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    Home > Active Ingredient News > Study of Nervous System > Cell | Prefrontal deep projection neurons are monitored through continuous feedback to achieve cognitive flexibility

    Cell | Prefrontal deep projection neurons are monitored through continuous feedback to achieve cognitive flexibility

    • Last Update: 2021-05-09
    • Source: Internet
    • Author: User
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    Written | Qi Cognitive flexibility, that is, the ability to change strategies based on changing stimulus-response-reward relationships, is considered to be the key to renewing learning behavior.

    In clinical practice, attentional set-shifting tests are often used to assess cognitive flexibility (that is, subjects are asked to ignore previously related stimulus features and replace them with previously unrelated features) [1].

    In a series of mental diseases, the phenomenon of impaired set transfer ability is very common and usually persists after treatment of depression and schizophrenia [2].

    Previous studies have shown that the prefrontal cortex (PFC) plays a key role in supporting the fixed transfer behavior of human and rodent models [3, 4], but the specific mechanism is still unclear.

    In recent years, a major issue in behavioral neuroscience has focused on how to best define the anatomical markers of cell types in the cortex.

    The key effect of PFC activity on fixed transfer may be mediated by many efferent pathways, two of which are particularly attractive targets are the ventromedial striatum (PFC-VMS) and the medial thalamus (PFC-MDT).
    It has been proved in rodent models that both projections play an important role in set transfer behavior [5].

    However, whether these two projections convey similar or different mission-critical information remains unclear.

    On April 15, 2021, the Conor Liston team from Weill Cornell Medical College in the United States published an article titled "Prefrontal deep projection neurons enable cognitive flexibility via persistent feedback monitoring" in Cell magazine.

    This study develops and validates a new type of set transfer test that can enable two-photon imaging in head-fixed mice, revealing that projection neurons in the deep prefrontal cortex are supporting set transfer by transmitting feedback information to downstream target cells.
    Play a key role in the

    First, in each experiment, water-limited mice were randomly combined to present one of two possible vibrating tentacles (for example, bilateral vibration of 35 Hz vs.
    155 Hz) and one of two possible odor stimuli.
    For example, almond oil versus olive oil, when the 2.
    5s complex stimulation is terminated, the water reward is obtained by licking the left or right mouth, prompting the mice to respond (see Figure 1).

    In order to test the task-related activities of PFC neurons, the author performed GCaMP6f-mediated two-photon calcium imaging through the implanted microprism.
    The results showed that all task elements required to successfully perform the task are manifested in the activity of the PFC neuron group, and the response is related The activity patterns and the outcome-related activity patterns are more relevant than the activity patterns related to decision-related stimuli, and the response-related patterns lag behind rather than guide the animal’s behavioral choices.

    Figure 1.
    Schematic diagram of a series of fixed transfer tasks in the prefrontal lobe of mice.
    In addition, the authors found that PFC cells are highly heterogeneous in their contribution to cognitive flexibility.

    In order to study the contribution of the projection target specificity to the functional heterogeneity of PFC neurons during fixed transfer, the authors tested the PFC-VMS and PFC-MDT two sets of projection neurons that have been reported in previous work to support cognitive flexibility.
    The functional characteristics.

    Unexpectedly, these two groups of neurons showed amazing overall similarity in the task response of mice, suggesting that although a single PFC neuron is highly heterogeneous in functional characteristics, the efferent projection target cannot explain this.
    Functional heterogeneity of the two main projection subtypes.

    The similarity of PFC-VMS and PFC-MDT makes the question of whether the functional heterogeneity of PFC neurons can be explained by their spatial distribution is still unanswered.

    Previous work has demonstrated that the temporal correlation between pairs of neurons recorded simultaneously in the sensory cortex decays with increasing distance, which indicates that there is a correlation between spatial proximity and temporal coordinated activation.

    In order to evaluate whether the neuron's responsiveness to the test changes with the distance from the meningeal surface, the authors further quantified the overall variance of the average waveform of the test to capture the intensity of the neuronal response, including the excited and inhibited neurons at each time point The intensity of the response, and then found that the deeper neurons (further from the surface of the cortex) show a greater response amplitude.

    Furthermore, the author solved the problem of whether the deep and superficial neurons have different afferent sources by using the rabies virus tracing method, and found that from the anterior cingulate cortex (ACC) of the ventral side of the tail to the deep PFC projection neurons The rich input of may drive the stronger performance of experimental feedback-related information observed in deep neurons.

    In general, this study uses optogenetics and two-photon calcium imaging technology to prove that PFC activity does not affect the sensorimotor response during set transfer, but instead encodes experimental feedback to achieve set transfer.
    And the functional characteristics of PFC cells did not change with the change of its outgoing projection target.

    On the contrary, the characterization of experimental feedback forms a topological gradient, and cells located farther away from the surface of the pia mater are more selective for feedback information, confirming the key to deep PFC projection neurons in realizing set transfer through behavioral feedback monitoring.

    Of course, it is still necessary to clarify the underlying neuromodulation and plasticity-related mechanisms behind these signals in the future.

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    Plate maker: Qijiang Reference 1.
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    Murphy, FC, Michael, A.
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    Emotion modulates cognitive flexibility in patients with major depression.
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    Kim, C.
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    Domain general and domain preferential brain regions associated with different types of task switching: a meta-analysis.
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    irrell, JM, and Brown, VJ (2000).
    Medial frontal cortex mediates perceptual attentional set shifting in the rat.
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