Although the allocentric nature of hippocampal spatial coding is well understood, little is known about whether the hippocampus receives egocentric information about external items. Authors recorded in rats the activity of single neurons from the lateral entorhinal cortex (LEC) and medial entorhinal cortex (MEC), the two major inputs to the hippocampus. Many LEC neurons showed tuning for egocentric bearing of external items, whereas MEC cells tended to represent allocentric bearing. These results demonstrate a fundamental dissociation between the reference frames of LEC and MEC neural representations.

Jan. 16, 2019: Baljit Khakh, Ph.D.

Reducing Astrocyte Calcium Signaling In Vivo Alters Striatal Microcircuits and Causes Repetitive Behavior. Yu et al., 2018, Neuron 99, 1170–1187. September 19, 2018. 
doi: 10.1016/j.neuron.2018.08.015. 

In Brief: The Khakh laboratory evaluated the consequences of genetically attenuating astrocyte calcium signaling in the adult mouse striatum in vivo. They discovered excessive self-grooming phenotypes, the mechanisms of which were explored at the molecular, cellular, and in vivo levels.

Jan. 23, 2019: Jonathan Ting, Ph.D.

h-Channels Contribute to Divergent IntrinsicMembrane Properties of Supragranular Pyramidal Neurons in Human versusMouse Cerebral Cortex Kalmbach et al., 2018, Neuron 100, 1194–1208. December 5, 2018.

In Brief: h-channel-related gene expression is more prominent in human than mouse supragranular cortex. Consequently, h-channels contribute to supragranular pyramidal neuron physiology more in human than mouse neocortex. These differences produce fundamental differences in synaptic integration in human supragranular pyramidal neurons.

Feb. 20, 2019: Amita Sehgal, Ph.D. 

A Circadian Clock in the Blood-Brain Barrier Regulates Xenobiotic Efflux Zhang et al., 2018, Cell 173, 130–139. March 22, 2018. 

In Brief: The circadian clock influences the permeability of the blood-brain barrier, affecting drug efficacy at different times of day.

Feb. 27, 2019: Lisa Goodrich, Ph.D.

Sensory Neuron Diversity in the Inner Ear is Shaped by Activity Shrestha et al (2018). Cell 174(5):1229-1246. 
doi: 10.1016/j.cell.2018.07.007.

In Brief: Single cell analyses of mouse type I spiral ganglion neurons characterize three functionally distinct subtypes, revealing insights into auditory processing with implications for treating congenital deafness.

Seminar Journal Club, March through April 30, 2019

Seminar journal club review papers are linked here.

March 6, 2019: Sally Temple, Ph.D.

Non-monotonic Changes in Progenitor Cell Behavior and Gene Expression during Aging of the Adult V-SVZ Neural Stem Cell Niche. Apostolopoulou et al., Stem Cell Reports 9, 1-17, December 12, 2017 https://doi.org/10.1016/j.stemcr.2017.10.005

In Brief: Neural stem cell activity in the ventricular-subventricular zone (V-SVZ) decreases with aging, thought to occur by a unidirectional decline. However, by analyzing the V-SVZ transcriptome of male mice at 2, 6, 18, and 22 months, authors found that most of the genes that change significantly over time show a reversal of trend, with a maximum or minimum expression at 18 months. In vivo, MASH1+ progenitor cells decreased in number and proliferation between 2 and 18 months but increased between 18 and 22 months. Time-lapse lineage analysis of 944 V-SVZ cells showed that age-related declines in neurogenesis were recapitulated in vitro in clones. However, activated type B/type C cell clones divide slower at 2 to 18 months, then unexpectedly faster at 22 months, with impaired transition to type A neuroblasts. Findings indicate that aging of the V-SVZ involves significant non-monotonic changes that are programmed within progenitor cells and are observable independent of the aging niche.

March 13, 2019: Casper Hoogenraad, Ph.D.

Dynamic Palmitoylation Targets MAP6 to the Axon to Promote Microtubule Stabilization during Neuronal Polarization
Tortosa et al., 2017, Neuron 94, 809–825. May 17, 2017.  http://dx.doi.org/10.1016/j.neuron.2017.04.042. 

In Brief: Tortosa et al. show that MAP6 redistributes from Golgi and secretory vesicles to axonal microtubules during neuronal polarization. Palmitoylation cycles control MAP6 membrane-microtubule shuttling. The authors also demonstrate the importance of MAP6 for microtubule stabilization, organelle trafficking, and axon maturation. 

March 20, 2019: Cagla Eroglu, Ph.D.

Astrocytic neuroligins control astrocyte morphogenesis and synaptogenesis. Jeff A. Stogsdill et al. Nature 551, 192–197. November 9, 2017. doi: 10.1038/nature24638

In brief: Astrocytes are complex glial cells with numerous fine cellular processes that infiltrate the neuropil and interact with synapses. The mechanisms that control the establishment of astrocyte morphology are unknown, and it is unclear whether impairing astrocytic infiltration of the neuropil alters synaptic connectivity. Authors show that astrocyte morphogenesis in the mouse cortex depends on direct contact with neuronal processes and occurs in parallel with the growth and activity of synaptic circuits. Their findings highlight a previously undescribed mechanism of action for neuroligins and link astrocyte morphogenesis to synaptogenesis. Because neuroligin mutations have been implicated in various neurological disorders, these findings also point towards an astrocyte-based mechanism of neural pathology. 

March 27: Jeanne Paz, Ph.D.

Augmented Reticular Thalamic Bursting and Seizures in Scn1a-Dravet Syndrome. Stefanie Ritter-Makinson et al. Cell Reports, Vol. 26, Issue 1, January 2, 2019, Pages 54-64. doi: 10.1016/j.celrep.2018.12.018

In Brief: In a mouse model of Dravet syndrome (DS) resulting from voltage-gated sodium channel deficiency, Ritter-Makinson et al. find that inhibitory neurons of the reticular thalamic nucleus are paradoxically hyperexcitable due to compensatory
reductions in a potassium SK current. Boosting this SK current treats nonconvulsive seizures in DS mice.

April 3: Jacqueline Burré, Ph.D.

Mechanism-based rescue of Munc18-1 dysfunction in varied encephalopathies by chemical chaperones. Noah Guy Lewis Guiberson et al. Nature Communications, (2018) 9:3986.
doi: 10.1038/s41467-018-06507-4.

In Brief: Heterozygous de novo mutations in the neuronal protein Munc18-1 are linked to epilepsies, intellectual disability, movement disorders, and neurodegeneration. These devastating diseases have a poor prognosis and no known cure, due to lack of understanding of the underlying disease mechanism. To determine how mutations in Munc18-1 cause disease, the authors
used newly generated S. cerevisiae strains, C. elegans models, and conditional Munc18-1 knockout mouse neurons expressing wild-type or mutant Munc18-1, as well as in vitro studies. The authors  find that at least five disease-linked missense mutations of Munc18-1 result in destabilization and aggregation of the mutant protein. Aggregates of mutant Munc18-1 incorporate wild-type Munc18-1, depleting functional Munc18-1 levels beyond hemizygous levels. They demonstrate that the three chemical chaperones 4-phenylbutyrate, sorbitol, and
trehalose reverse the deficits caused by mutations in Munc18-1 in vitro and in vivo in multiple models, offering a novel strategy for the treatment of varied encephalopathies. 

April 10: Qingchun Tong, Ph.D.

There will be no journal club associated with this seminar.  

April 17: Simon Peron, Ph.D.

A Cellular Resolution Map of Barrel Cortex Activity during Tactile Behavior.  Simon P. Peron et al. Neuron, (2015) 86 (3): 783-799. doi: 10.1016/j.neuron.2015.03.027

In Brief: Peron et al. comprehensively sample activity in superficial barrel cortex of behaving mice using two-photon calcium imaging. They demonstrate sparse and spatially intermingled representations of multiple tactile features and show that these representations are stable during learning.

April 24, 2019: Daniela Schiller, Ph.D. 

Attenuating Neural Threat Expression with Imagination.  Reddan et al. Neuron (2018) 100 (4): 994-1005. doi: 10.1016/j.neuron.2018.10.047 

In Brief: Reddan et al. demonstrate that threat responses can be extinguished through imagined simulations of the conditioned stimuli. Like real extinction, imagined extinction engages the ventromedial prefrontal cortex, amygdala, and related perceptual cortices. Nucleus accumbens activity predicts an individual’s ability to successfully extinguish via imagination.

Seminar Journal Club, May 1 - 31,  2019 

Seminar journal club review papers are linked here.

May 1, 2019: Laura Feltri, M.D.

Altered Trafficking and Processing of GALC Mutants Correlates with Globoid Cell Leukodystrophy Severity. Shin et al. J. Neurosci. (2016);  36(6): 1858 –1870. doi: 10.1523/JNEUROSCI.3095-15.2016. 

In Brief: Globoid cell leukodystrophy (GLD, Krabbe disease) is diagnosed by measuring galactosylceramidase (GALC) activity and DNAanalysis. However, genotype and phenotype often do not correlate due to considerable clinical variability, even for the same mutation, for unknown reasons. Shin et al. found that altered trafficking to the lysosome and processing of GALC correlates with GLD severity and is modulated bycis-polymorphisms. Current diagnosis of GLD is based on GALC activity of total cell lysates from blood, which does not discriminate whether the activity comes from the lysosome or other subcellular organelles. Measurement of GALC activity in lysosomes may predict which infants are at high risk for the infantile phenotype while distinguishing other children who will develop later-onset phenotypes without onset of symptoms for years.

May 8, 2019: Michelle Monje, M.D. Ph.D.

Targeting neuronal activity-regulated neuroligin-3 dependency in high-grade glioma. Venkatesh et al. Nature (2017); 549 (7673): 533-537. doi: 10.1038/nature24014

In Brief: High-grade gliomas (HGG) are a devastating group of cancers, representing the leading cause of brain tumor-related death in both children and adults. Therapies aimed at mechanisms intrinsic to the glioma cell have translated to only limited success; effective therapeutic strategies will need to also target elements of the tumor microenvironment that promote glioma progression. The authors recently demonstrated that neuronal activity robustly promotes the growth of a range of molecularly and clinically distinct HGG types, including adult glioblastoma (GBM), anaplastic oligodendroglioma, pediatric GBM, and diffuse intrinsic pontine glioma (DIPG). An important mechanism mediating this neural regulation of brain cancer is activity-dependent cleavage and secretion of the synaptic molecule neuroligin-3 (NLGN3), which promotes glioma proliferation through the PI3K-mTOR pathway. However, neuroligin-3 necessity to glioma growth, proteolytic mechanism of secretion and further molecular consequences in glioma remain to be clarified. Venkatesh et al. demonstrate a striking dependence of HGG growth on microenvironmental neuroligin-3, elucidate signaling cascades downstream of neuroligin-3 binding in glioma and determine a therapeutically targetable mechanism of secretion. Patient-derived orthotopic xenografts of pediatric GBM, DIPG and adult GBM fail to grow in Nlgn3 knockout mice. Neuroligin-3 stimulates numerous oncogenic pathways, including early focal adhesion kinase activation upstream of PI3K-mTOR, and induces transcriptional changes including upregulation of numerous synapse-related genes in glioma cells. Neuroligin-3 is cleaved from both neurons and oligodendrocyte precursor cells via the ADAM10 sheddase. ADAM10 inhibitors prevent release of neuroligin-3 into the tumor microenvironment and robustly block HGG xenograft growth. This work defines a promising strategy for targeting neuroligin-3 secretion, which could prove transformative for HGG therapy.

May 15, 2019: Carlos Brody, Ph.D

Posterior parietal cortex represents sensory history and mediates its effects on behaviour Akrami et al. Nature (2018) ; 000: 1-5. 
doi:10.1038/nature25510

In Brief: Many models of cognition and of neural computations posit the use and estimation of prior stimulus statistics 1–4: it has long been known that working memory and perception are strongly impacted by previous sensory experience, even when that sensory history is not relevant to the current task at hand. Nevertheless, the neural mechanisms and regions of the brain that are necessary for computing and using such prior experience are unknown. Authors report that the posterior parietal cortex (PPC) is a critical locus for the representation and use of prior stimulus information. Their research suggests a tight link between behavior and PPC representations of stimulus history. Their results indicate that the PPC is a central component in the processing of sensory-stimulus history, and could enable further neurobiological investigation of long-standing questions regarding how perception and working memory are affected by prior sensory information.