A reinforcement schedule with two types of temporal information.

Decades of research on reinforcement schedules have demonstrated that temporal information regarding the arrival or nonarrival of biologically significant events controls animal behavior. The fixed interval (FI) schedule, which is a time-based reinforcement schedule, suggests that responses are regulated by the time elapsed since the last reinforcement. This raises the question of how behavior is controlled when two distinct temporal cues regarding the availability of reinforcers are simultaneously presented.

Chemogenetic activation of mammalian brain neurons expressing insect Ionotropic Receptors by systemic ligand precursor administration.

Chemogenetic approaches employing ligand-gated ion channels are advantageous regarding manipulation of target neuronal population functions independently of endogenous second messenger pathways. Among them, Ionotropic Receptor (IR)-mediated neuronal activation (IRNA) allows stimulation of mammalian neurons that heterologously express members of the insect chemosensory IR repertoire in response to their cognate ligands. In the original protocol, phenylacetic acid, a ligand of the IR84a/IR8a complex, was locally injected into a brain region due to its low permeability of the blood-brain barrier.

Catecholaminergic cell type-specific expression of Cre recombinase in knock-in transgenic rats generated by the Combi-CRISPR technology.

Background: Cell groups containing catecholamines provide a useful model to study the molecular and cellular mechanisms underlying the morphogenesis, physiology, and pathology of the central nervous system. For this purpose, it is necessary to establish a system to induce catecholaminergic group-specific expression of Cre recombinase. Recently, we introduced a gene cassette encoding 2A peptide fused to Cre recombinase into the site between the C-terminus and translational termination codons of the rat tyrosine hydroxylase (TH) open reading frame by the Combi-CRISPR technology, which is a genomic editing method to enable an efficient knock-in (KI) of long DNA sequence into a target site.

Multimodal Functional Analysis Platform: 1. Ultrathin Fluorescence Endoscope Imaging System Enables Flexible Functional Brain Imaging.

To elucidate the expression mechanisms of brain functions, we have developed an ultrathin fluorescence endoscope imaging system (U-FEIS) that can image cells in the brain at any depth while minimizing the invasion. The endoscope part of U-FEIS consists of a GRIN lens and a 10,000-pixel image fiber with a diameter of 450 μm. The specialized microscope of U-FEIS is within 30 cm square and includes lenses and optical filters optimized for the endoscope.

Enhanced Retrieval of Taste Associative Memory by Chemogenetic Activation of Locus Coeruleus Norepinephrine Neurons.

The ability of animals to retrieve memories stored in response to the environment is essential for behavioral adaptation. Norepinephrine (NE)-containing neurons in the brain play a key role in the modulation of synaptic plasticity underlying various processes of memory formation. However, the role of the central NE system in memory retrieval remains unclear.

Maternal dietary imbalance between omega-6 and omega-3 fatty acids triggers the offspring's overeating in mice.

The increasing prevalence of obesity and its effects on our society warrant intensifying basic animal research for understanding why habitual intake of highly palatable foods has increased due to recent global environmental changes. Here, we report that pregnant mice that consume a diet high in omega-6 (n-6) polyunsaturated fatty acids (PUFAs) and low in omega-3 (n-3) PUFAs (an n-6/n-3 diet), whose n-6/n-3 ratio is approximately 120, induces hedonic consumption in the offspring by upregulating the midbrain dopaminergic system. We found that exposure to the n-6/n-3 diet specifically increases the consumption of palatable foods via increased mesolimbic dopamine release.

Ethological and multi-behavioral analysis of learning and memory performance in laboratory rodent models.

Behavioral studies using animal models have widely contributed to advancing our understanding of the neuroregulatory mechanisms of human cognitive states and disorders. A variety of behavioral tests and theoretical models have been developed that provide a standardized toolbox of behavioral test paradigms available to researchers, and thus allow rapid progress in studies of the molecular-genetic bases of behavior relevant to neurocognitive diseases. However, a growing effort to utilize standardized paradigms has overlooked the diverse behavioral characteristics of test rodents expressed in standardized test situations.

Identification of an unconventional process of instrumental learning characteristically initiated with outcome devaluation-insensitivity and generalized action selection.

The distinction between goal-directed action and habitual response, particularly with respect to moderate or extended appetitive instrumental training, is well documented; however, the propensity toward instrumental behavior in the early training stage has not been elucidated. In this study, we trained Sprague Dawley rats to press a lever to obtain food as an outcome for various time periods and monitored the changes in their sensitivity to outcome devaluation and choice between the levers they had been trained with and unfamiliar levers. After the extensive training with a random interval schedule, the rats were insensitive to outcome devaluation, and exhibited a typical habit-like phenotype, as previously reported, and the untrained leverpresses were relatively rare and sporadic.

Pre-stress performance in an instrumental training predicts post-stress behavioral alterations in chronically stressed rats.

Stress is a major factor in the development of major depressive disorder (MDD), but few studies have assessed individual risk based on pre-stress behavioral and cognitive traits. To address this issue, we employed appetitive instrumental lever pressing with a progressive ratio (PR) schedule to assess these traits in experimentally naïve Sprague-Dawley rats. Based on four distinct traits that were identified by hierarchical cluster analysis, the animals were classified into the corresponding four subgroups (Low Motivation, Quick Learner, Slow Learner, and Hypermotivation), and exposed to chronic unpredictable stress (CUS) before monitoring their post-stress responses for 4 weeks.

Repeated exposure of adult rats to transient oxidative stress induces various long-lasting alterations in cognitive and behavioral functions.

Exposure of neonates to oxidative stress may increase the risk of psychiatric disorders such as schizophrenia in adulthood. However, the effects of moderate oxidative stress on the adult brain are not completely understood. To address this issue, we systemically administrated 2-cyclohexen-1-one (CHX) to adult rats to transiently reduce glutathione levels.

Effects of extended context discrimination training and context extinction on transfer of context dependency of conditioned flavor aversion.

We trained rats in a context discrimination paradigm by pairing a sucrose solution with lithium chloride in one context (conditioning context) and simple exposure to the same fluid in a second (neutral) context to establish a context-dependent aversion to the conditioned fluid. We then investigated whether transfer of the context dependency to a test fluid (a sodium chloride solution) was affected by two post-discrimination training treatments, an extended context discrimination training, and non-reinforced exposure to the conditioning context (context extinction). We found that the context-dependent flavor aversion that had been specific to sucrose transferred to the test fluid after the extensive training (Experiment 1).

Instrumental outcome devaluation with representation-mediated conditioning.

In three experiments, rats were trained to perform two instrumental behaviours (R1 and R2) in the presence of discriminative stimuli (Sd1 and Sd2, respectively) to obtain a common food outcome (O1). Acquisition of the two discriminations was followed by switching the outcome accompanying R2 performance from O1 to a new one (O2). Experiment 1 showed paired presentations of O2 with a lithium chloride (LiCl) injection resulted in a reduction in the R2 performance.

Reduction of instrumental discrimination performance by post-conditioning devaluation of discriminative stimulus: the effects of novelty in reinforcing outcome and extended training.

In three experiments the effects of post-conditioning pairings of a discriminative stimulus (Sd) with an illness-inducing agent (lithium chloride, LiCl) on subsequent discrimination performance in extinction and consumption of reinforcing outcome were investigated. Rats were trained to choose a correct lever to obtain food pellets, with a light presented on a bulb just above the correct lever serving for the Sd on each trial. After achievement of a criterion of the discrimination, animals received paired or unpaired presentations of the Sds and LiCl injection.