Sex-dependent differences in the ability of nicotine to modulate discrimination learning and cognitive flexibility in mice.

Nicotine, an addictive compound found in tobacco, functions as an agonist of nicotinic acetylcholine receptors (nAChRs) in the brain. Interestingly, nicotine has been reported to act as a cognitive enhancer in both human subjects and experimental animals. However, its effects in animal studies have not always been consistent, and sex differences have been identified in the effects of nicotine on several behaviors.

Clozapine N-oxide, compound 21, and JHU37160 do not influence effortful reward-seeking behavior in mice.

Rationale: Clozapine N-oxide (CNO) has been developed as a ligand to selectively activate designer receptors exclusively activated by designer drugs (DREADDs). However, previous studies have revealed that peripherally injected CNO is reverse-metabolized into clozapine, which, in addition to activating DREADDs, acts as an antagonist at various neurotransmitter receptors, suggesting potential off-target effects of CNO on animal physiology and behaviors. Recently, second-generation DREADD agonists compound 21 (C21) and JHU37160 (J60) have been developed, but their off-target effects are not fully understood.

α4-Containing GABA Receptors on DRD2 Neurons of the Nucleus Accumbens Mediate Instrumental Responding for Conditioned Reinforcers and Its Potentiation by Cocaine.

Extrasynaptic GABA receptors (GABARs) composed of α4, β, and δ subunits mediate GABAergic tonic inhibition and are potential molecular targets in the modulation of behavioral responses to natural and drug rewards. These GABARs are highly expressed within the nucleus accumbens (NAc), where they influence the excitability of the medium spiny neurons. Here, we explore their role in modulating behavioral responses to food-conditioned cues and the behavior-potentiating effects of cocaine.

Dual Roles for Nucleus Accumbens Core Dopamine D1-Expressing Neurons Projecting to the Substantia Nigra Pars Reticulata in Limbic and Motor Control in Male Mice.

The nucleus accumbens (NAc) is a critical component of a limbic basal ganglia circuit that is thought to play an important role in decision-making and the processing of rewarding stimuli. As part of this circuit, dopamine D1 receptor-expressing medium spiny neurons (D1-MSNs) of the NAc core are known to send a major projection to the substantia nigra pars reticulata (SNr). However, the functional role of this SNr-projecting NAc D1-MSN (NAc-SNr) pathway is still largely uncharacterized.

Error-related signaling in nucleus accumbens D2 receptor-expressing neurons guides inhibition-based choice behavior in mice.

Learned associations between environmental cues and the outcomes they predict (cue-outcome associations) play a major role in behavioral control, guiding not only which responses we should perform, but also which we should inhibit, in order to achieve a specific goal. The encoding of such cue-outcome associations, as well as the performance of cue-guided choice behavior, is thought to involve dopamine D1 and D2 receptor-expressing medium spiny neurons (D1-/D2-MSNs) of the nucleus accumbens (NAc). Here, using a visual discrimination task in male mice, we assessed the role of NAc D1-/D2-MSNs in cue-guided inhibition of inappropriate responding.

Quantifying Exposure and Intra-Individual Reliability of High-Speed and Sprint Running During Sided-Games Training in Soccer Players: A Systematic Review and Meta-analysis.

Background: Sided games (i.e., small sided, medium sided, large sided) involve tactical, technical, physical, and psychological elements and are commonly implemented in soccer training.

Importin α3 (KPNA3) Deficiency Augments Effortful Reward-Seeking Behavior in Mice.

Importin α3 (Gene: , the ortholog of human Importin α4) is a member of the importin α family and participates in nucleocytoplasmic transport by forming trimeric complexes between cargo proteins and importin β1. Evidence from human studies has indicated that single nucleotide polymorphisms (SNP) in the gene are associated with the occurrence of several psychiatric disorders accompanied by abnormal reward-related behavior, including schizophrenia, major depression, and substance addiction. However, the precise roles of importin α3 in controlling reward processing and motivation are still unclear.

Nucleus Accumbens Core Dopamine D2 Receptor-Expressing Neurons Control Reversal Learning but Not Set-Shifting in Behavioral Flexibility in Male Mice.

The ability to use environmental cues to flexibly guide responses is crucial for adaptive behavior and is thought to be controlled within a series of cortico-basal ganglia-thalamo-cortical loops. Previous evidence has indicated that different prefrontal cortical regions control dissociable aspects of behavioral flexibility, with the medial prefrontal cortex (mPFC) necessary for the ability to shift attention to a novel strategy (set-shifting) and the orbitofrontal cortex (OFC) necessary for shifting attention between learned stimulus-outcome associations (reversal learning). The nucleus accumbens (NAc) is a major downstream target of both the mPFC and the OFC; however, its role in controlling reversal learning and set-shifting abilities is still unclear.

Effects of Importin α1/KPNA1 deletion and adolescent social isolation stress on psychiatric disorder-associated behaviors in mice.

Importin α1/KPNA1 is a member of the Importin α family widely present in the mammalian brain and has been characterized as a regulator of neuronal differentiation, synaptic functionality, and anxiety-like behavior. In humans, a de novo mutation of the KPNA1 (human Importin α5) gene has been linked with schizophrenia; however, the precise roles of KPNA1 in disorder-related behaviors are still unknown. Moreover, as recent studies have highlighted the importance of gene-environment interactions in the development of psychiatric disorders, we investigated the effects of Kpna1 deletion and social isolation stress, a paradigm that models social stress factors found in human patients, on psychiatric disorder-related behaviors in mice.

Natural and Artificial Intelligence: A brief introduction to the interplay between AI and neuroscience research.

Neuroscience and artificial intelligence (AI) share a long history of collaboration. Advances in neuroscience, alongside huge leaps in computer processing power over the last few decades, have given rise to a new generation of in silico neural networks inspired by the architecture of the brain. These AI systems are now capable of many of the advanced perceptual and cognitive abilities of biological systems, including object recognition and decision making.

Parallel and hierarchical neural mechanisms for adaptive and predictive behavioral control.

Our brain can be recognized as a network of largely hierarchically organized neural circuits that operate to control specific functions, but when acting in parallel, enable the performance of complex and simultaneous behaviors. Indeed, many of our daily actions require concurrent information processing in sensorimotor, associative, and limbic circuits that are dynamically and hierarchically modulated by sensory information and previous learning. This organization of information processing in biological organisms has served as a major inspiration for artificial intelligence and has helped to create in silico systems capable of matching or even outperforming humans in several specific tasks, including visual recognition and strategy-based games.

The school playground environment as a driver of primary school children's physical activity behaviour: A direct observation case study.

The school playground can promote PA for large numbers of children. This study identifies areas of the playground that children visited at break-times, the decisions according to gender and the influence of contextual and environmental variables on PA levels. The playground of a culturally diverse primary school was observed during morning break-times and lunchtimes.

Effect of Sand on Knee Load During a Single-Leg Jump Task: Implications for Injury Prevention and Rehabilitation Programs.

Richardson, MC, Murphy, S, Macpherson, T, English, B, Spears, I, and Chesterton, P. Effect of sand on knee load during a single-leg jump task: implications for injury prevention and rehabilitation programs. J Strength Cond Res 34(11): 3164-3172, 2020-The purpose of the study was to determine potential differences in landing strategies and subsequent joint loads at the knee (knee abduction moment [KAM], anterior-posterior [AP] tibial translation, and total knee shear force) when jumping onto sand and firm ground from both a level surface and a 30-cm height.

Systematic Reductions in Differential Ratings of Perceived Exertion Across a 2-Week Repeated-Sprint-Training Intervention That Improved Soccer Players' High-Speed-Running Abilities.

Purpose: To quantify changes in differential ratings of perceived exertion (dRPE) across a 2-wk repeated-sprint-training intervention that improved high-intensity intermittent-running ability and linear speed of semiprofessional soccer players.

Methods: Thirteen players completed 3 (sessions 1-3) or 4 (sessions 4-6) sets of 7 sprints (group 1 [n = 7]: 30-m straight; group 2 [n = 6]: 2 × 10-m shuttle), with 20 s and 4 min of recovery between sprints and sets, respectively. Postset perceptions of breathlessness (RPE-B) and leg-muscle exertion (RPE-L) were rated using the CR100 scale.

Neurotransmission through dopamine D1 receptors is required for aversive memory formation and Arc activation in the cerebral cortex.

Dopaminergic neurotransmission is considered to play an important role not only in reward-based learning, but also in aversive learning. Here, we investigated the role of dopaminergic neurotransmission via dopamine D1 receptors (D1Rs) in aversive memory formation in a passive avoidance test using D1R knockdown (KD) mice, in which the expression of D1Rs can conditionally and reversibly be controlled by doxycycline (Dox) treatment. We also performed whole-brain imaging after aversive footshock stimulation in activity-regulated cytoskeleton protein (Arc)-dVenus D1RKD mice, which were crossbred from Arc-dVenus transgenic mice and D1RKD mice, to examine the distribution of Arc-controlled dVenus expression in the hippocampus and cerebral cortex during aversive memory formation.

Nucleus accumbens pathways control cell-specific gene expression in the medial prefrontal cortex.

The medial prefrontal cortex (mPFC) is a critical component of a cortico-basal ganglia-thalamo-cortical loop regulating limbic and cognitive functions. Within this circuit, two distinct nucleus accumbens (NAc) output neuron types, dopamine D1 or D2 receptor-expressing neurons, dynamically control the flow of information through basal ganglia nuclei that eventually project back to the mPFC to complete the loop. Thus, chronic dysfunction of the NAc may result in mPFC transcriptomal changes, which in turn contribute to disease conditions associated with the mPFC and basal ganglia.

Using differential ratings of perceived exertion to assess agreement between coach and player perceptions of soccer training intensity: An exploratory investigation.

We aimed to assess the coach-player agreement of subjective soccer training loads via differential ratings of perceived exertion (dRPE). The coach initially underwent quantifiable familiarisation (blackness test) with the Borg CR100 scale. Data were collected from 16 semi-professional soccer players across seven consecutive training sessions.

Adolescent psychosocial stress enhances sensitization to cocaine exposure in genetically vulnerable mice.

Development of drug addictive behaviors is modulated by both genetic and environmental risk factors. However, the molecular mechanisms remain unknown. To address the role of adolescent stress in the development of drug addiction, we combined a transgenic mouse model in which a putative dominant-negative form of DISC1 under expressional control of the prion protein promoter is used as a genetic risk factor and adolescent social isolation stress as a gene-environmental interaction (GXE).

Preproenkephalin-expressing ventral pallidal neurons control inhibitory avoidance learning.

The ventral pallidum (VP) is a critical component of the basal ganglia neurocircuitry regulating learning and decision making; however, its precise role in controlling associative learning of environmental stimuli conditioned to appetitive or aversive outcomes is still unclear. Here, we investigated the expression of preproenkephalin, a polypeptide hormone previously shown to be expressed in nucleus accumbens neurons controlling aversive learning, within GABAergic and glutamatergic VP neurons. Next, we explored the behavioral consequences of chemicogenetic inhibition or excitation of preproenkephalin-expressing VP neurons on associative learning of reward- or aversion-paired stimuli in autoshaping and inhibitory avoidance tasks, respectively.

Role of basal ganglia neurocircuitry in the pathology of psychiatric disorders.

Over the last few decades, advances in human and animal-based techniques have greatly enhanced our understanding of the neural mechanisms underlying psychiatric disorders. Many of these studies have indicated connectivity between and alterations within basal ganglia structures to be particularly pertinent to the development of symptoms associated with several of these disorders. Here we summarize the connectivity, molecular composition, and function of sites within basal ganglia neurocircuits.

Nucleus Accumbens Dopamine D1-Receptor-Expressing Neurons Control the Acquisition of Sign-Tracking to Conditioned Cues in Mice.

Following repeated pairings, the reinforcing and motivational properties (incentive salience) of a reward can be transferred onto an environmental stimulus which can then elicit conditioned responses, including Pavlovian approach behavior to the stimulus (a sign-tracking response). In rodents, acquisition of sign-tracking in autoshaping paradigms is sensitive to lesions and dopamine D1 receptor antagonism of the nucleus accumbens (NAc) of the ventral striatum. However, currently, the possible roles of dorsal striatal subregions, as well as of the two major striatal neuron types, dopamine D1-/D2-expressing medium spiny neurons (MSNs), in controlling the development of conditioned responses is still unclear and warrants further study.

Aflibercept Action in a Rabbit Model of Chronic Retinal Neovascularization: Reversible Inhibition of Pathologic Leakage With Dose-Dependent Duration.

Purpose: We establish and characterize the chronic retinal neovascularization (RNV) induced by intravitreal (IVT) injection of DL-α-aminoadipic acid (AAA) in a rabbit model and investigate the extent and duration of inhibitory actions induced by IVT aflibercept on the RNV.

Methods: Rabbits received a single IVT injection of AAA, with weekly follow-up fundus photography, fluorescein angiography (FA), and optical coherence tomography (OCT). After 10 weeks, they received a single IVT aflibercept or control injection.

The Relationships Between Internal and External Measures of Training Load and Intensity in Team Sports: A Meta-Analysis.

Background: The associations between internal and external measures of training load and intensity are important in understanding the training process and the validity of specific internal measures.

Objectives: We aimed to provide meta-analytic estimates of the relationships, as determined by a correlation coefficient, between internal and external measures of load and intensity during team-sport training and competition. A further aim was to examine the moderating effects of training mode on these relationships.