Prefrontal cortical mechanisms underlying delayed alternation in mice

2012 ◽  
Vol 108 (4) ◽  
pp. 1211-1222 ◽  
Author(s):  
Mark A. Rossi ◽  
Volodya Y. Hayrapetyan ◽  
Benjamin Maimon ◽  
Krystal Mak ◽  
H. Shawn Je ◽  
...  
Keyword(s):  
Prefrontal Cortex ◽  
Dorsal Hippocampus ◽  
Critical Role ◽  
Brain Slices ◽  
Projection Neurons ◽  
Patch Clamp Recording ◽  
Delayed Alternation ◽  
Delayed Alternation Task ◽  
Alternation Task

The prefrontal cortex (PFC) has been implicated in the maintenance of task-relevant information during goal-directed behavior. Using a combination of lesions, local inactivation, and optogenetics, we investigated the functional role of the medial prefrontal cortex (mPFC) in mice with a novel operant delayed alternation task. Task difficulty was manipulated by changing the duration of the delay between two sequential actions. In experiment 1, we showed that excitotoxic lesions of the mPFC impaired acquisition of delayed alternation with long delays (16 s), whereas lesions of the dorsal hippocampus and ventral striatum, areas connected with the PFC, did not produce any deficits. Lesions of dorsal hippocampus, however, significantly impaired reversal learning when the rule was changed from alternation to repetition. In experiment 2, we showed that local infusions of muscimol (an agonist of the GABAA receptor) into mPFC impaired performance even when the animal was well trained, suggesting that the mPFC is critical not only for acquisition but also for successful performance. In experiment 3, to examine the mechanisms underlying the role of GABAergic inhibition, we used Cre-inducible Channelrhodopsin-2 to activate parvalbumin (PV)-expressing GABAergic interneurons in the mPFC of PV-Cre transgenic mice as they performed the task. Using whole cell patch-clamp recording, we demonstrated that activation of PV-expressing interneurons in vitro with blue light in brain slices reliably produced spiking and inhibited nearby pyramidal projection neurons. With similar stimulation parameters, in vivo stimulation significantly impaired delayed alternation performance. Together these results demonstrate a critical role for the mPFC in the acquisition and performance of the delayed alternation task.

Effects of rat medial prefrontal cortex temporal inactivation on a delayed alternation task

2001 ◽  
Vol 315 (3) ◽  
pp. 129-132 ◽  
Author(s):  
Yoshinori Izaki ◽  
Kiyoyuki Maruki ◽  
Koji Hori ◽  
Masahiko Nomura
Keyword(s):  
Prefrontal Cortex ◽  
Medial Prefrontal Cortex ◽  
Delayed Alternation ◽  
Delayed Alternation Task ◽  
Alternation Task

Increase of Extracellular Dopamine in Primate Prefrontal Cortex During a Working Memory Task

1997 ◽  
Vol 78 (5) ◽  
pp. 2795-2798 ◽  
Author(s):  
Masataka Watanabe ◽  
Tohru Kodama ◽  
Kazuo Hikosaka
Keyword(s):  
Working Memory ◽  
Prefrontal Cortex ◽  
Cognitive Processes ◽  
Memory Task ◽  
Dopamine Level ◽  
Control Task ◽  
Extracellular Dopamine ◽  
Delayed Alternation ◽  
Delayed Alternation Task ◽  
Alternation Task

Watanabe, Masataka, Tohru Kodama, and Kazuo Hikosaka. Increase of extracellular dopamine in primate prefrontal cortex during a working memory task. J. Neurophysiol. 78: 2795–2798, 1997. The dopamine innervation of the prefrontal cortex is involved importantly in cognitive processes, such as tested in working memory tasks. However, there have been no studies directly investigating prefrontal dopamine levels in relation to cognitive processes. We measured frontal extracellular dopamine concentration using in vivo microdialysis in monkeys performing in a delayed alternation task as a typical working memory paradigm and in a sensory-guided control task. We observed a significant increase in dopamine level in the delayed alternation task as compared both with the sensory-guided control task and the basal resting level. The increase was seen in the dorsolateral prefrontal but not in the arcuate or orbitofrontal areas. The increase appeared to reflect the working memory component of the task and was observed mainly in the lip areas of principal sulcus. Although there was no significant difference in dopamine level between delayed alternation and sensory-guided control tasks in the premotor area, significant increases in dopamine concentration were observed during both tasks as compared with the basal resting level, indicating the importance of premotor dopamine for the motor response itself.

Effects of rat ventral and dorsal hippocampus temporal inactivation on delayed alternation task

2001 ◽  
Vol 895 (1-2) ◽  
pp. 273-276 ◽  
Author(s):  
Kiyoyuki Maruki ◽  
Yoshinori Izaki ◽  
Koji Hori ◽  
Masahiko Nomura ◽  
Toshio Yamauchi
Keyword(s):  
Dorsal Hippocampus ◽  
Delayed Alternation ◽  
Delayed Alternation Task ◽  
Alternation Task

Alcohol Dependence Conceptualized as a Stress Disorder

2019 ◽  
pp. 198-220
Author(s):  
Leandro F. Vendruscolo ◽  
George F. Koob
Keyword(s):  
Prefrontal Cortex ◽  
Alcohol Use ◽  
Alcohol Dependence ◽  
Glucocorticoid Receptors ◽  
Critical Role ◽  
Emotional States ◽  
Brain Circuits ◽  
Negative Emotional State ◽  
Alcohol Alcohol

Alcohol use disorder is a chronically relapsing disorder that involves (1) compulsivity to seek and take alcohol, (2) difficulty in limiting alcohol intake, and (3) emergence of a negative emotional state (e.g., dysphoria, anxiety, irritability) in the absence of alcohol. Alcohol addiction encompasses a three-stage cycle that becomes more intense as alcohol use progresses: binge/intoxication, withdrawal/negative affect, and preoccupation/anticipation. These stages engage neuroadaptations in brain circuits that involve the basal ganglia (reward hypofunction), extended amygdala (stress sensitization), and prefrontal cortex (executive function disorder). This chapter discusses key neuroadaptations in the hypothalamic and extrahypothalamic stress systems and the critical role of glucocorticoid receptors. These neuroadaptations contribute to negative emotional states that powerfully drive compulsive alcohol drinking and seeking. These changes in association with a disruption of prefrontal cortex function that lead to cognitive deficits and poor decision making contribute to the chronic relapsing nature of alcohol dependence.

The Role of the Medial Prefrontal Cortex in Moderating Neural Representations of Self and Other in Primates

2021 ◽  
Vol 44 (1) ◽  
Author(s):  
Masaki Isoda
Keyword(s):  
Prefrontal Cortex ◽  
Medial Prefrontal Cortex ◽  
Critical Role ◽  
Autism Spectrum ◽  
Annual Review ◽  
Publication Date ◽  
Self And Other ◽  
Neural Representations ◽  
The Social

As a frontal node in the primate social brain, the medial prefrontal cortex (MPFC) plays a critical role in coordinating one's own behavior with respect to that of others. Current literature demonstrates that single neurons in the MPFC encode behavior-related variables such as intentions, actions, and rewards, specifically for self and other, and that the MPFC comes into play when reflecting upon oneself and others. The social moderator account of MPFC function can explain maladaptive social cognition in people with autism spectrum disorder, which tips the balance in favor of self-centered perspectives rather than taking into consideration the perspective of others. Several strands of evidence suggest a hypothesis that the MPFC represents different other mental models, depending on the context at hand, to better predict others’ emotions and behaviors. This hypothesis also accounts for aberrant MPFC activity in autistic individuals while they are mentalizing others. Expected final online publication date for the Annual Review of Neuroscience, Volume 44 is July 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

scholarly journals The Role of VMPC in Metamemorial Judgments of Content Retrievability

2005 ◽  
Vol 17 (5) ◽  
pp. 832-846 ◽  
Author(s):  
David M. Schnyer ◽  
Lindsay Nicholls ◽  
Mieke Verfaellie
Keyword(s):  
Prefrontal Cortex ◽  
Medial Prefrontal Cortex ◽  
Critical Role ◽  
Structural Equations ◽  
Feeling Of Knowing ◽  
Ventral Medial Prefrontal Cortex ◽  
Memory Contents ◽  
Frontal Lesions ◽  
Content Accessibility

Making judgments about the retrievability of information is a critical part of the metamemory processes engaged during remembering. A recent study of patients with frontal lesions suggests that ventral medial prefrontal cortex (VMPC) plays a critical role in such judgments [Schnyer, D. M., Verfaellie, M., Alexander, M. P., Lafleche, G., Nicholls, L., & Kaszniak, A. W. A role for right medial prefrontal cortex in accurate feeling of knowing judgments: Evidence from patients with lesions to frontal cortex. Neuropsychologia, 42, 957–966, 2004]. The observed impairment was thought to reflect an inability to determine the accessibility of memory contents. To further examine the neuroanatomical basis of content accessibility assessment, we used fMRI in an episodic feeling-of-knowing (FOK) paradigm. Participants were asked to make trial-by-trial predictions about the retrievability of the final word that completed studied sentences and then to select the correct completion from among alternatives. Results indicated that the VMPC is engaged during accurate FOK judgments and its activation is modulated by retrieval rating. Structural equations modeling supported the notion that VMPC, as part of a broader left hemisphere network involved in memory retrieval, monitors the output of the retrieval process. More generally, VMPC may participate in metacognitive processes that allow for the comparison of available data against an internal model.

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