Chemogenetics reveal an anterior cingulate-thalamic pathway for attending to task-relevant information

Abstract

In a changing environment, we need to decide when to select items that resemble previously rewarded stimuli and when it is best to switch to other stimulus types. Here, we used chemogenetic techniques to provide causal evidence that activity in the rodent anterior cingulate cortex and its efferents to the anterior thalamic nuclei modulate the ability to attend to reliable predictors of important outcomes. Rats were tested on an attentional set-shifting paradigm that first measures the ability to master serial discriminations involving a constant stimulus dimension that reliably predicts reinforcement (intradimensional-shift), followed by the ability to shift attention to a previously irrelevant class of stimuli when reinforcement contingencies change (extradimensional-shift).Chemogenetic silencing of the anterior cingulate cortex (Experiment 1) as well as selective inactivation of anterior cingulate efferents to the anterior thalamic nuclei (Experiment 2) impaired intradimensional learning but, facilitated two sets of extradimensional-shifts. This pattern of results signals the loss of a cortico-thalamic system for cognitive control that preferentially processes stimuli resembling those previously associated with reward.Previous studies highlight a separate prefrontal system that promotes switching to hitherto inconsistent predictors of reward when contingencies change. Competition between these two systems regulates cognitive flexibility and choice.

The anterior thalamic nuclei and cognition: A role beyond space?

“…Perhaps of particular note are its dense connections with frontal areas suggesting that the anteromedial nucleus may serves as a site of integration between frontal areas and the hippocampus to modulate attentional and cognitive control processes that underpin mnemonic functions. The recent evidence that inhibiting information flow from the anterior cingulate cortex to the anteromedial thalamus is sufficient to disrupt attention to task-relevant information is consistent with this proposition ( Bubb et al, 2020 ). At the same time, anteromedial interconnections with the lateral entorhinal and perirhinal cortices, sites important for object information, suggest that the anteromedial nucleus may similarly act as an interface between frontal and hippocampal/parahippocampal areas that contribute to recency memory and other forms of associative recognition memory.…”

“…Given that this profile of performance is diametrically opposed to the effects of prefrontal damage on this task ( Birrell et al, 2000 ), this raises the question of which sites do the anterior thalamic nuclei interact to support these attentional mechanisms. Subsequent work has shown that chemogenetic inhibition of the anterior cingulate cortex reproduces exactly the effects of anterior thalamic nuclei lesions on this task i.e ., impaired attentional set-formation but facilitated extradimensional set-shifting ( Bubb et al, 2020 ). Further work using DREADDs to selectively disrupt anterior cingulate terminals in the anteroventral and anteromedial thalamic nuclei has confirmed that interactions between these two sites are required for animals to attend to reliable predictors of reinforcement ( Bubb et al, 2020 ).…”

“…Subsequent work has shown that chemogenetic inhibition of the anterior cingulate cortex reproduces exactly the effects of anterior thalamic nuclei lesions on this task i.e ., impaired attentional set-formation but facilitated extradimensional set-shifting ( Bubb et al, 2020 ). Further work using DREADDs to selectively disrupt anterior cingulate terminals in the anteroventral and anteromedial thalamic nuclei has confirmed that interactions between these two sites are required for animals to attend to reliable predictors of reinforcement ( Bubb et al, 2020 ). Taken together these findings not only reveal that the anterior thalamic nuclei have vital attentional functions, but they also highlight the importance of their interconnections with sites beyond Papez circuit.…”

The anterior cingulate cortex directly enhances auditory cortical responses in air-puffing-facilitated flight behavior

“…The ACC participates in many advanced functions, such as attention, motivation, anticipation, and emotion (Bush et al, 2000;Hughes and Beer, 2012;Pardo et al, 1990;Sohn et al, 2007). Also, the ACC can modulate the visual cortex (Zhang et al, 2014), claustrum (White et al, 2018), and thalamus (Bubb et al, 2021). Hence, the ACC helps determine relevant task performance by participating in the top-down control of these areas.…”

Neurofisiologia da predição baseada em memórias sobre regularidades passadas

“…Although it seems clear that the structures composing the "extended hippocampal system" play a critical role in spatial learning and declarative memory, one should not ignore evidence that they are not restricted only to this role (e.g., Carlesimo et al, 2015;Wolff et al, 2015). For example, it has been shown that these structures participate in attentional set-shifting (Wright et al, 2015;Bubb et al, 2021), contextual fear memory (Dupire et al, 2013;Marchand et al, 2014) and fear conditioning promoted by predator threats (Carvalho-Netto et al, 2010;De Lima, Baldo & Canteras, 2017).…”