Altering Perceived Context: Transportation Cues Influence Novelty-Induced Context Exploration.

Context is the milieu in which everything occurs. Many research studies consider context, or even explicitly manipulate it; yet it remains challenging to characterize. We know that a context surrounds and influences tasks; however, the boundaries of its influence are difficult to define.

Sex differences in conditioned orienting and the role of estradiol in addiction-related behaviors.

Conditioned orienting response (OR) is a form of cue-directed behavior thought to indicate increased attentional and/or motivational processing of reward-associated stimuli. OR as a phenotype has been shown to predict both direct drug proclivity in female rats and behaviors indirectly related to drug proclivity in male rats, but no extant research has compared males and females in terms of their OR behavior or its notable substrates. As females are at increased risk for substance abuse, and the ovarian hormone estradiol is often cited as a driving factor for this predilection, it is important to characterize sex differences between males and females and explore what, if any, contribution estradiol has in behaviors which predict substance abuse.

Methylene Blue Preserves Cytochrome Oxidase Activity and Prevents Neurodegeneration and Memory Impairment in Rats With Chronic Cerebral Hypoperfusion.

Chronic cerebral hypoperfusion in neurocognitive disorders diminishes cytochrome oxidase activity leading to neurodegenerative effects and impairment of learning and memory. Methylene blue at low doses stimulates cytochrome oxidase activity and may thus counteract the adverse effects of cerebral hypoperfusion. However, the effects of methylene blue on cytochrome oxidase activity during chronic cerebral hypoperfusion have not been described before.

Mapping the estrous cycle to context-specific extinction memory.

In Pavlovian renewal paradigms, intact female rats have previously failed to exhibit renewal of appetitive behavior after extinction. However, when treated with exogenous estradiol, female rats exhibit robust renewal behavior. The current study aims to investigate whether the estrous cycle can influence renewal of appetitive behaviors and activity in brain areas known to support the renewal effect.

Conserved features of anterior cingulate networks support observational learning across species.

The ability to observe, interpret, and learn behaviors and emotions from conspecifics is crucial for survival, as it bypasses direct experience to avoid potential dangers and maximize rewards and benefits. The anterior cingulate cortex (ACC) and its extended neural connections are emerging as important networks for the detection, encoding, and interpretation of social signals during observational learning. Evidence from rodents and primates (including humans) suggests that the social interactions that occur while individuals are exposed to important information in their environment lead to transfer of information across individuals that promotes adaptive behaviors in the form of either social affiliation, alertness, or avoidance.

Memory boundaries: opening a window inspired by reconsolidation to treat anxiety, trauma-related, and addiction disorders.

Pioneering research over the past two decades has shown that memories are far more malleable than we once thought, thereby highlighting the potential for new clinical avenues for treatment of psychopathology. We first briefly review the historical foundation of memory reconsolidation-a concept that refers to hypothetical processes that occur when a memory is retrieved and restored. Then, we provide an overview of the basic research on memory reconsolidation that has been done with humans and other animals, focusing on models of fear, anxiety-related disorders, and addiction, from the perspective that they all involve disorders of memory.

Insights from social transmission of information in rodents.

Direct exposure to stimuli in their environment is not the only way that animals learn about important information. Individuals can infer fear from a social context through observation. Like humans, rats are very social animals, and may learn to infer information about their environment through their interactions with conspecifics.

Daily consumption of methylene blue reduces attentional deficits and dopamine reduction in a 6-OHDA model of Parkinson's disease.

Recently, alternative drug therapies for Parkinson's disease (PD) have been investigated as there are many shortcomings of traditional dopamine-based therapies including difficulties in treating cognitive and attentional dysfunction. A promising therapeutic avenue is to target mitochondrial dysfunction and oxidative stress in PD. One option might be the use of methylene blue (MB), an antioxidant and metabolic enhancer.

Preventing the return of fear using reconsolidation updating and methylene blue is differentially dependent on extinction learning.

Many factors account for how well individuals extinguish conditioned fears, such as genetic variability, learning capacity and conditions under which extinction training is administered. We predicted that memory-based interventions would be more effective to reduce the reinstatement of fear in subjects genetically predisposed to display more extinction learning. We tested this hypothesis in rats genetically selected for differences in fear extinction using two strategies: (1) attenuation of fear memory using post-retrieval extinction training, and (2) pharmacological enhancement of the extinction memory after extinction training by low-dose USP methylene blue (MB).

Reconsolidation-Extinction Interactions in Fear Memory Attenuation: The Role of Inter-Trial Interval Variability.

Fear extinction typically results in the formation of a new inhibitory memory that suppresses the original conditioned response. Evidence also suggests that extinction training during a retrieval-induced labile period results in integration of the extinction memory into the original fear memory, rendering the fear memory less susceptible to reinstatement. Here we investigated the parameters by which the retrieval-extinction paradigm was most effective in memory updating.

Assessing Fear Following Retrieval + Extinction Through Suppression of Baseline Reward Seeking vs. Freezing.

Freezing has become the predominant measure used in rodent studies of conditioned fear, but conditioned suppression of reward-seeking behavior may provide a measure that is more relevant to human anxiety disorders; that is, a measure of how fear interferes with the enjoyment of pleasurable activities. Previous work has found that an isolated presentation of a fear conditioned stimulus (CS) prior to extinction training (retrieval + extinction) results in a more robust and longer-lasting reduction in fear. The objective of this study was to assess whether the retrieval + extinction effect is evident using conditioned suppression of reward seeking, operationalized as a reduction in baseline licking (without prior water deprivation) for a 10% sucrose solution.

Exercise Augmentation of Exposure Therapy for PTSD: Rationale and Pilot Efficacy Data.

Brain-derived neurotrophic factor (BDNF) is associated with synaptic plasticity, which is crucial for long-term learning and memory. Some studies suggest that people suffering from anxiety disorders show reduced BDNF relative to healthy controls. Lower BDNF is associated with impaired learning, cognitive deficits, and poor exposure-based treatment outcomes.

Therapeutic benefits of methylene blue on cognitive impairment during chronic cerebral hypoperfusion.

Chronic cerebral hypoperfusion, a risk factor for mild cognitive impairment and Alzheimer's disease, affects mitochondrial respiration and memory consolidation. Therefore, drugs that improve mitochondrial function may be appropriate cognitive treatments for cerebral hypoperfusion. Methylene blue (MB) crosses the blood-brain barrier and at low doses serves as an electron cycler in the mitochondrial electron transport chain.

Predictability and heritability of individual differences in fear learning.

Our objective was to characterize individual differences in fear conditioning and extinction in an outbred rat strain, to test behavioral predictors of these individual differences, and to assess their heritability. We fear-conditioned 100 Long-Evans rats, attempted to extinguish fear the next day, and tested extinction recall on the third day. The distribution of freezing scores after fear conditioning was skewed, with most rats showing substantial freezing; after fear extinction, the distribution was bimodal with most rats showing minimal freezing, but a substantial portion showing maximal freezing.

Erasing fear memories with extinction training.

Decades of behavioral studies have confirmed that extinction does not erase classically conditioned fear memories. For this reason, research efforts have focused on the mechanisms underlying the development of extinction-induced inhibition within fear circuits. However, recent studies in rodents have uncovered mechanisms that stabilize and destabilize fear memories, opening the possibility that extinction might be used to erase fear memories.

Optical activation of lateral amygdala pyramidal cells instructs associative fear learning.

Humans and animals can learn that specific sensory cues in the environment predict aversive events through a form of associative learning termed fear conditioning. This learning occurs when the sensory cues are paired with an aversive event occurring in close temporal proximity. Activation of lateral amygdala (LA) pyramidal neurons by aversive stimuli is thought to drive the formation of these associative fear memories; yet, there have been no direct tests of this hypothesis.

Fear and safety learning differentially affect synapse size and dendritic translation in the lateral amygdala.

Fear learning is associated with changes in synapse strength in the lateral amygdala (LA). To examine changes in LA dendritic spine structure with learning, we used serial electron microscopy to re-construct dendrites after either fear or safety conditioning. The spine apparatus, a smooth endoplasmic reticulum (sER) specialization found in very large spines, appeared more frequently after fear conditioning.

Motor maps, seizures, and behaviour.

Atypically organised motor maps have been described in some people with epilepsy and we have modelled this in rats. Our goal is to more fully understand the mechanisms responsible for seizure-induced functional brain reorganisation and to reverse their effects. Here we present an overview of the relationship between neocortical motor maps, seizures, and interictal behaviour.

FGF-2-induced functional improvement from neonatal motor cortex injury via corticospinal projections.

The administration of basic fibroblast growth factor (FGF-2) to rats with postnatal 10 (P10) motor cortex (MCx) lesions results in functional improvements accompanied with filling of the previously lesioned area with tissue. In the present experiment, we tested the prediction that FGF-2 induces functional recovery by promoting meaningful reconnection of neurons from the filled region to the periphery. Rats received bilateral MCx lesions on P10 and subcutaneous injections of either vehicle or FGF-2 for 7 days beginning on P11.

Cortical stimulation improves skilled forelimb use following a focal ischemic infarct in the rat.

Improving functional recovery following cerebral strokes in humans will likely involve augmenting brain plasticity. This study examined skilled forelimb behavior, neocortical evoked potentials, and movement thresholds to assess cortical electrical stimulation concurrent with rehabilitative forelimb usage following a focal ischemic insult. Adult rats were trained on a task that required skilled usage of both forelimbs.

Functional organization of adult motor cortex is dependent upon continued protein synthesis.

The functional organization of adult cerebral cortex is characterized by the presence of highly ordered sensory and motor maps. Despite their archetypical organization, the maps maintain the capacity to rapidly reorganize, suggesting that the neural circuitry underlying cortical representations is inherently plastic. Here we show that the circuitry supporting motor maps is dependent upon continued protein synthesis.