A molecular insight into the dissociable regulation of associative learning and motivation by the synaptic protein neuro
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RESEARCH ARTICLE
Open Access
A molecular insight into the dissociable regulation of associative learning and motivation by the synaptic protein neuroligin-1 Jiaqi Luo, Jessica M. Tan and Jess Nithianantharajah*
Abstract Background: In a changing environment, a challenge for the brain is to flexibly guide adaptive behavior towards survival. Complex behavior and the underlying neural computations emerge from the structural components of the brain across many levels: circuits, cells, and ultimately the signaling complex of proteins at synapses. In line with this logic, dynamic modification of synaptic strength or synaptic plasticity is widely considered the cellular level implementation for adaptive behavior such as learning and memory. Predominantly expressed at excitatory synapses, the postsynaptic cell-adhesion molecule neuroligin-1 (Nlgn1) forms trans-synaptic complexes with presynaptic neurexins. Extensive evidence supports that Nlgn1 is essential for NMDA receptor transmission and long-term potentiation (LTP), both of which are putative synaptic mechanisms underlying learning and memory. Here, employing a comprehensive battery of touchscreen-based cognitive assays, we asked whether impaired NMDA receptor transmission and LTP in mice lacking Nlgn1 does in fact disrupt decision-making. To this end, we addressed two key decision problems: (i) the ability to learn and exploit the associative structure of the environment and (ii) balancing the trade-off between potential rewards and costs, or positive and negative utilities of available actions. Results: We found that the capacity to acquire complex associative structures and adjust learned associations was intact. However, loss of Nlgn1 alters motivation leading to a reduced willingness to overcome effort cost for reward and an increased willingness to exert effort to escape an aversive situation. We suggest Nlgn1 may be important for balancing the weighting on positive and negative utilities in reward-cost trade-off. Conclusions: Our findings update canonical views of this key synaptic molecule in behavior and suggest Nlgn1 may be essential for regulating distinct cognitive processes underlying action selection. Our data demonstrate that learning and motivational computations can be dissociated within the same animal model, from a detailed behavioral dissection. Further, these results highlight the complexities in mapping synaptic mechanisms to their behavioral consequences, and the future challenge to elucidate how complex behavior emerges through different levels of neural hardware. Keywords: Cost-benefit trade-off, Learning and memory, Motivation, NL1, Response latency, Response vigor, Rodent touchscreens
* Correspondence: [email protected] Florey Institute of Neuroscience and Mental Health, Florey Department of Neuroscience, Melbourne Brain Centre, University of Melbourne, 30 Royal Parade, Parkville, Victoria 3052, Australia © The Author(s). 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which pe
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