Synaptic tagging and capture : differential role of distinct calcium/calmodulin kinases in protein synthesis-dependent long-term potentiation

Weakly tetanized synapses in area CA1 of the hippocampus that ordinarily display long-term potentiation lasting ~3 h (called early-LTP) will maintain a longer-lasting change in efficacy (late-LTP) if the weak tetanization occurs shortly before or after strong tetanization of an independent, but convergent, set of synapses in CA1. The synaptic tagging and capture hypothesis explains this heterosynaptic influence on persistence in terms of a distinction between local mechanisms of synaptic tagging and cell-wide mechanisms responsible for the synthesis, distribution, and capture of plasticity-related proteins (PRPs). We now present evidence that distinct CaM kinase (CaMK) pathways serve a dissociable role in these mechanisms. Using a hippocampal brain-slice preparation that permits stable long-term recordings in vitro for >10 h and using hippocampal cultures to validate the differential drug effects on distinct CaMK pathways, we show that tag setting is blocked by the CaMK inhibitor KN-93 (2-[N-(2-hydroxyethyl)]-N-(4-methoxybenzenesulfonyl)amino-N-(4-chlorocinnamyl)-N-methylbenzylamine) that, at low concentration, is more selective for CaMKII. In contrast, the CaMK kinase inhibitor STO-609 [7H-benzimidazo(2,1-a)benz(de)isoquinoline-7-one-3-carboxylic acid] specifically limits the synthesis and/or availability of PRPs. Analytically powerful three-pathway protocols using sequential strong and weak tetanization in varying orders and test stimulation over long periods of time after LTP induction enable a pharmacological dissociation of these distinct roles of the CaMK pathways in late-LTP and so provide a novel framework for the molecular mechanisms by which synaptic potentiation, and possibly memories, become stabilized

Polynomial Path Orders: A Maximal Model

This paper is concerned with the automated complexity analysis of term rewrite systems (TRSs for short) and the ramification of these in implicit computational complexity theory (ICC for short). We introduce a novel path order with multiset status, the polynomial path order POP*. Essentially relying on the principle of predicative recursion as proposed by Bellantoni and Cook, its distinct feature is the tight control of resources on compatible TRSs: The (innermost) runtime complexity of compatible TRSs is polynomially bounded. We have implemented the technique, as underpinned by our experimental evidence our approach to the automated runtime complexity analysis is not only feasible, but compared to existing methods incredibly fast. As an application in the context of ICC we provide an order-theoretic characterisation of the polytime computable functions. To be precise, the polytime computable functions are exactly the functions computable by an orthogonal constructor TRS compatible with POP*

Proof Theory and Ordered Groups

Ordering theorems, characterizing when partial orders of a group extend to total orders, are used to generate hypersequent calculi for varieties of lattice-ordered groups (l-groups). These calculi are then used to provide new proofs of theorems arising in the theory of ordered groups. More precisely: an analytic calculus for abelian l-groups is generated using an ordering theorem for abelian groups; a calculus is generated for l-groups and new decidability proofs are obtained for the equational theory of this variety and extending finite subsets of free groups to right orders; and a calculus for representable l-groups is generated and a new proof is obtained that free groups are orderable

Polynomial Path Orders

This paper is concerned with the complexity analysis of constructor term rewrite systems and its ramification in implicit computational complexity. We introduce a path order with multiset status, the polynomial path order POP*, that is applicable in two related, but distinct contexts. On the one hand POP* induces polynomial innermost runtime complexity and hence may serve as a syntactic, and fully automatable, method to analyse the innermost runtime complexity of term rewrite systems. On the other hand POP* provides an order-theoretic characterisation of the polytime computable functions: the polytime computable functions are exactly the functions computable by an orthogonal constructor TRS compatible with POP*.Comment: LMCS version. This article supersedes arXiv:1209.379