Central blockade of oxytocin receptors during mid-late gestation reduces amplitude of slow afterhyperpolarization in supraoptic oxytocin neurons

The neurohypophysial hormone oxytocin (OT), synthesized in magnocellular paraventricular (PVN) and supraoptic (SON) nuclei, is well known for its effects in lactation. Our previous studies showed that central OT receptor (OTR) binding is increased during gestation and that blockade of central OTRs, specifically during mid-late gestation, causes a delay in OT release during suckling and reduces weight gain in pups, suggesting decreased milk delivery. In the present study, we tested whether central OTR blockade during late gestation disrupts the gestation-related plasticity in intrinsic membrane properties. Whole cell current-clamp recordings were performed in OT neurons from pregnant rats (19-22 days in gestation) that were infused with an OTR antagonist (OTA) or artificial cerebrospinal fluid (aCSF) and from virgin rats infused with aCSF into the third ventricle via an osmotic minipump beginning on days 12-14 of gestation. The amplitudes of both Ca2+-dependent afterhyperpolarizations (AHPs), an apamin-sensitive medium AHP (mAHP) and an apamin-insensitive slow AHP (sAHP), were significantly increased during late gestation in control pregnant animals. However, the amplitude of the sAHP from pregnant rats treated with the OTA was significantly smaller than that of pregnant control rats and similar to that of virgins. These results indicate that the diminished efficiency in lactation due to OTR blockade may be partly a result of an altered sAHP that would shape OT bursting. These findings suggest that central actions of OT during late gestation are necessary for programming the plasticity of at least some of the intrinsic membrane properties in OT neurons during lactation. Copyright © 2008 the American Physiological Society

Can Modal Skepticism Defeat Humean Skepticism?

My topic is moderate modal skepticism in the spirit of Peter van Inwagen. Here understood, this is a conservative version of modal empiricism that severely limits the extent to which an ordinary agent can reasonably believe “exotic” possibility claims. I offer a novel argument in support of this brand of skepticism: modal skepticism grounds an attractive (and novel) reply to Humean skepticism. Thus, I propose that modal skepticism be accepted on the basis of its theoretical utility as a tool for dissolving philosophical paradox

The bearable lightness of being

How are philosophical questions about what kinds of things there are to be understood and how are they to be answered? This paper defends broadly Fregean answers to these questions. Ontological categories-such as object, property, and relation-are explained in terms of a prior logical categorization of expressions, as singular terms, predicates of varying degree and level, etc. Questions about what kinds of object, property, etc., there are are, on this approach, reduce to questions about truth and logical form: for example, the question whether there are numbers is the question whether there are true atomic statements in which expressions function as singular terms which, if they have reference at all, stand for numbers, and the question whether there are properties of a given type is a question about whether there are meaningful predicates of an appropriate degree and level. This approach is defended against the objection that it must be wrong because makes what there depend on us or our language. Some problems confronting the Fregean approach-including Frege's notorious paradox of the concept horse-are addressed. It is argued that the approach results in a modest and sober deflationary understanding of ontological commitments

"Phenomenal Conservatism" - Ch 2 of Seemings and Epistemic Justification

In this chapter I introduce and analyse the tenets of phenomenal conservatism, and discuss the problem of the nature of appearances. After that, I review the asserted epistemic merits phenomenal conservatism and the principal arguments adduced in support of it. Finally, I survey objections to phenomenal conservatism and responses by its advocates. Some of these objections will be scrutinised and appraised in the next chapters

Unity through truth

Renewed worries about the unity of the proposition have been taken as a crucial stumbling block for any traditional conception of propositions. These worries are often framed in terms of how entities independent of mind and language can have truth conditions: why is the proposition that Desdemona loves Cassio true if and only if she loves him? I argue that the best understanding of these worries shows that they should be solved by our theory of truth and not our theory of content. Specifically, I propose a version of the redundancy theory according to which ‘it is true that Desdemona loves Cassio’ expresses the same proposition as ‘Desdemona loves Cassio’. Surprisingly, this variant of the redundancy theory treats ‘is true’ as an ordinary predicate of the language, thereby defusing many standard criticisms of the redundancy theory