4.8 Article

FosGFP expression does not capture a sensory learning-related engram in superficial layers of mouse barrel cortex

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NATL ACAD SCIENCES
DOI: 10.1073/pnas.2112212118

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c-fos; engram; learning; plasticity; barrel cortex

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The expression of immediate-early genes (IEGs) has been utilized to pinpoint small neural ensembles associated with specific experiences, however, in whisker-dependent sensory association learning, the training effect on IEG-marked neurons is not detectable. Synaptic strengthening in response to training is concentrated in non-IEG marked neurons in the primary somatosensory cortex.
Immediate-early gene (IEG) expression has been used to identify small neural ensembles linked to a particular experience, based on the principle that a selective subset of activated neurons will encode specific memories or behavioral responses. The majority of these studies have focused on engrams in higher-order brain areas where more abstract or convergent sensory information is represented, such as the hippocampus, prefrontal cortex, or amygdala. In primary sensory cortex, IEG expression can label neurons that are responsive to specific sensory stimuli, but experience dependent shaping of neural ensembles marked by IEG expression has not been demonstrated. Here, we use a fosGFP transgenic mouse to longitudinally monitor in vivo expression of the activity dependent gene c-fos in superficial layers (L2/3) of primary somatosensory cortex (S1) during a whisker-dependent learning task. We find that sensory association training does not detectably alter fosGFP expression in L2/3 neurons. Although training broadly enhances thalamocortical synaptic strength in pyramidal neurons, we find that synapses onto fosGFP+ neurons are not selectively increased by training; rather, synaptic strengthening is concentrated in fosGFP2 neurons. Taken together, these data indicate that expression of the IEG reporter fosGFP does not facilitate identification of a learning-specific engram in L2/3 in barrel cortex during whisker-dependent sensory association learning.

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