The Role of Neuroligin-1 in Learning and Motivation

TL;DR: Researchers investigated the role of the protein Neuroligin-1 in learning and motivation by deactivating the Neuroligin-1 gene in a group of mice. They found that although the mice’s ability to learn remained intact, they were less motivated to work for a reward and more motivated to work to escape a negative situation. These findings help explain the role of Neuroligin-1 in decision-making and show that learning and motivation, two closely related aspects of behavior, are controlled by different cellular mechanisms.

Key Terms

• Neuroligin-1: A synaptic, cell-adhesion protein involved in the formation and

maintenance of synapses between neurons.

• N-Methyl-D-aspartate (NMDA) receptor: A receptor that binds to the neurotransmitter

glutamate, allowing the entry of calcium ions into cells for cellular processes such as

synaptic plasticity.

• Long-term potentiation: A type of synaptic plasticity characterized by a long-lasting

increase in the strength of synaptic transmission between neurons.

Background

Previous research has focused on studying the role of Neuroligin-1 in cells and has provided

evidence that Neuroligin-1 is important for the activity of NMDA receptors and for long-term

potentiation, two mechanisms thought to play a vital role in learning and memory. However,

research on the role of Neuroligin-1 in complex behavioral tasks, such as decision-making, is

limited. Hence, it is unclear if the effects of an absence of Neuroligin-1 apply to all types of

learning, and further research could help clarify the role of Neuroligin-1 in cognitive function.

Methods

Two groups of mice were used: an experimental group in which the Neuroligin-1 gene was

deactivated, and a control group in which the gene remained intact. The mice completed

several cognitive touchscreen tests under different testing conditions. The mice were shown

images on a touchscreen and had to respond, via a nose-poke, to the correct image to earn

a strawberry milk reward. Multiple measures were taken, depending on the testing condition:

• Performance accuracy: % of correct responses until a learning criterion was reached.

• Rate of reversal learning: How quickly the mouse changes its response when the

image that results in the reward is reversed.

• Rate of extinction learning: How quickly the mouse stops performing the learned

response when nose-poking the image no longer results in the reward.

• Initiation latency: Time taken for the mouse to initiate the trial.

• Stimulus-approach latency: Time taken for the mouse to reach the touchscreen after

initiating the trial.

• Stimulus-selection latency: Time taken for the mouse to nose-poke an image after

reaching the touchscreen.

• Reward collection latency: Time taken for a mouse to collect the reward after nose-

poking the image.

• Number of responses performed as the response requirement for a reward increases

(e.g., from 1 to 5 nose-pokes to obtain the reward).

The two groups then participated in the Porsolt swim test, in which the mice were placed in a

container of water. The time the mice spent swimming or attempting to escape the negative

situation of being immersed in water, rather than remaining relatively still, was measured.

Results

• There were no significant differences in the performance accuracy, rates of reversal

learning, and rates of extinction learning between the two groups, indicating that the

absence of Neuroligin-1 did not affect the mice’s ability to learn.

• Although the mice without Neuroligin-1 did not take longer to nose-poke an image,

they did take longer to initiate the trial, approach the touchscreen, and collect the

reward, indicating that the absence of Neuroligin-1 decreased the mice’s motivation

to obtain the reward.

• Similarly, when more nose-pokes were required to earn the strawberry milk reward

(higher response requirements), the mice without Neuroligin-1 performed fewer

responses.

• In the Porsolt swim test, mice without Neuroligin-1 spent more time swimming or

attempting to escape, indicating an increased motivation to escape the negative

situation.

Conclusion

Decision-making requires the ability to learn which actions result in positive and negative

outcomes and to weigh the value or ‘reward’ of achieving a positive outcome or avoiding a

negative one against the effort or ‘cost’ required to do so. This study suggests that reduced

NMDA receptor activity and decreased long-term potentiation caused by the absence of

Neuroligin-1 may not always lead to impaired learning. Additionally, these findings suggest

that Neuroligin-1 is involved in reward-cost trade-offs, the process of weighing the benefits of

a decision against its drawbacks; for example, the benefit of obtaining the strawberry milk

reward against the cost of repeatedly nose-poking the image to earn it. Specifically,

Neuroligin-1 may influence the motivation to pursue positive outcomes or avoid negative

ones.

References

The original research paper can be found at: Springer Nature Article Link.

This paper was simplified by Ethan Malunga.