Activation, but not inhibition, of the indirect pathway disrupts choice rejection in a freely moving, multiple-choice foraging task

Delevich, Kristen; Hoshal, Benjamin; Zhou, Lexi Z.; Zhang, Yuting; Vedula, Satya; Lin, Wan Chen; Chase, Juliana; Collins, Anne; Wilbrecht, Linda

doi:10.1016/j.celrep.2022.111129

Cited by 6 publications

(2 citation statements)

References 56 publications

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“…As we could disentangle reward saturation from sensitivity to uncertainty in our multiple-choice setup, our results extend and explains the ones obtained in tasks involving binary choices. For instance, activating iSPNs may increase seemingly stochastic choices in serial choices in which the exploratory choice may also constitute a risky (high variance) choice 81 because reward saturation affects the perception of risk (Figure 4 and Supp. Figure 4).…”

Section: Discussionmentioning

confidence: 99%

Direct and indirect striatal projecting neurons exert strategy-dependent effects on decision-making

Rodriguez,

Naudé,

Rial

et al. 2024

Preprint

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Striatum constitutes one of the key nodes of the decision-making circuit, with differing roles depending on the striatal localization and both direct and indirect pathway Striatal Projecting Neurons (d- and i-SPNs) populations. In a gambling task adapted to mice, we leveraged a computational characterization of the diversity in cognitive profiles to delve further into the striatal roles in decision-making. Individual decision-making profiles could be described as a combination between archetypal strategies (Optimizers, Risk-averse, Explorers). Such strategies reflected stable differences in the parameters generating decisions (sensitivity to reward magnitude, to risk or to punishment) derived from a reinforcement-learning fit of animal choices. Using a chemogenetic method, we found that dorsomedial striatum (DMS) neurons had the most significant impact on decision-making, while Nucleus accumbens (NAc) had a minor effect and dorsolateral striatum (DLS) had none. Specifically, d- SPNs reduce risk aversion by enhancing the perceived value of a risky choice in mice. On the other hand, i-SPNs amplified the importance of large gains, exerting opposite effects on mice depending on their decision-making profiles. Hence, we propose that striatal manipulations exert profile-dependent effects on choices because striatal subpopulations affect distinct parameters that interact to generate decisions.

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Section: Discussionmentioning

confidence: 99%

Direct and indirect striatal projecting neurons exert strategy-dependent effects on decision-making

Rodriguez,

Naudé,

Rial

et al. 2024

Preprint

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show abstract

“…However, in the reversal stage of the task, Cntnap2 -/- mice took significantly more trials to learn a new odor- reward pairing, owing primarily to continued choice of the previously rewarded odor. The DMS and ventral striatum (nucleus accumbens) have been shown to play an important role in reversal learning (Izquierdo et al, 2017), and in the four choice task specifically (Delevich et al, 2022). Additionally, decreased dopamine release in the DLS is associated with deficits in reversal learning in this task (Kosillo et al, 2019; Lin et al, 2022).…”

Section: Discussionmentioning

confidence: 99%

Cntnap2loss drives striatal neuron hyperexcitability and behavioral inflexibility

Cording,

Tu,

Wang

et al. 2024

Preprint

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Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by two major diagnostic criteria - persistent deficits in social communication and interaction, and the presence of restricted, repetitive patterns of behavior (RRBs). Evidence from both human and animal model studies of ASD suggest that alteration of striatal circuits, which mediate motor learning, action selection, and habit formation, may contribute to the manifestation of RRBs. CNTNAP2 is a syndromic ASD risk gene, and loss of function of Cntnap2 in mice is associated with RRBs. How loss of Cntnap2 impacts striatal neuron function is largely unknown. In this study, we utilized Cntnap2-/- mice to test whether altered striatal neuron activity contributes to aberrant motor behaviors relevant to ASD. We find that Cntnap2-/- mice exhibit increased cortical drive of striatal projection neurons (SPNs), with the most pronounced effects in direct pathway SPNs. This enhanced drive is likely due to increased intrinsic excitability of SPNs, which make them more responsive to cortical inputs. We also find that Cntnap2-/- mice exhibit spontaneous repetitive behaviors, increased motor routine learning, and cognitive inflexibility. Increased corticostriatal drive, in particular of the direct pathway, may contribute to the acquisition of repetitive, inflexible behaviors in Cntnap2 mice.

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Understanding patch foraging strategies across development

Lloyd¹,

Viding²,

McKay³

et al. 2023

Trends in Cognitive Sciences

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Activation, but not inhibition, of the indirect pathway disrupts choice rejection in a freely moving, multiple-choice foraging task

Cited by 6 publications

References 56 publications

Direct and indirect striatal projecting neurons exert strategy-dependent effects on decision-making

Direct and indirect striatal projecting neurons exert strategy-dependent effects on decision-making

Cntnap2loss drives striatal neuron hyperexcitability and behavioral inflexibility

Understanding patch foraging strategies across development

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