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Differences in motor learning can be partially explained by differences in genotype. The catechol-O-methyltransferase (COMT) Val158Met polymorphism regulates the dopamine (DA) availability in the prefrontal cortex modulating motor learning and performance. Given the differences in tonic and phasic DA transmission, this study aimed to investigate whether the greater cognitive flexibility associated with the Val allele would favor the learning of movement parametrization, while the greater cognitive stability associated with the Met allele favors the acquisition of the movement pattern. Furthermore, we investigated if the genotypic characteristics impact visual scanning of information related to parametrization and to the movement pattern, and the level of cortical connectivity associated with motor planning and control. Performance and learning of a sequential motor task were compared among three genotypes (Val/Val, Val/Met, and Met/Met), as well as their oculomotor behavior and level of cortical coherence. The findings show that the cognitive flexibility promoted by the Val allele is associated with a better parametrization. The search for information through visual scanning was specific to each genotype. Also, a greater cortical connectivity associated with the Val allele was found. The combined study of behavioral, electrophysiological and molecular levels of analysis showed that the cognitive stability and flexibility associated with the COMT alleles, influence specific aspects of motor learning., Competing Interests: Declaration of Competing Interest There are no conflicts of interest., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Ubiquitination is involved in synaptic plasticity and memory, but the involvement of HECT E3 ligases in these processes has not yet been established. Here, we bilaterally infused heclin, a specific inhibitor of some of these ligases, into the dorsal hippocampus of male Wistar rats that were trained in a contextual fear conditioning. Heclin improved short-term memory, consolidation, retrieval, and reconsolidation when administered immediately post training, prior to testing, or after memory reactivation, respectively. In addition, it impaired memory extinction when administered prior to a long reactivation session. Heclin infusion was also tested for locomotor activity and anxiety-like behavior in a circular arena, but no effect was seen. Taken together, these results indicate that HECT E3 ligases are involved in the modulation of fear memory., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Rats were implanted with cannulae in the CA1 area of the dorsal hippocampus or in the entorhinal cortex and trained in one-trial step-down inhibitory avoidance. Two retention tests were carried out in each animal, one at 1.5 h to measure short-term memory (STM) and another at 24 h to measure long-term memory (LTM). The purpose of the present study was to screen the effect on STM of various drugs previously shown to affect LTM of this task when given posttraining at the same doses that were used here. The drugs and doses were the guanylyl cyclase inhibitor LY83583 (LY, 2.5 microMg), the inhibitor of Tyr-protein kinase at low concentrations and of protein kinase G (PKG) at higher concentrations lavendustin A (LAV, 0.1 and 0.5 microMg), the PKG inhibitor KT5823 (2.0 microMg), the protein kinase C (PKC) inhibitor staurosporin (STAU, 2.5 microMg), the inhibitor of calcium/ calmodulin protein kinase II (CaMKII) KN62 (3.6 microMg), the protein kinase A (PKA) inhibitor KT5720 (0.5 microMg), and the mitogen-activated protein kinase kinase (MAPKK) inhibitor PD098059 (PD, 0.05 microMg). PD was dissolved in saline; all the other drugs were dissolved in 20% dimethyl sulfoxide. In all cases the drugs affected LTM as had been described in previous papers. The drugs affected STM and LTM differentially depending on the brain structure into which they were infused. STM was inhibited by KT5720, LY, and PD given into CA1 and by STAU and KT5720 given into the entorhinal cortex. PD given into the entorhinal cortex enhanced STM. LTM was inhibited by STAU, KN62, KT5720, KT5823, and LAV (0.5 microMg) given into CA1 and by STAU, KT5720, and PD given into the entorhinal cortex. The results suggest that STM and LTM involve different physiological mechanisms but are to an extent linked. STM appears to require PKA, guanylyl cyclase, and MAPKK activity in CA1 and PKA and PKC activity in the entorhinal cortex; MAPKK seems to play an inhibitory role in STM in the entorhinal cortex. In contrast, LTM appears to require PKA and PKC activity in both structures, guanylyl cyclase, PKG, and CaMKII activity in CA1, and MAPKK activity in the entorhinal cortex., (Copyright 2000 Academic Press.)

Rats with cannulae implanted in the junction between the central and the basolateral nuclei of the amygdala were trained in one-trial step-down inhibitory avoidance and tested at 3 s for working memory (WM) or 1.5 or 24 h later for short-term memory (STM) and long-term memory (LTM), respectively. Several drugs were infused 6 min prior to training in the animals in which WM was measured or 0 min posttraining in those in which STM and LTM were measured: the glutamate receptor antagonists CNQX (0.5 microg) and AP5 (5.0 microg), the indirect GABA A receptor antagonist picrotoxin (0.08 microg), the cholinergic muscarinic receptor blocker scopolamine (2. 0 microg), norepinephrine (0.3 microg), the protein kinase C inhibitor staurosporin (1.0 microg), or the calcium/calmodulin dependent protein kinase II inhibitor Kn-62 (3.5 ng). None of the drugs had any effect on either WM or STM. All had, as previously shown, strong effects on LTM: picrotoxin and norepinephrine enhanced it, and CNQX, AP5, scopolamine, Kn-62, and staurosporin inhibited it. The results do not support the idea that memory of this task is formed in the amygdala; they indicate that the amygdala is not involved in WM or STM processing and support the idea that the amygdala modulates LTM storage processes carried out elsewhere., (Copyright 1999 Academic Press.)

Rats with cannulae implanted in the dorsal CA1 region of the hippocampus or in the entorhinal cortex (EC) were trained in one-trial step-down inhibitory avoidance and tested 1.5 or 24 h later, in order to measure short-term memory (STM) and long-term memory (LTM) respectively. Several drugs infused immediately post-training inhibited STM without altering LTM: the D1 receptor agonist SKF38393 (7.5 microgram) given into either CA1 or EC, the beta blocker timolol (0.3 microgram) given into EC, the 5HT1A receptor agonist 8-HO-DPAT (2.5 microgram) given into CA1, and the 5HT1A antagonist NAN-190 (2.5 microgram) given into EC. These findings indicate that STM is not a necessary step toward LTM. Intraentorhinal 8-HO-DPAT enhanced STM and depressed LTM. The D1 antagonist SCH23390 (0.5 microgram) enhanced STM without affecting LTM when given into CA1, and blocked LTM without affecting STM when given into EC. Intraentorhinal norepinephrine (0.3 microgram) enhanced both STM and LTM, and the same drug when given into CA1 enhanced LTM selectively. None of the drugs had any effect on retrieval of either STM or LTM when given prior to testing. The data indicate that STM and LTM are differentially modulated by D1, beta, and 5HT1A receptors in CA1 and EC., (Copyright 1998 Academic Press.)