The frontal cortex, especially the anterior cingulate cortex area (ACA), is essential for exerting cognitive control after errors, but the mechanisms that enable modulation of attention to improve ...performance after errors are poorly understood. Here we demonstrate that during a mouse visual attention task, ACA neurons projecting to the visual cortex (VIS; ACAVIS neurons) are recruited selectively by recent errors. Optogenetic manipulations of this pathway collectively support the model that rhythmic modulation of ACAVIS neurons in anticipation of visual stimuli is crucial for adjusting performance following errors. 30-Hz optogenetic stimulation of ACAVIS neurons in anesthetized mice recapitulates the increased gamma and reduced theta VIS oscillatory changes that are associated with endogenous post-error performance during behavior and subsequently increased visually evoked spiking, a hallmark feature of visual attention. This frontal sensory neural circuit links error monitoring with implementing adjustments of attention to guide behavioral adaptation, pointing to a circuit-based mechanism for promoting cognitive control.
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•Top-down frontal sensory projections are selectively recruited after error trials•30-Hz optogenetic stimulation of top-down neurons promotes post-error performance•Post-error performance adjustment requires anticipatory top-down activity•30-Hz optogenetic top-down stimulation promotes a hallmark feature of attention
Norman et. al found that behavioral errors recruit frontal sensory projections in mice. 30-Hz optogenetic stimulation of this pathway modulates performance following errors in behaving mice and recapitulates neurophysiological hallmarks of attention in anesthetized mice. Frontal sensory projections therefore link error monitoring with attention adjustments for behavioral adaptation.
Aim
Attention is a goal‐directed cognitive process that facilitates the detection of task‐relevant sensory stimuli from dynamic environments. Anterior cingulate cortical area (ACA) is known to play a ...key role in attentional behavior, but the specific circuits mediating attention remain largely unknown. As ACA modulates sensory processing in the visual cortex (VIS), we aim to test a hypothesis that frontal top‐down neurons projecting from ACA to VIS (ACAVIS) contributes to visual attention behavior through chemogenetic approach.
Methods
Adult, male mice were trained to perform the 5‐choice serial reaction time task (5CSRTT) using a touchscreen system. An intersectional viral approach was used to selectively express inhibitory designer receptors exclusively activated by designer drugs (iDREADD) or a static fluorophore (mCherry) in ACAVIS neurons. Mice received counterbalanced injections (i.p.) of the iDREADD ligand (clozapine‐N‐oxide; CNO) or vehicle (saline) prior to 5CSRTT testing. Finally, mice underwent progressive ratio testing and open field testing following CNO or saline administration.
Results
Chemogenetic suppression of ACAVIS neuron activity decreased correct task performance during the 5CSRTT mainly driven by an increase in omission and a trending decrease in accuracy with no change in behavioral outcomes associated with motivation, impulsivity, or compulsivity. Breakpoint during the progressive ratio task and distance moved in the open field test were unaffected by ACAVIS neuron suppression. CNO administration itself had no effect on task performance in mCherry‐expressing mice.
Conclusion
These results identify long‐range frontal‐sensory ACAVIS projection neurons as a key enactor of top‐down attentional behavior and may serve as a beneficial therapeutic target.
Circuit‐specific chemogenetic silencing demonstrated that frontal neurons projecting from anterior cingulate cortex to visual are essential for top‐down control of attention behavior in mice. This study suggests that long‐range frontal‐sensory projection neurons as a key enactor of top‐down attentional behavior and may serve as a beneficial therapeutic target.
Cognitive function depends on frontal cortex development; however, the mechanisms driving this process are poorly understood. Here, we identify that dynamic regulation of the nicotinic cholinergic ...system is a key driver of attentional circuit maturation associated with top-down frontal neurons projecting to visual cortex. The top-down neurons receive robust cholinergic inputs, but their nicotinic tone decreases following adolescence by increasing expression of a nicotinic brake,
shifts a balance between local and long-range inputs onto top-down frontal neurons following adolescence and promotes the establishment of attentional behavior in adulthood. This key maturational process is disrupted in a mouse model of fragile X syndrome but was rescued by a suppression of nicotinic tone through the introduction of
in top-down projections. Nicotinic signaling may serve as a target to rebalance local/long-range balance and treat cognitive deficits in neurodevelopmental disorders.
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