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Anticipatory activity in rat medial prefrontal cortex during a working memory task.

ABSTRACT: Working memory is a key cognitive function in which the prefrontal cortex plays a crucial role. This study aimed to show the firing patterns of a neuronal population in the prefrontal cortex of the rat in a working memory task and to explore how a neuronal ensemble encodes a working memory event.Sprague-Dawley rats were trained in a Y-maze until they reached an 80% correct rate in a working memory task. Then a 16-channel microelectrode array was implanted in the prefrontal cortex. After recovery, neuronal population activity was recorded during the task, using the Cerebus data-acquisition system. Spatio-temporal trains of action potentials were obtained from the original neuronal population signals.During the Y-maze working memory task, some neurons showed significantly increased firing rates and evident neuronal ensemble activity. Moreover, the anticipatory activity was associated with the delayed alternate choice of the upcoming movement. In correct trials, the averaged pre-event firing rate (10.86 ± 1.82 spikes/bin) was higher than the post-event rate (8.17 ± 1.15 spikes/bin) (P<0.05). However, in incorrect trials, the rates did not differ.The results indicate that the anticipatory activity of a neuronal ensemble in the prefrontal cortex may play a role in encoding working memory events.

SUBMITTER: Bai W

PROVIDER: S-EPMC5561826 | biostudies-other | 2012 Dec

REPOSITORIES: biostudies-other

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Project description:Distinct components of working memory are coordinated by different classes of inhibitory interneurons in the PFC, but the role of cholecystokinin (CCK)-positive interneurons remains enigmatic. In humans, this major population of interneurons shows histological abnormalities in schizophrenia, an illness in which deficient working memory is a core defining symptom and the best predictor of long-term functional outcome. Yet, CCK interneurons as a molecularly distinct class have proved intractable to examination by typical molecular methods due to widespread expression of CCK in the pyramidal neuron population. Using an intersectional approach in mice of both sexes, we have succeeded in labeling, interrogating, and manipulating CCK interneurons in the mPFC. Here, we describe the anatomical distribution, electrophysiological properties, and postsynaptic connectivity of CCK interneurons, and evaluate their role in cognition. We found that CCK interneurons comprise a larger proportion of the mPFC interneurons compared with parvalbumin interneurons, targeting a wide range of neuronal subtypes with a distinct connectivity pattern. Phase-specific optogenetic inhibition revealed that CCK, but not parvalbumin, interneurons play a critical role in the retrieval of working memory. These findings shine new light on the relationship between cortical CCK interneurons and cognition and offer a new set of tools to investigate interneuron dysfunction and cognitive impairments associated with schizophrenia.SIGNIFICANCE STATEMENT Cholecystokinin-expressing interneurons outnumber other interneuron populations in key brain areas involved in cognition and memory, including the mPFC. However, they have proved intractable to examination as experimental techniques have lacked the necessary selectivity. To the best of our knowledge, the present study is the first to report detailed properties of cortical cholecystokinin interneurons, revealing their anatomical organization, electrophysiological properties, postsynaptic connectivity, and behavioral function in working memory.

Project description:Background: Transcranial direct current stimulation (tDCS) has been shown to be an inexpensive, safe, and effective way of augmenting a variety of cognitive abilities. Relatively recent advances in neuroimaging technology have provided the ability to measure brain activity concurrently during active brain stimulation rather than after stimulation. The effects on brain activity elicited by tDCS during active tDCS reported by initial studies have been somewhat conflicted and seemingly dependent on whether a behavioral improvement was observed. Objective: The current study set out to address questions regarding behavioral change, within and between-participant designs as well as differentiating the effects on hemodynamic amplitude and baseline during active tDCS stimulation. Methods: We tested the effects of transcranial direct current stimulation (tDCS) on anterior hemodynamics in prefrontal cortex during performance on a spatial memory task. Prefrontal cortex activity was measured with functional near infrared spectroscopy (fNIRS), a wearable and portable neuroimaging technique that utilizes near infrared light to measure cortical oxygenated and deoxygenated hemoglobin changes non-invasively. There were two groups, one group (n = 10) received only sham stimulation and the other group (n = 11) received sham followed by anodal stimulation to right ventral lateral prefrontal cortex. Results: Analyses revealed an increase in spatial memory performance following tDCS stimulation. This augmented performance was accompanied by changes to oxygenation (HbO-HbR) at the onset of the hemodynamic response in bilateral dorsolateral prefrontal cortex and left ventral medial prefrontal cortex. In these regions we also observed that stimulation improved neural processing efficiency, by reducing oxygenation and increasing performance from block to block. During and following tDCS stimulation, it was also observed that in bilateral dorsolateral prefrontal cortex the relationship between performance and oxygenation inverted, from a negative relationship to a positive relationship. Conclusion: The results suggest that tDCS is predominately a mechanism for changing neurons propensity for activity as opposed to their strength of activity. tDCS not only alters the efficiency of task relevant processing, but also the nature in which hemodynamic resources are used during augmented task performance.

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Anticipatory activity in rat medial prefrontal cortex during a working memory task.

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