Claustral Neurons Projecting to Frontal Cortex Mediate Contextual Association of Reward

The claustrum is a small nucleus, exhibiting vast reciprocal connectivity with cortical, subcortical, and midbrain regions. Recent studies, including ours, implicate the claustrum in salience detection and attention. In the current study, we develop an iterative functional investigation of the claustrum, guided by quantitative spatial transcriptional analysis. Using this approach, we identify a circuit involving dopamine-receptor expressing claustral neurons projecting to frontal cortex necessary for context association of reward. We describe the recruitment of claustral neurons by cocaine and their role in drug sensitization. In order to characterize the circuit within which these neurons are embedded, we apply chemo- and opto-genetic manipulation of increasingly specified claustral subpopulations. This strategy resolves the role of a defined network of claustrum neurons expressing dopamine D1 receptors and projecting to frontal cortex in the acquisition of cocaine conditioned-place preference and real-time optogenetic conditioned-place preference. In sum, our results suggest a role for a claustrum-to-frontal cortex circuit in the attribution of incentive salience, allocating attention to reward-related contextual cues.

[!abstract]+ The claustrum is a small nucleus, exhibiting vast reciprocal connectivity with cortical, subcortical, and midbrain regions. Recent studies, including ours, implicate the claustrum in salience detection and attention. In the current study, we develop an iterative functional investigation of the claustrum, guided by quantitative spatial transcriptional analysis. Using this approach, we identify a circuit involving dopamine-receptor expressing claustral neurons projecting to frontal cortex necessary for context association of reward. We describe the recruitment of claustral neurons by cocaine and their role in drug sensitization. In order to characterize the circuit within which these neurons are embedded, we apply chemo- and opto-genetic manipulation of increasingly speciﬁed claustral subpopulations. This strategy resolves the role of a deﬁned network of claustrum neurons expressing dopamine D1 receptors and projecting to frontal cortex in the acquisition of cocaine conditioned-place preference and real-time optogenetic conditioned-place preference. In sum, our results suggest a role for a claustrum-to-frontal cortex circuit in the attribution of incentive salience, allocating attention to reward-related contextual cues.

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(9.2.2024, 10:01:12 )

CLA reward: CLA projections to FC implicated in reward mechanisms via Dopamine

„Using this approach, we identify a circuit involving dopamine-receptor expressing claustral neurons projecting to frontal cortex necessary for context association of reward“ (Terem et al., 2020, p. 3522)

(Dopamine D1) „This strategy resolves the role of a defined network of claustrum neurons expressing dopamine D1 receptors and projecting to frontal cortex in the acquisition of cocaine conditioned-place preference and real-time optogenetic conditioned-place preference.“ (Terem et al., 2020, p. 3522)

„In sum, our results suggest a role for a claustrum-to-frontal cortex circuit in the attribution of incentive salience, allocating attention to reward-related contextual cues.“ (Terem et al., 2020, p. 3522)

„hypothesized to be involved in reward and reinforcement. In addition, the claustrum is recognized for its extensive neuromodulatory input. We find that inhibition of the activity of CLEgr2+ neurons attenuates behavioral sensitization to cocaine, providing the first functional association of the claustrum with cocaine-elicited behaviors.“ (Terem et al., 2020, p. 3528)

CLA salience: „These results implicate the claustrum in the encoding of cocaine experience and allude to a role of the claustrum in incentive salience“

(Terem et al., 2020, p. 3529)

„In contrast, the claustrum exhibits rich reciprocal connectivity with cortex, primarily frontal and association regions, an architecture more amenable to supporting ‘‘online’’ modulation of salience and attention.“ (Terem et al., 2020, p. 3529)

„Incentive salience is defined as the requirement for attentional resources to be allocated toward a salient context that is associated with a reward“ (Terem et al., 2020, p. 3529)

„The claustrum functions as a hub, associating subcortical neuromodulatory inputs and frontal cortical regions. The major projection of the claustrum extends to the ACC and OFC, frontal structures that are strongly associated with salience, attentional allocation, and drug reward [55–62]. Recent evidence implicates claustro-cortico-claustral networks in attention [3,4,13,38,40] and salience [12,15,16,63]. O“ (Terem et al., 2020, p. 3529)

promoting the development of a strong association between the reward and its context. The frontal projection of the claustrum has been reported to drive robust feedforward inhibition, dramatically shaping the activity pattern of frontal neurons“

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Claustral Neurons Projecting to Frontal Cortex Mediate Contextual Association of Reward