The NO-cGMP-PKG signaling pathway regulates synaptic plasticity and fear memory consolidation in the lateral amygdala via activation of ERK/MAP kinase

Recent studies have shown that nitric oxide (NO) signaling plays a crucial role in memory consolidation of Pavlovian fear conditioning and in synaptic plasticity in the lateral amygdala (LA). In the present experiments, we examined the role of the cGMP-dependent protein kinase (PKG), a downstream effector of NO, in fear memory consolidation and long-term potentiation (LTP) at thalamic and cortical input pathways to the LA. In behavioral experiments, rats given intra-LA infusions of either the PKG inhibitor Rp-8-Br-PET-cGMPS or the PKG activator 8-Br-cGMP exhibited dose-dependent impairments or enhancements of fear memory consolidation, respectively. In slice electrophysiology experiments, bath application of Rp-8-Br-PET-cGMPS or the guanylyl cyclase inhibitor LY83583 impaired LTP at thalamic, but not cortical inputs to the LA, while bath application of 8-Br-cGMP or the guanylyl cyclase activator YC-1 resulted in enhanced LTP at thalamic inputs to the LA. Interestingly, YC-1-induced enhancement of LTP in the LA was reversed by concurrent application of the MEK inhibitor U0126, suggesting that the NO-cGMP-PKG signaling pathway may promote synaptic plasticity and fear memory formation in the LA, in part by activating the ERK/MAPK signaling cascade. As a test of this hypothesis, we next showed that rats given intra-LA infusion of the PKG inhibitor Rp-8-Br-PET-cGMPS or the PKG activator 8-Br-cGMP exhibit impaired or enhanced activation, respectively, of ERK/MAPK in the LA after fear conditioning. Collectively, our findings suggest that an NO-cGMP-PKG-dependent form of synaptic plasticity at thalamic input synapses to the LA may underlie memory consolidation of Pavlovian fear conditioning, in part, via activation of the ERK/MAPK signaling cascade.     

The Existential Quantifier, Composition and Contingency

There is a good deal of disagreement about composition. There is first-order disagreement: there are radically different answers to the special composition question—the question of under what circumstances the xs compose a y. There is second-order disagreement: there are different answers to the question of whether first-order disagreement is real or merely semantic. Virtually all disputants with respect to both the first- and second-order issues agree that the answer or answers to the special composition question will take the form of a necessary truth or truths even though, as I will argue, such answers do not appear to be good candidates to be necessary truths. This paper provides an analysis of the concept of <exists> as it pertains to concrete objects, that fulfils two functions. First, it explicates the sense in which claims about composition are contingent and the sense in which they are necessary, and second, it provides a way of understanding when first-order disputes are substantial and when they are merely semantic.     

Conjunction-based Sorites: A Misguided Objection to Degree-Theoretic (Fuzzy) Solutions to Sorites Paradoxes

In 1987, Crispin Wright argued that degree-theoretic (fuzzy) solutions to the Sorites paradox fail because the solutions do not work when the paradox is restated using a conjunctive major premise. I show that Wright is incorrect: degree-theoretic solutions also work when the paradox is stated with a conjunctive major premise.     

Selbstreferenz und Zeit: Die dynamische Stabilität des Bewusstseins

Ohne Zusammenfassung     

The new growing block theory vs presentism

It was once held to be a virtue of the growing block theory that it combines temporal dynamism with a straightforward account of in virtue of what past-tensed propositions are true, and an explanation for why some future-tensed propositions are not true (assuming they are not). This put the growing block theory ahead of its principal dynamist rival: presentism. Recently, new growing block theorists have suggested that what makes true, past-tensed propositions, is not the same kind of thing as what makes true, present-tensed propositions. They have done so in an attempt to defuse a particular epistemic objection to their view. In this paper it is argued that the new growing block theorist faces a dilemma. The more unified a strategy is for responding to the epistemic objection, the more that strategy results in the new growing block model positing truthmakers that are similar to those posited by the presentist, which erodes the purported advantage of the growing block theory over presentism. On the other hand, versions of the new growing block theory that embrace disunified strategies are better able to differentiate themselves from presentism, but are unattractive because of their disunity.     

The Unique Groundability of Temporal Facts

The A‐theory and the B‐theory advance competing claims about how time is grounded. The A‐theory says that A‐facts are more fundamental in grounding time than are B‐facts, and the B‐theory says the reverse. We argue that whichever theory is true of the actual world is also true of all possible worlds containing time. We do this by arguing that time is uniquely groundable: however time is actually grounded, it is necessarily grounded in that way. It follows that if either the A‐theory or the B‐theory is actually false, then it is necessarily false.     

The Efficacy of Child Parent Relationship Therapy for Adoptive Families: A Replication Study

This randomized controlled replication study examined the effectiveness of child parent relationship therapy (CPRT) with 49 adoptive families. Statistically significant improvement and large treatment effects for child behavior problems, parent–child relationship stress, and parents' empathic interactions with their children indicated the effectiveness of CPRT over treatment as usual. Findings confirm Carnes‐Holt and Bratton's ( 2014 ) results and provide strong support for CPRT as a responsive intervention for adoptive families.     

1984: A Love Letter

Dear Kris, I know you will read this letter if it ever manages to get to you. You like reading. I’m not sure what you’ll think of it though. I just know I had to make this attempt to talk to you about the summer of 1984. There are some things you and I come to know in the summer of 1984 that will take us 35 years to learn to talk about. They were not an easy 35 years. And I want to help change that.     

Influence of intake of sweet solutions on the analgesic effect of a low dose of morphine in randomly bred rats

The time course for the development of morphine tolerance, following prolonged sweet intake, was examined in randomly bred Sabra rats. Exposure to 3% glucose in 6 mM saccharin solution increased drinking by about three times as compared to rats supplied only with water. Suppression of the analgesic effect of morphine was already detectable after 24 h of intake and became progressively more marked within the next 5 weeks. These results support an active interaction between sweet consumption and endogenous opioids in randomly bred rats.     

Freud's three theories of love in the light of later developments

Evidence is presented that Freud developed three very different theories on love. These theories were not integrated into a coherent theory. In subsequent developments each theory had its own history. The paper discusses the history of the controversy on the genital character, the relation between love and gender identity, between love and narcissism, the hierarchical structure of the capacity to love, and the relation between love and object loss. The impact of some concepts such as symbiosis and the rapprochmente subphase on the understanding of conflicts in loving is raised. While at present differences in emphasis make it difficult to build a coherent psychoanalytic theory of love, it is productive to bring divergent views in touch with each other. A unified theory of love based on psychoanalytic observations is suggested.