Tianeptine induces expression of dual specificity phosphatases and evokes rebound emergence of cortical slow wave electrophysiological activity

Funding Information: This work was supported by the Academy of Finland (grant numbers 276333 , 305195 , 312664 , 322906 ) and the Finnish Pharmaceutical Society . Funding Information: This work was supported by the Academy of Finland (grant numbers 276333, 305195, 312664, 322906) and the Finnish Pharmaceutical Society. T.R. is listed as a co-inventor on a patent application wherein new EEG monitoring tools potentially enabling the development of rapid-acting antidepressants and the efficacy monitors thereof are disclosed. T.R. has assigned his patent rights to the University of Helsinki but will share a percentage of any royalties that may be received by the University of Helsinki. Publisher Copyright: © 2021 The AuthorsBackground: The precise mechanism governing the antidepressant effects of tianeptine is unknown. Modulation of brain glutamatergic neurotransmission has been however implicated, suggesting potential shared features with rapid-acting antidepressants targeting N-methyl-D-aspartate receptors (NMDAR). Our recent studies suggest that a single subanesthetic dose of NMDAR antagonists ketamine or nitrous oxide (N2O) gradually evoke 1–4 Hz electrophysiological activity (delta-rhythm) of cerebral cortex that is accompanied by molecular signaling associated with synaptic plasticity (e.g. activation of tropomyosin receptor kinase B (TrkB) and inhibition of glycogen synthase kinase 3β (GSK3β)). Methods: We have here investigated the time-dependent effects of tianeptine (30 mg/kg, i.p.) on electrocorticogram, focusing on potential biphasic regulation of the delta-rhythm. Selected molecular markers associated with ketamine's antidepressant effects were analyzed in the medial prefrontal cortex after the treatment using quantitative polymerase chain reaction and western blotting. Results: An acute tianeptine treatment induced changes of electrocorticogram typical for active wakefulness that lasted for 2–2.5 h, which was followed by high amplitude delta-activity rebound. The levels of Arc and Homer1a, but not c-Fos, BdnfIV and Zif268, were increased by tianeptine. Phosphorylation of mitogen-activated protein kinase (MAPK), TrkB and GSK3β remained unaltered at 2-hours and at 3-hours post-treatment. Notably, tianeptine also increased the level of mRNA of several dual specificity phosphatases (Duspss) – negative regulators of MAPK. Conclusion: Tianeptine produces acute changes of electrocorticogram resembling rapid-acting antidepressants ketamine and N2O. Concomitant regulation of Dusps may hamper the effects of tianeptine on MAPK pathway and influence the magnitude of homeostatic emergence of delta-activity and TrkB-GSK3β signaling.Peer reviewe

Ludics and its Applications to natural Language Semantics

Proofs, in Ludics, have an interpretation provided by their counter-proofs, that is the objects they interact with. We follow the same idea by proposing that sentence meanings are given by the counter-meanings they are opposed to in a dialectical interaction. The conception is at the intersection of a proof-theoretic and a game-theoretic accounts of semantics, but it enlarges them by allowing to deal with possibly infinite processes

Community of inquiry and inquiry-based learning

Peer reviewe

Rich Situated Attitudes

We outline a novel theory of natural language meaning, Rich Situated Semantics [RSS], on which the content of sentential utterances is semantically rich and informationally situated. In virtue of its situatedness, an utterance’s rich situated content varies with the informational situation of the cognitive agent interpreting the utterance. In virtue of its richness, this content contains information beyond the utterance’s lexically encoded information. The agent-dependence of rich situated content solves a number of problems in semantics and the philosophy of language (cf. [14, 20, 25]). In particular, since RSS varies the granularity of utterance contents with the interpreting agent’s informational situation, it solves the problem of finding suitably fine- or coarse-grained objects for the content of propositional attitudes. In virtue of this variation, a layman will reason with more propositions than an expert

The ecological importance of habitat complexity to the Caribbean coral reef herbivore <i>Diadema antillarum</i>: three lines of evidence

When Caribbean long-spined sea urchins, Diadema antillarum, are stable at high population densities, their grazing facilitates scleractinian coral dominance. Today, populations remain suppressed after a mass mortality in 1983–1984 caused a loss of their ecosystem functions, and led to widespread declines in ecosystem health. This study provides three lines of evidence to support the assertion that a lack of habitat complexity on Caribbean coral reefs contributes to their recovery failure. Firstly, we extracted fractal dimension (D) measurements, used as a proxy for habitat complexity, from 3D models to demonstrate that urchins preferentially inhabit areas of above average complexity at ecologically relevant spatial scales. Secondly, controlled behaviour experiments showed that an energetically expensive predator avoidance behaviour is reduced by 52% in complex habitats, potentially enabling increased resource allocation to reproduction. Thirdly, we deployed a network of simple and cost-effective artificial structures on a heavily degraded reef system in Honduras. Over a 24-month period the adult D. antillarum population around the artificial reefs increased by 320% from 0.05 ± 0.01 to 0.21 ± 0.04 m−2 and the juvenile D. antillarum population increased by 750% from 0.08 ± 0.02 to 0.68 ± 0.07 m−2. This study emphasises the important role of habitat structure in the ecology of D. antillarum and as a barrier to its widespread recovery

Efficiency Theory: a Unifying Theory for Information, Computation and Intelligence

The paper serves as the first contribution towards the development of the theory of efficiency: a unifying framework for the currently disjoint theories of information, complexity, communication and computation. Realizing the defining nature of the brute force approach in the fundamental concepts in all of the above mentioned fields, the paper suggests using efficiency or improvement over the brute force algorithm as a common unifying factor necessary for the creation of a unified theory of information manipulation. By defining such diverse terms as randomness, knowledge, intelligence and computability in terms of a common denominator we are able to bring together contributions from Shannon, Levin, Kolmogorov, Solomonoff, Chaitin, Yao and many others under a common umbrella of the efficiency theory

Changing a semantics: opportunism or courage?

The generalized models for higher-order logics introduced by Leon Henkin, and their multiple offspring over the years, have become a standard tool in many areas of logic. Even so, discussion has persisted about their technical status, and perhaps even their conceptual legitimacy. This paper gives a systematic view of generalized model techniques, discusses what they mean in mathematical and philosophical terms, and presents a few technical themes and results about their role in algebraic representation, calibrating provability, lowering complexity, understanding fixed-point logics, and achieving set-theoretic absoluteness. We also show how thinking about Henkin's approach to semantics of logical systems in this generality can yield new results, dispelling the impression of adhocness. This paper is dedicated to Leon Henkin, a deep logician who has changed the way we all work, while also being an always open, modest, and encouraging colleague and friend.Comment: 27 pages. To appear in: The life and work of Leon Henkin: Essays on his contributions (Studies in Universal Logic) eds: Manzano, M., Sain, I. and Alonso, E., 201

The coinductive formulation of common knowledge

We study the coinductive formulation of common knowledge in type theory. We formalise both the traditional relational semantics and an operator semantics, similar in form to the epistemic system S5, but at the level of events on possible worlds rather than as a logical derivation system. We have two major new results. Firstly, the operator semantics is equivalent to the relational semantics: we discovered that this requires a new hypothesis of semantic entailment on operators, not known in previous literature. Secondly, the coinductive version of common knowledge is equivalent to the traditional transitive closure on the relational interpretation. All results are formalised in the proof assistants Agda and Coq