Archives

  • 2018-07
  • 2018-10
  • 2018-11
  • 2019-04
  • 2019-05
  • 2019-06
  • 2019-07
  • 2019-08
  • 2019-09
  • 2019-10
  • 2019-11
  • 2019-12
  • 2020-01
  • 2020-02
  • 2020-03
  • 2020-04
  • 2020-05
  • 2020-06
  • 2020-07
  • 2020-08
  • 2020-09
  • 2020-10
  • 2020-11
  • 2020-12
  • 2021-01
  • 2021-02
  • 2021-03
  • 2021-04
  • 2021-05
  • 2021-06
  • 2021-07
  • 2021-08
  • 2021-09
  • 2021-10
  • 2021-11
  • 2021-12
  • 2022-01
  • 2022-02
  • 2022-03
  • 2022-04
  • 2022-05
  • 2022-06
  • 2022-07
  • 2022-08
  • 2022-09
  • 2022-10
  • 2022-11
  • 2022-12
  • 2023-01
  • 2023-02
  • 2023-03
  • 2023-04
  • 2023-05
  • 2023-06
  • 2023-07
  • 2023-08
  • 2023-09
  • 2023-10
  • 2023-11
  • 2023-12
  • 2024-01
  • 2024-02
  • 2024-03
  • kinase inhibitors Given the prominence of midbrain dopaminer

    2018-10-25

    Given the prominence of midbrain dopaminergic projections to the ventral striatum, as well as prefrontal kinase inhibitors (Haber et al., 2000, 2006; Sesack and Grace, 2010), brief consideration of mesolimbic dopaminergic development is warranted. The concentration of dopamine receptors throughout the striatum increases during the transition to adolescence in rodents, but interestingly declines post adolescence across the striatum except in the NAcc, where levels remain high throughout adulthood (Teicher et al., 1995). Relatedly, pre-adolescent increases in dopaminergic synthesis decline between adolescence and early adulthood in the striatum except for in the NAcc (Andersen et al., 1997), and firing rates of VTA dopaminergic neurons are more rapid in adolescent than adult rats (McCutcheon et al., 2012). Less PFC, NAcc and amygdala innervation of the VTA in adolescent as compared to young adult rats (Yetnikoff et al., 2014), in conjunction with ventral striatal developmental patterns likely underlies oft observed increases in appetitive behaviors during adolescence across species (Casey et al., 2010; Spear, 2000).
    Amygdalostriatal interactions during development In spite of the fact that the relationship between the amygdala and striatum is critical in maturity, an important outstanding question pertains to the development of the interactions between the amygdala and striatum. Anatomical connectivity between these regions in the rodent is present at adult-like levels early in life, emerging by postnatal day 7 (corresponding roughly to human infancy), with no significant changes after that point (Bouwmeester et al., 2002). Human resting-state fMRI findings support the early emergence and importance of amygdalostriatal interactions across species, reporting the existence of positive functional connectivity between the amygdala and ventral striatum as early as age 4, which remains significantly positive into early adulthood (i.e., early 20s) (Fareri et al., 2015b). However, there has been little characterization of the normative development of task-based amygdalostriatal functional interactions and how they may relate to affective valuation. Prominent dual systems models of human neurobehavioral development point to the relationship between the ventral striatum and prefrontal cortex, suggesting that regulatory abilities relying on prefrontal cortex are not maturely developed and efficient, underlying adolescent sensitivity to reward (reviewed in Crone and Dahl, 2012; Pfeifer and Allen, 2012). Others suggest a three-pronged model of affective behavior consisting of the ventral striatum, amygdala and vmPFC, corresponding to reward, avoidance and control systems, respectively (Ernst et al., 2006), hypothesizing that adolescent behavior is biased towards reward-seeking behavior due to increased influence of the ventral striatum and away from avoidance-based behaviors. Similarly to dual process models, however, this relationship is proposed to be mediated by the protracted development of PFC regulatory function, which together underlies increases in adolescent risk-taking behavior. While influential, recent suggestions have called for more expansive and integrative models of adolescent neurobehavioral development, calling for the incorporation of additional methodological approaches (Pfeifer and Allen, 2012), consideration of the changing importance of social contexts during development (Crone and Dahl, 2012), and more nuanced and complex roles for the amygdala and striatum in affective valuation and learning (Somerville et al., 2014). Imbalance models (Casey, 2015; Casey et al., 2010) further highlight the importance of non-linear changes during the transitions from childhood to adolescence and from adolescence to adulthood. Such models emphasize the importance of hormonal changes in conjunction with circuit-based structural and functional neural changes, which together create an imbalance underlying behavioral development that could have adaptive or maladaptive consequences (Casey, 2015; Casey et al., 2010). A recent example of such efforts suggests that adolescents may interpret threatening stimuli or situations as thrilling or exciting, leading to a tendency to reinterpret avoidance based signals as approachable (Spielberg et al., 2014). According to this hypothesis, the kinase inhibitors amygdala and striatum may in fact work together to promote risk-taking behavior in certain situations, driven in part by developmental changes in pubertal hormone levels (Spielberg et al., 2014) Such interactions may have implications for individual differences in temperament, as behaviorally inhibited individuals show reduced resting state functional connectivity between the amygdala and striatum (Roy et al., 2014), and for the development of internalizing illness as well. Given that the drastic developmental changes in the amygdala and striatum early in life, an intriguing further possibility is that early experiences may shape later ventral striatal function through the amygdala.