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  1. Article ; Online: Extinction trial spacing across days differentially impacts fear regulation in adult and adolescent male mice.

    Gerhard, Danielle M / Meyer, Heidi C

    Neurobiology of learning and memory

    2021  Volume 186, Page(s) 107543

    Abstract: Fear regulation changes as a function of age and adolescence is a key developmental period for the continued maturation of fear neural circuitry. A consistent finding in the literature is diminished extinction retention in adolescents. However, these ... ...

    Abstract Fear regulation changes as a function of age and adolescence is a key developmental period for the continued maturation of fear neural circuitry. A consistent finding in the literature is diminished extinction retention in adolescents. However, these studies often directly compare adolescents to adults using a single protocol and therefore provide little insight into learning parameters that improve adolescent fear regulation. Studies in adults highlight the benefits of spaced learning over massed learning. These findings have been extended to fear regulation, with adult rodents exhibiting improved extinction learning and retention when cues are distributed over days versus a single session. However, similar studies have not been performed in adolescents. Here, we systematically examine the impact of trial spacing across days on fear regulation. Adolescent or adult male mice were exposed to one of three extinction paradigms that presented the same number of trials but differed in the temporal distribution of trials across days (one day, two days, or four days). We found that introducing consolidation events into the protocol improves adult extinction learning and short-term extinction retention but these effects disappear after two weeks. For adolescents, all three protocols were comparably effective in reducing freezing across extinction training and improved retention at both short-term and long-term fear recall time points relative to extinction-naive mice. These findings suggest that extinction protocols that incorporate consolidation events are optimal for adults but additional booster training may be required for enduring efficacy. In contrast, protocols incorporating either massed or spaced presentations show immediate and enduring benefits for adolescents.
    MeSH term(s) Animals ; Extinction, Psychological/physiology ; Fear/physiology ; Learning/physiology ; Male ; Mice ; Time Factors
    Language English
    Publishing date 2021-11-05
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 1223366-3
    ISSN 1095-9564 ; 1074-7427
    ISSN (online) 1095-9564
    ISSN 1074-7427
    DOI 10.1016/j.nlm.2021.107543
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Developmental age and fatty acid amide hydrolase genetic variation converge to mediate fear regulation in female mice.

    Gerhard, Danielle M / Tse, Nathaniel / Lee, Francis S / Meyer, Heidi C

    Developmental psychobiology

    2023  Volume 65, Issue 6, Page(s) e22409

    Abstract: Anxiety disorders are more prevalent in females than in males, yet a majority of basic neuroscience studies are performed in males. Furthermore, anxiety disorders peak in prevalence during adolescence, yet little is known about neurodevelopmental ... ...

    Abstract Anxiety disorders are more prevalent in females than in males, yet a majority of basic neuroscience studies are performed in males. Furthermore, anxiety disorders peak in prevalence during adolescence, yet little is known about neurodevelopmental trajectories of fear expression, particularly in females. To examine these factors, we fear conditioned juvenile, adolescent, and adult female mice and exposed them to fear extinction and a long-term recall test. For this, we used knock-in mice containing a common human mutation in the gene for fatty acid amide hydrolase (FAAH), the primary catabolic enzyme for the endocannabinoid anandamide (FAAH-IN). This mutation has been shown to impart a low-anxiety phenotype in humans, and in rodents relative to their wild-type littermates. We find an impact of the FAAH polymorphism on developmental changes in fear behavior. Specifically, the FAAH polymorphism appears to induce a state of hypervigilance (increased fear) during adolescence. We also used markerless pose estimation software to classify alternative behaviors outside of freezing. These analyses revealed age differences in vigilance to indicators of threat and in the propensity of mice to explore an aversive environment, though genotypic differences were minimal. These findings address a gap in the literature regarding developmental patterns of fear learning and memory as well as the mechanistic contributions of the endocannabinoid system in females.
    MeSH term(s) Animals ; Female ; Humans ; Male ; Mice ; Endocannabinoids ; Extinction, Psychological ; Fear ; Polymorphism, Genetic
    Chemical Substances Endocannabinoids ; fatty-acid amide hydrolase (EC 3.5.1.-)
    Language English
    Publishing date 2023-08-07
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 4107-5
    ISSN 1098-2302 ; 0012-1630
    ISSN (online) 1098-2302
    ISSN 0012-1630
    DOI 10.1002/dev.22409
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Sex-Specific Molecular Changes in Depression.

    Gerhard, Danielle M / Duman, Ronald S

    Biological psychiatry

    2018  Volume 84, Issue 1, Page(s) 2–4

    MeSH term(s) Depression ; Depressive Disorder ; Female ; Humans ; Male ; Sex Characteristics
    Language English
    Publishing date 2018-07-11
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Comment
    ZDB-ID 209434-4
    ISSN 1873-2402 ; 0006-3223
    ISSN (online) 1873-2402
    ISSN 0006-3223
    DOI 10.1016/j.biopsych.2018.05.005
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Reshaping the Depressed Brain: A Focus on Synaptic Health.

    Gerhard, Danielle M / Ross, David A

    Biological psychiatry

    2018  Volume 84, Issue 11, Page(s) e73–e75

    MeSH term(s) Antidepressive Agents/therapeutic use ; Brain/physiopathology ; Depressive Disorder/drug therapy ; Depressive Disorder/metabolism ; Depressive Disorder/physiopathology ; Humans ; Synapses/metabolism ; Treatment Outcome
    Chemical Substances Antidepressive Agents
    Language English
    Publishing date 2018-11-09
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 209434-4
    ISSN 1873-2402 ; 0006-3223
    ISSN (online) 1873-2402
    ISSN 0006-3223
    DOI 10.1016/j.biopsych.2018.09.028
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: An Adolescent Sensitive Period for Threat Responding: Impacts of Stress and Sex.

    Gerhard, Danielle M / Meyer, Heidi C / Lee, Francis S

    Biological psychiatry

    2020  Volume 89, Issue 7, Page(s) 651–658

    Abstract: Anxiety and fear-related disorders peak in prevalence during adolescence, a window of rapid behavioral development and neural remodeling. However, understanding of the development of threat responding and the underlying neural circuits remains limited. ... ...

    Abstract Anxiety and fear-related disorders peak in prevalence during adolescence, a window of rapid behavioral development and neural remodeling. However, understanding of the development of threat responding and the underlying neural circuits remains limited. Preclinical models of threat conditioning and extinction have provided an unparalleled glimpse into the developing brain. In this review we discuss mouse and rat studies on the development of threat response regulation, with a focus on the adolescent period. Evidence of nonlinear patterns of threat responding during adolescence and the continued development of the underlying circuitry is highly indicative of an adolescent sensitive period for threat response regulation. While we highlight literature in support of this unique developmental window, we also emphasize the need for causal studies to clarify the parameters defining such a sensitive period. In doing so, we explore how stress and biological sex affect the development and expression of threat response regulation during adolescence and beyond. Ultimately, a deeper understanding of how these factors interact with and affect developmental trajectories of learning and memory will inform treatment and prevention strategies for pediatric anxiety disorders.
    MeSH term(s) Adolescent ; Animals ; Anxiety Disorders ; Child ; Extinction, Psychological ; Fear ; Humans ; Learning ; Memory ; Mice ; Rats
    Language English
    Publishing date 2020-10-10
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 209434-4
    ISSN 1873-2402 ; 0006-3223
    ISSN (online) 1873-2402
    ISSN 0006-3223
    DOI 10.1016/j.biopsych.2020.10.003
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article: Rapid-Acting Antidepressants: Mechanistic Insights and Future Directions.

    Gerhard, Danielle M / Duman, Ronald S

    Current behavioral neuroscience reports

    2018  Volume 5, Issue 1, Page(s) 36–47

    Abstract: Purpose of review: Ketamine produces rapid (within hours) antidepressant actions, even in patients considered treatment resistant, and even shows promise for suicidal ideation. Here, we review current research on the molecular and cellular mechanisms of ...

    Abstract Purpose of review: Ketamine produces rapid (within hours) antidepressant actions, even in patients considered treatment resistant, and even shows promise for suicidal ideation. Here, we review current research on the molecular and cellular mechanisms of ketamine and other novel rapid-acting antidepressants, and briefly explore gender differences in the pathophysiology and treatment of MDD.
    Recent findings: Ketamine, an NMDA receptor antagonist, increases BDNF release and synaptic connectivity, opposing the deficits caused by chronic stress and depression. Efforts are focused on the development of novel rapid agents that produce similar synaptic and rapid antidepressant actions, but without the side effects of ketamine. The impact of gender on the response to ketamine and other rapid-acting antidepressants is in early stages of investigation.
    Summary: The discovery that ketamine produces rapid therapeutic actions for depression and suicidal ideation represents a major breakthrough and much needed alternative to currently available medications. However, novel fast acting agents with fewer side effects are needed, as well as elucidation of the efficacy of these rapid-acting antidepressants for depression in women.
    Language English
    Publishing date 2018-02-05
    Publishing country Switzerland
    Document type Journal Article
    ISSN 2196-2979
    ISSN 2196-2979
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Synaptic plasticity via receptor tyrosine kinase/G-protein-coupled receptor crosstalk

    Cristina Lao-Peregrin / Guoqing Xiang / Jihye Kim / Ipsit Srivastava / Alexandra B. Fall / Danielle M. Gerhard / Piia Kohtala / Daegeon Kim / Minseok Song / Mikel Garcia-Marcos / Joshua Levitz / Francis S. Lee

    Cell Reports, Vol 43, Iss 1, Pp 113595- (2024)

    1481  

    Abstract: Summary: Cellular signaling involves a large repertoire of membrane receptors operating in overlapping spatiotemporal regimes and targeting many common intracellular effectors. However, both the molecular mechanisms and the physiological roles of ... ...

    Abstract Summary: Cellular signaling involves a large repertoire of membrane receptors operating in overlapping spatiotemporal regimes and targeting many common intracellular effectors. However, both the molecular mechanisms and the physiological roles of crosstalk between receptors, especially those from different superfamilies, are poorly understood. We find that the receptor tyrosine kinase (RTK) TrkB and the G-protein-coupled receptor (GPCR) metabotropic glutamate receptor 5 (mGluR5) together mediate hippocampal synaptic plasticity in response to brain-derived neurotrophic factor (BDNF). Activated TrkB enhances constitutive mGluR5 activity to initiate a mode switch that drives BDNF-dependent sustained, oscillatory Ca2+ signaling and enhanced MAP kinase activation. This crosstalk is mediated, in part, by synergy between Gβγ, released by TrkB, and Gαq-GTP, released by mGluR5, to enable physiologically relevant RTK/GPCR crosstalk.
    Keywords CP: Cell biology ; CP: Neuroscience ; Biology (General) ; QH301-705.5
    Subject code 571
    Language English
    Publishing date 2024-01-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  8. Article ; Online: Author Correction: Ketamine disinhibits dendrites and enhances calcium signals in prefrontal dendritic spines.

    Ali, Farhan / Gerhard, Danielle M / Sweasy, Katherine / Pothula, Santosh / Pittenger, Christopher / Duman, Ronald S / Kwan, Alex C

    Nature communications

    2021  Volume 12, Issue 1, Page(s) 370

    Language English
    Publishing date 2021-01-08
    Publishing country England
    Document type Published Erratum
    ZDB-ID 2553671-0
    ISSN 2041-1723 ; 2041-1723
    ISSN (online) 2041-1723
    ISSN 2041-1723
    DOI 10.1038/s41467-020-20634-x
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article: Synaptic plasticity via receptor tyrosine kinase/G protein-coupled receptor crosstalk.

    Lao-Peregrin, Cristina / Xiang, Guoqing / Kim, Jihye / Srivastava, Ipsit / Fall, Alexandra B / Gerhard, Danielle M / Kohtala, Piia / Kim, Daegeon / Song, Minseok / Garcia-Marcos, Mikel / Levitz, Joshua / Lee, Francis S

    bioRxiv : the preprint server for biology

    2023  

    Abstract: Cellular signaling involves a large repertoire of membrane receptors operating in overlapping spatiotemporal regimes and targeting many common intracellular effectors. However, both the molecular mechanisms and physiological roles of crosstalk between ... ...

    Abstract Cellular signaling involves a large repertoire of membrane receptors operating in overlapping spatiotemporal regimes and targeting many common intracellular effectors. However, both the molecular mechanisms and physiological roles of crosstalk between receptors, especially those from different superfamilies, are poorly understood. We find that the receptor tyrosine kinase (RTK), TrkB, and the G protein-coupled receptor (GPCR), metabotropic glutamate receptor 5 (mGluR5), together mediate a novel form of hippocampal synaptic plasticity in response to brain-derived neurotrophic factor (BDNF). Activated TrkB enhances constitutive mGluR5 activity to initiate a mode-switch that drives BDNF-dependent sustained, oscillatory Ca
    Language English
    Publishing date 2023-08-28
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2023.08.28.555210
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Synaptic plasticity via receptor tyrosine kinase/G-protein-coupled receptor crosstalk.

    Lao-Peregrin, Cristina / Xiang, Guoqing / Kim, Jihye / Srivastava, Ipsit / Fall, Alexandra B / Gerhard, Danielle M / Kohtala, Piia / Kim, Daegeon / Song, Minseok / Garcia-Marcos, Mikel / Levitz, Joshua / Lee, Francis S

    Cell reports

    2023  Volume 43, Issue 1, Page(s) 113595

    Abstract: Cellular signaling involves a large repertoire of membrane receptors operating in overlapping spatiotemporal regimes and targeting many common intracellular effectors. However, both the molecular mechanisms and the physiological roles of crosstalk ... ...

    Abstract Cellular signaling involves a large repertoire of membrane receptors operating in overlapping spatiotemporal regimes and targeting many common intracellular effectors. However, both the molecular mechanisms and the physiological roles of crosstalk between receptors, especially those from different superfamilies, are poorly understood. We find that the receptor tyrosine kinase (RTK) TrkB and the G-protein-coupled receptor (GPCR) metabotropic glutamate receptor 5 (mGluR5) together mediate hippocampal synaptic plasticity in response to brain-derived neurotrophic factor (BDNF). Activated TrkB enhances constitutive mGluR5 activity to initiate a mode switch that drives BDNF-dependent sustained, oscillatory Ca
    MeSH term(s) Brain-Derived Neurotrophic Factor ; Receptor Protein-Tyrosine Kinases ; Signal Transduction/physiology ; Receptor, trkB/metabolism ; Receptors, G-Protein-Coupled ; Neuronal Plasticity/physiology
    Chemical Substances Brain-Derived Neurotrophic Factor ; Receptor Protein-Tyrosine Kinases (EC 2.7.10.1) ; Receptor, trkB (EC 2.7.10.1) ; Receptors, G-Protein-Coupled
    Language English
    Publishing date 2023-12-19
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 2649101-1
    ISSN 2211-1247 ; 2211-1247
    ISSN (online) 2211-1247
    ISSN 2211-1247
    DOI 10.1016/j.celrep.2023.113595
    Database MEDical Literature Analysis and Retrieval System OnLINE

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