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A Hypothalamic Midbrain Pathway Essential for Driving Maternal Behaviors

Fang, Yi-Ya; Yamaguchi, Takashi; Song, Soomin C; Tritsch, Nicolas X; Lin, Dayu
Maternal behaviors are essential for the survival of the young. Previous studies implicated the medial preoptic area (MPOA) as an important region for maternal behaviors, but details of the maternal circuit remain incompletely understood. Here we identify estrogen receptor alpha (Esr1)-expressing cells in the MPOA as key mediators of pup approach and retrieval. Reversible inactivation of MPOAEsr1+cells impairs those behaviors, whereas optogenetic activation induces immediate pup retrieval. In vivo recordings demonstrate preferential activation of MPOAEsr1+cells during maternal behaviors and changes in MPOA cell responses across reproductive states. Furthermore, channelrhodopsin-assisted circuit mapping reveals a strong inhibitory projection from MPOAEsr1+cells to ventral tegmental area (VTA) non-dopaminergic cells. Pathway-specific manipulations reveal that this projection is essential for driving pup approach and retrieval and that VTA dopaminergic cells are reliably activated during those behaviors. Altogether, this study provides new insight into the neural circuit that generates maternal behaviors.
PMCID:5890946
PMID: 29621487
ISSN: 1097-4199
CID: 3025802

Neuroscience: Past and Future [Editorial]

Jan, Lily; Botvinick, Matthew; Bradke, Frank; Lin, Dayu; Kosik, Kenneth S.; Jan, Yuh-Nung
Reflecting on when Neuron was launched and what the next 30 years may bring, neuroscientists share their excitement and visions for the future of the field.
ISI:000429192100005
ISSN: 0896-6273
CID: 3049132

Large-Scale CRISPR-Mediated Somatic Mutagenesis Identifies a Signaling Pathway that Guides Retinal Development

Minkina, Olga; Desplan, Claude
As the mammalian outer retina develops, rod and cone photoreceptors synapse with their respective bipolar cells. Sarin et al. (2018) develop a somatic CRISPR technique to determine how genes differentially expressed among the four cell types mediate outer retina development.
PMCID:5902020
PMID: 29621482
ISSN: 1097-4199
CID: 3154242

Utilization of Immunotherapy in Head and Neck Cancers Pre-Food and Drug Administration Approval of Immune Checkpoint Inhibitors [Meeting Abstract]

Wu, S. P. P.; Tam, M.; Gerber, N. K.; Li, Z.; Schmidt, B.; Persky, M.; Sanfilippo, N. J.; Tran, T.; Jacobson, A.; DeLacure, M.; Hu, K. S.; Persky, M.; Schreiber, D. P.; Givi, B.
ISI:000428145600179
ISSN: 0360-3016
CID: 3035562

Obstructive Sleep Apnea Severity Affects Amyloid Burden in Cognitively Normal Elderly: A Longitudinal Study

Sharma, Ram A; Varga, Andrew W; Bubu, Omonigho M; Pirraglia, Elizabeth; Kam, Korey; Parekh, Ankit; Wohlleber, Margaret; Miller, Margo D; Andrade, Andreia; Lewis, Clifton; Tweardy, Samuel; Buj, Maja; Yau, Po L; Sadda, Reem; Mosconi, Lisa; Li, Yi; Butler, Tracy; Glodzik, Lidia; Fieremans, Els; Babb, James S; Blennow, Kaj; Zetterberg, Henrik; Lu, Shou E; Badia, Sandra G; Romero, Sergio; Rosenzweig, Ivana; Gosselin, Nadia; Jean-Louis, Girardin; Rapoport, David M; de Leon, Mony J; Ayappa, Indu; Osorio, Ricardo S
RATIONALE: Recent evidence suggests that Obstructive Sleep Apnea (OSA) may be a risk factor for developing Mild Cognitive Impairment and Alzheimer's disease. However, how sleep apnea affects longitudinal risk for Alzheimer's disease is less well understood. OBJECTIVE: To test the hypothesis that there is an association between severity of OSA and longitudinal increase in amyloid burden in cognitively normal elderly. METHODS: Data was derived from a 2-year prospective longitudinal study that sampled community-dwelling healthy cognitively normal elderly. Subjects were healthy volunteers between the ages of 55 to 90, were non-depressed and had a consensus clinical diagnosis of cognitively normal. CSF Amyloid beta was measured using ELISA. Subjects received Pittsburgh compound B Positron Emission Tomography scans following standardized procedures. Monitoring of OSA was completed using a home sleep recording device. MEASUREMENTS AND MAIN RESULTS: We found that severity of OSA indices (lnAHIall [F1,88=4.26, p<.05] and lnAHI4% [F1,87=4.36, p<.05]) were associated with annual rate of change of CSF Abeta42 using linear regression after adjusting for age, sex, BMI and ApoE4 status. LnAHIall and lnAHI4 were not associated with increases in ADPiB-mask most likely due to the small sample size although there was a trend for lnAHIall (F1,28=2.96, p=.09 and F1,28=2.32, n.s. respectively). CONCLUSION: In a sample of cognitively normal elderly, OSA was associated with markers of increased amyloid burden over the 2 year follow-up. Sleep fragmentation and/or intermittent hypoxia from OSA are likely candidate mechanisms. If confirmed, clinical interventions for OSA may be useful in preventing amyloid build-up in cognitively normal elderly.
PMCID:6020410
PMID: 29125327
ISSN: 1535-4970
CID: 2772892

SLEEP SPINDLE COUNT IN SUBSYNDROMAL DEPRESSED VS NORMAL ELDERLY: A PROTECTIVE EFFECT OF SLEEP SPINDLES? [Meeting Abstract]

Sharma, R. A.; Miller, M. D.; Kam, K.; Parekh, A.; Rivas, J.; Bubu, O. M.; Varga, A. W.; Iosifescu, D., V; Osorio, R. S.
ISI:000431183401175
ISSN: 1550-9109
CID: 3114152

Real-time particle filtering and smoothing algorithms for detecting abrupt changes in neural ensemble spike activity

Hu, Sile; Zhang, Qiaosheng; Wang, Jing; Chen, Zhe
Sequential change-point detection from time series data is a common problem in many neuroscience applications, such as seizure detection, anomaly detection, and pain detection. In our previous work (Chen et al., 2017, J. Neural Eng.), we have developed a latent state space model, known as Poisson linear dynamical system (PLDS), for detecting abrupt changes in neuronal ensemble spike activity. In online brain-machine interface (BMI) applications, a recursive filtering algorithm is used to track the changes in the latent variable. However, previous methods have restricted to Gaussian dynamical noise and have used Gaussian approximation for the Poisson likelihood. To improve the detection speed, we introduce non-Gaussian dynamical noise for modeling a stochastic jump process in the latent state space. To efficiently estimate the state posterior that accommodates non-Gaussian noise and non-Gaussian likelihood, we propose particle filtering and smoothing algorithms for the change-point detection problem. To speed up the computation, we implement the proposed particle filtering algorithms using advanced GPU (graphic processing unit) computing technology. We validate our algorithms using both computer simulations and experimental data for acute pain detection. Finally, we discuss several important practical issues in the context of real-time closed-loop BMI applications.
PMCID:5966736
PMID: 29357468
ISSN: 1522-1598
CID: 2929372

Future prospects and challenges for Alzheimer's disease drug development in the era of the NIA-AA Research Framework [Editorial]

Khachaturian, Ara S; Hayden, Kathleen M; Mielke, Michelle M; Tang, Yi; Lutz, Michael W; Gustafson, Deborah R; Kukull, Walter A; Mohs, Richard; Khachaturian, Zaven S
PMID: 29653605
ISSN: 1552-5279
CID: 3058942

eCurves: A Temporal Shape Encoding

Bernardis, Elena; Zhang, Yong; Konukoglu, Ender; Ou, Yangming; Javitz, Harold S; Axel, Leon; Metaxas, Dimitris; Desjardins, Benoit; Pohl, Kilian M
OBJECTIVE:This paper presents a framework for temporal shape analysis to capture the shape and changes of anatomical structures from three-dimensional+t(ime) medical scans. METHOD/METHODS:We first encode the shape of a structure at each time point with the spectral signature, i.e., the eigenvalues and eigenfunctions of the Laplace operator. We then expand it to capture morphing shapes by tracking the eigenmodes across time according to the similarity of their eigenfunctions. The similarity metric is motivated by the fact that small-shaped deformations lead to minor changes in the eigenfunctions. Following each eigenmode from the beginning to end results in a set of eigenmode curves representing the shape and its changes over time. RESULTS:We apply our encoding to a cardiac dataset consisting of series of segmentations outlining the right and left ventricles over time. We measure the accuracy of our encoding by training classifiers on discriminating healthy adults from patients that received reconstructive surgery for Tetralogy of Fallot (TOF). The classifiers based on our encoding significantly surpass deformation-based encodings of the right ventricle, the structure most impacted by TOF. CONCLUSION/CONCLUSIONS:The strength of our framework lies in its simplicity: It only assumes pose invariance within a time series but does not assume point-to-point correspondence across time series or a (statistical or physical) model. In addition, it is easy to implement and only depends on a single parameter, i.e., the number of curves.
PMCID:5732904
PMID: 28641243
ISSN: 1558-2531
CID: 3027102

18F-florbetapir Positron Emission Tomography-determined Cerebral beta-Amyloid Deposition and Neurocognitive Performance after Cardiac Surgery

Klinger, Rebecca Y; James, Olga G; Borges-Neto, Salvador; Bisanar, Tiffany; Li, Yi-Ju; Qi, Wenjing; Berger, Miles; Terrando, Niccola; Newman, Mark F; Doraiswamy, P Murali; Mathew, Joseph P; Weiner, Michael W; Aisen, Paul; Petersen, Ronald; Jack, Clifford R; Jagust, William; Trojanowki, John Q; Toga, Arthur W; Beckett, Laurel; Green, Robert C; Saykin, Andrew J;Shaw, Leslie M; Khachaturian, Zaven; Sorensen, Greg; Carrillo, Maria; Kuller, Lew; Raichle, Marc; Paul, Steven; Davies, Peter; Fillit, Howard; Hefti, Franz; Holtzman, David; Potter, William; Snyder, Peter; Schwartz, Adam; Montine, Tom; Thomas, Ronald G; Donohue, Michael; Walter, Sarah; Gessert, Devon; Sather, Tamie; Jiminez, Gus; Balasubramanian, Archana B; Mason, Jennifer; Sim, Iris; Harvey, Danielle; Bernstein, Matthew; Fox, Nick; Thompson, Paul; Schuff, Norbert; DeCArli, Charles; Borowski, Bret; Gunter, Jeff; Senjem, Matt; Vemuri, Prashanthi; Jones, David; Kantarci, Kejal; Ward, Chad; Koeppe, Robert A; Foster, Norm; Reiman, Eric M; Chen, Kewei; Mathis, Chet; Landau, Susan; Morris, John C; Cairns, Louis Nigel J; Franklin, Erin; Taylor-Reinwald, Lisa; Lee, Virginia; Korecka, Magdalena; Figurski, Michal; Crawford, Karen; Neu, Scott; Foroud, Tatiana M; Shen, Li; Faber, Kelley; Kim, Sungeun; Nho, Kwangsik; Thal, Lean; Thal, Leon; Buckholtz, Neil; Snyder, Peter J; Albert, Marilyn; Frank, Richard; Hsiao, John; Kaye, Jeffrey; Quinn, Joseph; Silbert, Lisa; Lind, Betty; Carter, Raina; Dolen, Sara; Schneider, Lon S; Pawluczyk, Sonia; Becerra, Mauricio; Teodoro, Liberty; Spann, Bryan M; Brewer, James; Vanderswag, Helen; Fleisher, Adam; Heidebrink, Judith L; Lord, Joanne L; Mason, Sara S; Albers, Colleen S; Knopman, David; Johnson, Kris; Doody, Rachelle S; Villanueva-Meyer, Javier; Pavlik, Valory; Shibley, Victoria; Chowdhury, Munir; Rountree, Susan; Dang, Mimi; Stern, Yaakov; Honig, Lawrence S; Bell, Karen L; Ances, Beau; Carroll, Maria; Creech, Mary L; Mintun, Mark A; Schneider, Stacy; Oliver, Angela; Marson, Daniel; Geldmacher, David; Love, Marissa Natelson; Griffith, Randall; Clark, David; Brockington, John; Roberson, Erik; Grossman, Hillel; Mitsis, Effie; Shah, Raj C; deToledo-Morrell, Leyla; Duara, Ranjan; Greig-Custo, Maria T; Barker, Warren; Onyike, Chiadi; D'Agostino, Daniel; Kielb, Stephanie; Sadowski, Martin; Sheikh, Mohammed O; Ulysse, Anaztasia; Gaikwad, Mrunalini; Petrella, Jeffrey R; Wong, Terence Z; Coleman, Edward; Arnold, Steven E; Karlawish, Jason H; Wolk, David A; Clark, Christopher M; Smith, Charles D; Jicha, Greg; Hardy, Peter; Sinha, Partha; Oates, Elizabeth; Conrad, Gary; Lopez, Oscar L; Oakley, MaryAnn; Simpson, Donna M; Porsteinsson, Anton P; Goldstein, Bonnie S; Makino, Kelly M; Ismail, M Saleem; Brand, Connie; Potkin, Steven G; Preda, Adrian; Nguyen, Dana; Womack, Kyle; Mathews, Dana; Quiceno, Mary; Levey, Allan I; Lah, James J; Cellar, Janet S; Burns, Jeffrey M; Swerdlow, Russell H; Brooks, William M; Apostolova, Liana; Tingus, Kathleen; Woo, Ellen; Silverman, Daniel H S; Lu, Po H; Bartzokis, George; Graff-Radford, Neill R; Parfitt, Francine; Poki-Walker, Kim; Farlow, Martin R; Hake, Ann Marie; Matthews, Brandy R; Brosch, Jared R; Herring, Scott; van Dyck, Christopher H; Carson, Richard E; MacAvoy, Martha G; Varma, Pradeep; Chertkow, Howard; Bergman, Howard; Hosein, Chris; Black, Sandra; Stefanovic, Bojana; Caldwell, Curtis; Hsiung, Robin; Mudge, Benita; Sossi, Vesna; Feldman, Howard; Assaly, Michele; Finger, Elizabeth; Pasternack, Stephen; Trost, Dick; Kertesz, Andrew; Bernick, Charles; Munic, Donna; Mesulam, Marek-Marsel; Rogalski, Emily; Lipowski, Kristine; Weintraub, Sandra; Bonakdarpour, Borna; Kerwin, Diana; Wu, Chuang-Kuo; Johnson, Nancy; Sadowsky, Carl; Villena, Teresa; Turner, Raymond Scott; Johnson, Kathleen; Reynolds, Brigid; Sperling, Reisa A; Johnson, Keith A; Marshall, Gad; Yesavage, Jerome; Taylor, Joy L; Lane, Barton; Rosen, Allyson; Tinklenberg, Jared; Sabbagh, Marwan N; Belden, Christine M; Jacobson, Sandra A; Sirrel, Sherye A; Kowall, Neil; Killiany, Ronald; Budson, Andrew E; Norbash, Alexander; Johnson, Patricia Lynn; Obisesan, Thomas O; Wolday, Saba; Allard, Joanne; Lerner, Alan; Ogrocki, Paula; Tatsuoka, Curtis; Fatica, Parianne; Fletcher, Evan; Maillard, Pauline; Olichney, John; DeCarli, Charles; Carmichael, Owen; Kittur, Smita; Borrie, Michael; Lee, T-Y; Bartha, Dr Rob; Asthana, Sanjay; Carlsson, Cynthia M; Tariot, Pierre; Burke, Anna; Milliken, Ann Marie; Trncic, Nadira; Reeder, Stephanie; Bates, Vernice; Capote, Horacio; Rainka, Michelle; Scharre, Douglas W; Kataki, Maria; Kelley, Brendan; Zimmerman, Earl A; Celmins, Dzintra; Brown, Alice D; Pearlson, Godfrey D; Blank, Karen; Anderson, Karen; Flashman, Laura A; Seltzer, Marc; Hynes, Mary L; Santulli, Robert B; Sink, Kaycee M; Gordineer, Leslie; Williamson, Jeff D; Garg, Pradeep; Watkins, Franklin; Ott, Brian R; Tremont, Geoffrey; Daiello, Lori A; Salloway, Stephen; Malloy, Paul; Correia, Stephen; Rosen, Howard J; Miller, Bruce L; Perry, David; Mintzer, Jacobo; Spicer, Kenneth; Bachman, David; Rachinsky, Irina; Rogers, John; Drost, Dick; Pomara, Nunzio; Hernando, Raymundo; Sarrael, Antero; Schultz, Susan K; Smith, Karen Ekstam; Koleva, Hristina; Nam, Ki Won; Shim, Hyungsub; Relkin, Norman; Chiang, Gloria; Lin, Michael; Ravdin, Lisa; Smith, Amanda; Ashok Raj, Balebail; Fargher, Kristin; Neylan, Thomas; Grafman, Jordan; Thomas, Ronald G; Davis, Melissa; Morrison, Rosemary; Hayes, Jacqueline; Finely, Shannon; Cairns, Nigel J; Householder, Erin; Crawford, Karen; Friedl, Karl; Fleischman, Debra; Arfanakis, Konstantinos; Varon, Daniel; Greig, Maria T; Martin, Kimberly S; Preda, Adrian; Massoglia, Dino; Brawman-Mintzer, Olga; Martinez, Walter; Behan, Kelly; Johnson, Sterling C; Fruehling, J Jay; Harding, Sandra; Peskind, Elaine R; Petrie, Eric C; Li, Gail; Furst, Ansgar J; Chao, Steven; Blumenthal, James A; Karhausen, Jorn A; Kertai, Miklos D; Podgoreanu, Mihai V; Stafford-Smith, Mark; Swaminathan, Madhav; Warner, David S; Funk, Bonita L; Balajonda, Narai; Brassard, Rachele; Cooter, Mary; Toulgoat-Dubois, Yanne; Waweru, Peter; Babyak, Michael A; Browndyke, Jeffrey N; Welsh-Bohmer, Kathleen A; Sketch, Michael H; Bennett, Ellen R; Graffagnino, Carmelo; Laskowitz, Daniel T; Strittmatter, Warren J; Collins, Kevin; Smigla, Greg; Shearer, Ian; D'Amico, Thomas A; Daneshmand, Mani A; Gaca, R Jeffrey G; Glower, Donald D; Haney, Jack; Harpole, R David; Hartwig, Mathew G; Hughes, G Chad; Klapper, Jacob A; Lin, Shu S; Lodge, Andrew J; Milano, Carmelo A; Plichta, Ryan P; Schroeder, Jacob N; Smith, Peter K; Tong, Betty C
BACKGROUND:Amyloid deposition is a potential contributor to postoperative cognitive dysfunction. The authors hypothesized that 6-week global cortical amyloid burden, determined by F-florbetapir positron emission tomography, would be greater in those patients manifesting cognitive dysfunction at 6 weeks postoperatively. METHODS:Amyloid deposition was evaluated in cardiac surgical patients at 6 weeks (n = 40) and 1 yr (n = 12); neurocognitive function was assessed at baseline (n = 40), 6 weeks (n = 37), 1 yr (n = 13), and 3 yr (n = 9). The association of 6-week amyloid deposition with cognitive dysfunction was assessed by multivariable regression, accounting for age, years of education, and baseline cognition. Differences between the surgical cohort with cognitive deficit and the Alzheimer's Disease Neuroimaging Initiative cohorts (normal and early/late mild cognitive impairment) was assessed, adjusting for age, education, and apolipoprotein E4 genotype. RESULTS:The authors found that 6-week abnormal global cortical amyloid deposition was not associated with cognitive dysfunction (13 of 37, 35%) at 6 weeks postoperatively (median standard uptake value ratio [interquartile range]: cognitive dysfunction 0.92 [0.89 to 1.07] vs. 0.98 [0.93 to 1.05]; P = 0.455). In post hoc analyses, global cortical amyloid was also not associated with cognitive dysfunction at 1 or 3 yr postoperatively. Amyloid deposition at 6 weeks in the surgical cohort was not different from that in normal Alzheimer's Disease Neuroimaging Initiative subjects, but increased over 1 yr in many areas at a rate greater than in controls. CONCLUSIONS:In this study, postoperative cognitive dysfunction was not associated with 6-week cortical amyloid deposition. The relationship between cognitive dysfunction and regional amyloid burden and the rate of postoperative amyloid deposition merit further investigation.
PMCID:5849499
PMID: 29389750
ISSN: 1528-1175
CID: 2994312