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The hippocampus plays a central role in spatial and contextual learning and memory, however relatively little is known about the specific contributions of parahippocampal structures that interface with the hippocampus. The postsubiculum (PoSub) is reciprocally connected with a number of hippocampal, parahippocampal and subcortical structures that are involved in spatial learning and memory. In addition, behavioral data suggest that PoSub is needed for optimal performance during tests of spatial memory. Together, these data suggest that PoSub plays a prominent role in spatial navigation. Currently it is unknown whether the PoSub is needed for other forms of learning and memory that also require the formation of associations among multiple environmental stimuli. To address this gap in the literature we investigated the role of PoSub in Pavlovian fear conditioning. In Experiment 1 male rats received either lesions of PoSub or Sham surgery prior to training in a classical fear conditioning procedure. On the training day a tone was paired with foot shock three times. Conditioned fear to the training context was evaluated 24 hr later by placing rats back into theconditioning chamber without presenting any tones or shocks. Auditory fear was assessed on the third day by presenting the auditory stimulus in a novel environment (no shock). PoSub-lesioned rats exhibited impaired acquisition of the conditioned fear response as well as impaired expression of contextual and auditory fear conditioning. In Experiment 2, PoSub lesions were made 1 day after training to specifically assess the role of PoSub in fear memory. No deficits in the expression of contextual fear were observed, but freezing to the tone was significantly reduced in PoSub-lesioned rats compared to shams. Together, these results indicate that PoSub is necessary for normal acquisition of conditioned fear, and that PoSub contributes to the expression of auditory but not contextual fear memory. © 2011 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

When several different objects are presented, visual objects are perceived correctly only if their features are identified and then bound together. Illusory-conjunction errors result when an object is correctly identified but is combined incorrectly. The parietal cortex (PC) has been shown repeatedly to play an important role in feature binding. The present study builds on a series of recent studies that have made use of visual search paradigms to elucidate the neural system involved in feature binding. This experiment attempts to define the role the PC plays in binding the properties of a visual object that varies on the features of color and size in rats. Rats with PC lesions or control surgery were exposed to three blocks of 20 trials administered over a 1-week period, with each block containing 10-one feature and 10-two feature trials. The target object consisted of one color object (e.g., black and white) and one size object (e.g., short and tall). Of the 10 one feature trials, five of the trials were tailored specifically for size discrimination and five for color discrimination. In the two-feature condition, the animal was required to locate the targeted object among four objects with two objects differing in size and two objects differing in color. The results showed that the PC lesioned compared to control rats had difficulty in learning the one and two features components of the task and the rats also performed more poorly on the one vs. two feature components of the task. Based on a subsequent error analysis for color and size, the results showed a significant increase in illusory conjunction errors for the PC lesioned rats relative to controls for color and relative to color discrimination, suggesting that the PC may support feature binding as it relates to color. There was an increase in illusory conjunctions errors for both the PC lesioned and control animals for size, but this appeared to be due to highly variable performance with size discrimination. Overall these results suggest that the PC rats display performance errors that appear to be consistent with the notion of illusory conjunction errors. [ABSTRACT FROM AUTHOR]

The dorsolateral prefrontal cortex (PFC) and posterior parietal cortex (PPC) are two parts of a broader brain network involved in the control of cognitive functions such as working-memory, spatial attention, and decision-making. The two areas share many functional properties and exhibit similar patterns of activation during the execution of mental operations. However, neurophysiological experiments in non-human primates have also documented subtle differences, revealing functional specialization within the fronto-parietal network. These differences include the ability of the PFC to influence memory performance, attention allocation, and motor responses to a greater extent, and to resist interference by distracting stimuli. In recent years, distinct cellular and anatomical differences have been identified, offering insights into how functional specialization is achieved. This article reviews the common functions and functional differences between the PFC and PPC, and their underlying mechanisms. [ABSTRACT FROM AUTHOR]

ACh release into the rodent prefrontal cortex is predictive of successful performance of cue detection tasks, yet the cellular mechanisms underlying cholinergic modulation of cortical function are not fully understood. Prolonged ("tonic") muscarinic ACh receptor (mAChR) activation increases the excitability of cortical pyramidal neurons, whereas transient ("phasic") mAChR activation generates inhibitory and/or excitatory responses, depending on neuron subtype. These cholinergic effects result from activation of "M1-like" mAChRs (M1, M3, and M5 receptors), but the specific receptor subtypes involved are not known. We recorded from cortical pyramidal neurons from wild-type mice and mice lacking M1, M3, and/or M5 receptors to determine the relative contribution of M1-like mAChRs to cholinergic signaling in the mouse prefrontal cortex. Wild-type neurons in layer 5 were excited by tonic mAChR stimulation, and had biphasic inhibitory followed by excitatory, responses to phasic ACh application. Pyramidal neurons in layer 2/3 were substantially less responsive to tonic and phasic cholinergic input. Cholinergic effects were largely absent in neurons from mice lacking M1 receptors, but most were robust in neurons lacking M3, M5, or both M3 and M5 receptors. The exception was tonic cholinergic suppression of the afterhyperpolarization in layer 5 neurons, which was absent in cells lacking either M1 or M3 receptors. Finally, we confirm a role for M1 receptors in behavior by demonstrating cue detection deficits in M1-lacking mice. Together, our results demonstrate that M1 receptors facilitate cue detection behaviors and are both necessary and sufficient for most direct effects of ACh on pyramidal neuron excitability. [ABSTRACT FROM AUTHOR]

The perirhinal (PER) and postrhinal (POR) cortices, two components of the medial temporal lobe memory system, are reciprocally connected with the hippocampus both directly and via the entorhinal cortex. Damage to PER or POR before or shortly after training on a contextual fear conditioning task causes deficits in the subsequent expression of contextual fear, implicating these regions in the acquisition or expression of contextual memory. Here, we examined the contribution of PER and POR to the processing of remotely learned contextual information. Male Long-Evans rats were trained in an unsignaled contextual fear conditioning paradigm. After training, rats received bilateral neurotoxic lesions to PER or POR or sham control surgeries at three different training-to-lesion intervals: 1,28, or 100 d after training. Two weeks after surgery, lesioned and control rats were returned to the training context to assess contextual fear as measured by freezing. Rats with PER or POR damage froze significantly less in the training context than control rats but were not different from each other. The severity of the deficit did not differ across training-to- lesion intervals for any group. This pattern of deficits differs from that of posttraining hippocampal lesions, for which longer training-to- lesion intervals produce significantly more fear-conditioned contextual freezing than shorter training-to-lesion intervals. In the absence of such a retrograde gradient in the present study, our interpretation is that PER and POR have an ongoing role in the storage or retrieval of representations for context. Alternatively, these regions may be involved in a more extended consolidation process that becomes apparent beyond 100 d after learning. [ABSTRACT FROM AUTHOR]

Abstract: The endocannabinoid system appears to have an important role in specific aspects of learning and memory, yet there has been no systematic study of the role of cannabinoid receptors in contextual fear conditioning. The present study examined the effects of cannabinoid CB1 receptor blockade on the acquisition, consolidation, and expression of contextual fear using the selective cannabinoid CB1 receptor antagonist AM251. AM251 produced a decrease in the expression of contextual fear when administered prior to training, testing, or both. This effect was observed when footshock was signaled by an auditory cue but not in an unsignaled shock version of the task. Moreover, blocking cannabinoid CB1 receptors had no effect on consolidation of contextual memory regardless of the conditioning paradigm. These data indicate that inhibition of cannabinoid CB1 receptors produces specific deficits in processing contextual information and that the effects of CB1 antagonists on contextual learning may differ from effects on other types of learning. [Copyright &y& Elsevier]

• Examined the role of the postrhinal cortex in the retrieval of auditory fear conditioning. • Inactivation of the postrhinal cortex impaired retrieval of auditory fear conditioning following extinction. • Inactivation of the postrhinal cortex also impaired retrieval of auditory fear conditioning that had not been extinguished. The postrhinal cortex (POR), the rodent homologue of the primate parahippocampal cortex (PHC), has been implicated in contextual and spatial processing. For instance, prior studies have demonstrated that permanent lesions of POR impair contextual fear conditioning. In contrast, permanent lesions of POR, specifically prior to training, do not impact auditory fear conditioning. In the current experiments, we examined the role of POR in the expression of auditory fear conditioning by using chemogenetics to silence neural activity in POR at the time of retrieval testing. Considering that extinction is context-dependent, and POR contributes to contextual memory, we hypothesized that POR would be necessary for expression of auditory fear conditioning following extinction. We found that POR inactivation during retrieval impaired freezing to an auditory cue that was tested in the conditioning context (A) after it had been extinguished in a different context (B). However, the involvement of POR was not specific to extinction. POR inactivation also impaired freezing to an auditory fear cue that had not undergone extinction. Thus, while prior studies have identified a role for POR in contextual fear conditioning, the current findings extend the functional role of POR to include the expression of auditory fear conditioning. [ABSTRACT FROM AUTHOR]

• RSC inactivation impaired retrieval of remotely acquired delay fear conditioning (FC). • RSC inactivation did not impair retrieval of recently acquired delay FC. • RSC inactivation during encoding did not impair later retrieval of delay FC. Prior studies with permanent lesion methods have demonstrated a role for the retrosplenial cortex (RSC) in the retrieval of remotely, but not recently, acquired delay fear conditioning. To extend the generalizability of these prior findings, the present experiments used chemogenetics to temporarily inactivate the RSC during either retrieval or encoding of delay auditory fear conditioning. Inactivation of the RSC at the time of test impaired retrieval of a remotely conditioned auditory cue, but not a recently conditioned one. In addition, inactivation of the RSC during encoding had no impact on freezing during later retrieval testing for both a remotely and recently conditioned auditory cue. These findings indicate that the RSC contributes to the retrieval, but not encoding, of remotely acquired auditory fear conditioning, and suggest it has less of a role in both retrieval and encoding of recently acquired auditory fear conditioning. [ABSTRACT FROM AUTHOR]

Impaired activity of the hypothalamic-pituitary axis and reduced blood levels of glucocorticoids (GCs) are signature features of stress-related maladies. Recent evidence suggests a possible role of the tryptophan metabolite kynurenic acid (KYNA) in this context. Here we investigated possible causal relationships in adult male rats, using stress-induced fear discrimination as a translationally relevant behavioral outcome measure. One week following adrenalectomy (ADX) or sham surgery, animals were for 2 h either physically restrained or exposed to a predator odor, which caused a much milder stress response. Extracellular KYNA levels were determined before, during and after stress by in vivo microdialysis in the prefrontal cortex. Separate cohorts underwent a fear discrimination procedure starting immediately after stress termination. Different auditory conditioned stimuli (CS) were either paired with a foot shock (CS+) or non-reinforced (CS-). One week later, fear was assessed by re-exposing the animals to each CS. Separate groups of rats were treated with the KYNA synthesis inhibitor BFF-816 prior to stress initiation to test a causal role of KYNA in fear discrimination. Restraint stress raised extracellular KYNA levels by ∼85 % in ADX rats for several hours, and these animals were unable to discriminate between CS+ and CS-. Both effects were prevented by BFF-816 and were not observed after exposure to predator odor or in sham-operated rats. These findings suggest that a causal connection exists between adrenal function, stress-induced KYNA increases, and behavioral deficits. Pharmacological inhibition of KYNA synthesis may therefore be an attractive, novel option for the treatment of stress-related disorders., Competing Interests: Declaration of competing interest RS is a co-founder of KyNexis BV, which focuses on the pharmacological manipulation of kynurenine pathway metabolism for therapeutic purposes. This may be considered a potential competing interest. The remaining authors declare that they have no known competing financial interests or personal relationships that could have influenced the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Technological advances over the last decade are changing the face of behavioral neuroscience research. Here we review recent work on the use of one such transformative tool in behavioral neuroscience research, chemogenetics (or Designer Receptors Exclusively Activated by Designer Drugs, DREADDS). As transformative technologies such as DREADDs are introduced, applied, and refined, their utility in addressing complex questions about behavior and cognition becomes clear and exciting. In the behavioral neuroscience field, remarkable new findings now regularly appear as a result of the ability to monitor and intervene in neural processes with high anatomical precision as animals behave in complex task environments. As these new tools are applied to behavioral questions, individualized procedures for their use find their way into diverse labs. Thus, "tips of the trade" become important for wide dissemination not only for laboratories that are using the tools but also for those who are interested in incorporating them into their own work. Our aim is to provide an up-to-date perspective on how the DREADD technique is being used for research on learning and memory, decision making, and goal-directed behavior, as well as to provide suggestions and considerations for current and future users based on our collective experience. (PsycINFO Database Record, ((c) 2016 APA, all rights reserved).)

Substantial research has established that exercise can improve mental health and cognitive function in both human and non-human animals. Exercise has been shown to improve learning and memory in both adult and juvenile animals, with larger and more durable effects associated with exercising during development. Exercise during the gestational period has also been shown to improve cognition in the offspring. Several recent studies indicate that the offspring of mothers that exercised during pregnancy exhibit improved learning and memory and decreased anxiety-like behaviors. These behavioral changes are accompanied by increased neurogenesis, neurotrophic factor expression, and neuronal activity in the offspring. This review summarizes the current literature regarding the effects of maternal exercise in rodents and presents avenues for future research to reveal the biological mechanism(s) through which maternal exercise changes the brain and behavior of the offspring.