The rat frontal orienting field dynamically encodes value for economic decisions under risk.

Frontal and parietal cortex are implicated in economic decision-making, but their causal roles are untested. Here we silenced the frontal orienting field (FOF) and posterior parietal cortex (PPC) while rats chose between a cued lottery and a small stable surebet. PPC inactivations produced minimal short-lived effects.

Negative transfer effects between reference memory and working memory training in the water maze in C57BL/6 mice.

The water maze is one of the most widely employed spatial learning paradigms in the cognitive profiling of genetically modified mice. Oftentimes, tests of reference memory (RM) and working memory (WM) in the water maze are sequentially evaluated in the same animals. However, critical difference in the rules governing efficient escape from the water between WM and RM tests is expected to promote the adoption of incompatible mnemonic or navigational strategies.

Inhibition of glycine transporter 1: The yellow brick road to new schizophrenia therapy?

While pharmacological blockade of dopamine D2 receptor can effectively suppress the psychotic or positive symptoms of schizophrenia, there is no satisfactory medication for the negative and cognitive symptoms of schizophrenia in spite of the proliferation of second generation antipsychotic drugs. Excitements over a new class of third generation antipsychotics that might possibly fill this urgent medical need have been prompted by the recent development of glycine transporter 1 (GlyT1) inhibitors. The impetus of this novel pharmacological strategy stems directly from the prevailing hypothesis that negative and cognitive symptoms are attributable to the hypofunction of glutamatergic signalling via the N-methyl-D-aspartate (NMDA) receptor in the brain.

Radixin regulates synaptic GABAA receptor density and is essential for reversal learning and short-term memory.

Neurotransmitter receptor density is a major variable in regulating synaptic strength. Receptors rapidly exchange between synapses and intracellular storage pools through endocytic recycling. In addition, lateral diffusion and confinement exchanges surface membrane receptors between synaptic and extrasynaptic sites.

Caffeine impairs the acquisition and retention, but not the consolidation of Pavlovian conditioned freezing in mice.

Rationale: The psychoactive substance, caffeine, may improve cognitive performance, but its direct impact on learning and memory remains ill defined. Conflicting reports suggest that caffeine may impair as well as enhance Pavlovian fear conditioning in animals and its effect may vary across different phases of learning.

Objectives: The purpose of this study is to dissect the effect of a motor-stimulant dose of caffeine (30 mg/kg intraperitoneal (i.

Deletion of forebrain glycine transporter 1 enhances conditioned freezing to a reliable, but not an ambiguous, cue for threat in a conditioned freezing paradigm.

Enhanced expression of Pavlovian aversive conditioning but not appetitive conditioning may indicate a bias in the processing of threatening or fearful events. Mice with disruption of glycine transporter 1 (GlyT1) in forebrain neurons exhibit such a bias, but they are at the same time highly sensitive to manipulations that hinder the development of the conditioned response (CR) suggesting that the mutation may modify higher cognitive processes that extract predictive information between environmental cues. Here, we further investigated the development of fear conditioning in forebrain neuronal GlyT1 knockout mice when the predictiveness of a tone stimulus for foot-shock was rendered ambiguous by interspersing [tone→no shock] trials in-between [tone→shock] trials during acquisition.

Sensorimotor gating is disrupted by acute but not chronic systemic exposure to caffeine in mice.

Rationale: Caffeine is a psychostimulant drug that blocks adenosine A₁ and A₂A receptors (A₁Rs and A₂ARs). However, its ability to disrupt early sensory gating as indexed by prepulse inhibition (PPI), which is consistently disrupted by other psychostimulant agents, has never been convincingly demonstrated.

Objectives: To compare the impact of caffeine on PPI expression in C57BL/6 mice by two dose-response experiments differing in terms of chronicity, regimen, and route of administration.

Forebrain glycine transporter 1 deletion enhances sensitivity to CS-US discontiguity in classical conditioning.

The deletion of glycine transporter 1 (GlyT1) in forebrain neurons can apparently strengthen Pavlovian aversive conditioning, but this phenotype is not expressed if conditioning followed non-reinforced pre-exposures of the to-be-conditioned stimulus (CS). To examine whether GlyT1 disruption may only enhance aversive associative learning under conditions that most favour the formation of CS-US excitatory link, we evaluated the impact of GlyT1 disruption on the trace conditioning procedure whereby a trace interval between a tone CS and a shock US was introduced during conditioning. CS and US occurrences were thus rendered discontiguous, which was expected to impede conditioning compared with contiguous CS-US pairing.

Intact working memory in the absence of forebrain neuronal glycine transporter 1.

Glycine transporter 1 (GlyT1) is a potential pharmacological target to ameliorate memory deficits attributable to N-methyl-d-aspartate receptor (NMDAR) hypofunction. Disruption of glycine-reuptake near excitatory synapses is expected to enhance NMDAR function by increasing glycine-B site occupancy. Genetic models with conditional GlyT1 deletion restricted to forebrain neurons have yielded several promising promnesic effects, yet its impact on working memory function remains essentially unanswered because the previous attempt had yielded un-interpretable outcomes.

Examining the sex- and circadian dependency of a learning phenotype in mice with glycine transporter 1 deletion in two Pavlovian conditioning paradigms.

Behavioural characterisation of transgenic mice has been instrumental in search of therapeutic targets for the modulation of cognitive function. However, little effort has been devoted to phenotypic characterisation across environmental conditions and genomic differences such as sex and strain, which is essential to translational research. The present study is an effort in this direction.

Impacts of forebrain neuronal glycine transporter 1 disruption in the senescent brain: evidence for age-dependent phenotypes in Pavlovian learning.

Genetic deletion of glycine transporter 1 (GlyT1) in forebrain neurons gives rise to multiple-procognitive phenotypes, presumably due to enhanced N-methyl-d-aspartate receptor (NMDAR) functions. However, concerns over possible harmful excitotoxic effects under lifelong elevation of synaptic glycine have been raised. Such effects might accelerate the aging process, weakening or even reversing the procognitive phenotypes identified in adulthood.

Sensorimotor gating and vigilance-dependent choice accuracy: a within-subject correlative analysis in wild-type C57BL/6 mice.

Deterioration in attention and related processes is an early sign in schizophrenia predictive of disease development. Amongst the various translational paradigms for assessing attention in rodents, it is not known if they are equivalent in detecting individual differences. Answers here are pertinent to their use in the general human population for identifying individuals at high risk of developing schizophrenia.