A More Unified Approach to Free Logics

Journal of Philosophical Logic - Free logics is a family of first-order logics which came about as a result of examining the existence assumptions of classical logic. What those assumptions are...     

Learning in the absence of experience-dependent regulation of NMDAR composition

Olfactory discrimination (OD) learning consists of two phases: an initial N-methyl-D-aspartate (NMDA) receptor-sensitive rule-learning phase, followed by an NMDA receptor (NMDAR)-insensitive pair-learning phase. The rule-learning phase is accompanied by changes in the composition and function of NMDARs at synapses in the piriform cortex, resulting in a high level of the NR2a subunit relative to NR2b. Here we show that the learning-induced changes in NMDAR composition in the adult piriform cortex are due to a decrease in the level of the NR2b subunit protein, rather than an increase in the level of NR2a. Chronic administration of an NMDAR open channel blocker during training delays OD learning and blocks learning-induced changes in NMDAR subunit composition. However, the animals still learn the OD task. Our data demonstrate that learning can occur in the absence of activity-dependent regulation of NMDAR composition, suggesting differences in the mechanism for long-term maintenance of NMDAR-dependent and NMDAR-independent learning.     

Olfactory learning-induced enhancement of the predisposition for LTP induction

Learning of a particularly difficult olfactory-discrimination (OD) task results in acquisition of rule learning. This enhancement in learning capability is accompanied by the long-term enhancement of synaptic connectivity between piriform cortex pyramidal neurons. In this study we examined whether olfactory rule learning would modify the predisposition to induce long-term potentiation (LTP) in the pathway projecting from the piriform cortex to the olfactory bulb. We report that OD learning was associated with enhancement in the predisposition to induce LTP. This learning-related effect may be affected by process generation of new granule cells located in the olfactory bulb.     

Persistent ERK activation maintains learning-induced long-lasting modulation of synaptic connectivity

Pyramidal neurons in the piriform cortex from olfactory-discrimination (OD) trained rats undergo synaptic modifications that last for days after learning. A particularly intriguing modification is reduced paired-pulse facilitation (PPF) in the synapses interconnecting these cells; a phenomenon thought to reflect enhanced synaptic release. The molecular machinery underlying this prolonged physiological modulation of synaptic connectivity is yet to be described. We have recently shown that extracellular regulated kinase (ERK) pathway and protein kinase C (PKC) are also required for learning-induced enhancement of intrinsic neuronal excitability. Here we examine whether these signal-transduction cascades are instrumental for the learning-induced, long-lasting PPF reduction. Days after learning completion, PD98059, a selective inhibitor of MEK, the upstream kinase of ERK, increased PPF in neurons from trained, but not in neurons from na?ve and pseudo-trained rats. Consequently, the differences in PPF between neurons from trained rats and controls were abolished. The level of activated ERK in synaptoneurosomes was significantly higher in piriform cortex samples prepared from trained rats. Notably, ERK activation revealed that PPF reduction lags behind ERK activation by 2 d. Similarly, the PKC blocker, GF-109203X, enhanced PPF in neurons from trained rats only, thus abolishing the differences between groups. Interestingly, the PKC activator, OAG, had no effect, indicating that PKC activation is required, but not sufficient for long-lasting PPF reduction. Our data show that persistent ERK activation has a key role in maintaining learning-induced PPF reduction for days. This time frame of compartmental ERK-dependent synaptic modulation suggests a novel role for ERK in cortical function.