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The DNA shaping choices and actions.

A peculiar pattern of decision-making in mice, influenced by a specific gene called Arc, has been uncovered in a novel study.

During their search for food, mice would repeatedly visit an empty location instead of staying at a site abundant in food. However, a more practical approach was observed in mice that lacked the Arc gene, as they would stick to the food-rich site, resulting in an overall consumption of more calories.

This unique research potentially opens the door for a new field of study called ‘decision genetics’, which explores the genetic influence on decision-making, including possible implications for humans.


  • The influence of a specific gene called Arc on decision-making in mice has been revealed in a new study.
  • Mice lacking the Arc gene exhibited more rational foraging behavior, leading to a higher intake of calories.
  • The research suggests the emergence of a potential new field of study, known as ‘decision genetics’, which examines the genetic control over decision-making.

Have we ever made a decision that, in hindsight, seemed irrational? A new study with mice, which could have implications for us, suggests that some decisions are, to a certain extent, beyond our control. Instead, the mice are hard-wired to make them.

“This research is telling us that animals are constrained in the decisions they make,”

says Christopher Gregg, PhD, a neurobiologist at the University of Utah Health and senior author of the study recently published in iScience.

“Their genetics push them down one path or another.”

Gregg and the research team began investigating decision-making after noticing mice repeatedly making what appeared to be an irrational decision. After finding a stash of hidden seeds, instead of staying put to eat them, mice kept returning to a location that had food in it the day before. Only on that day, the original location was empty.


“It was as if the first location really had no food as if something had been missed.”

To Gregg and the study’s co-authors, the behavior didn’t make any sense. Less food was consumed by the animals due to the continuous return to the empty food patch. According to Gregg, if this kind of behavior causes mice to eat less in the wild, it could lead to trouble as insufficient calories can be detrimental to mice.

The real surprise came when it was discovered that the mice lacking a specific gene didn’t “second-guess” where to go and instead were more likely to stay and eat the food they found, resulting in an overall consumption of more calories.

This was the first evidence found by the scientists that decision-making could be biased by genes, even in decisions that didn’t appear logical, at least from a human perspective. In this case, the gene Arc seemed to play a significant role in compelling the mice to continue searching for food, even when it didn’t seem necessary.

“We all have a clear sense of what it is like to second-guess something, but who would have thought that this kind of behavior could be so profoundly influenced by one gene?”

says Stacher-Hörndli, a neurobiologist and co-author. “This raises the question: Are other cognitive biases under genetic control?”

Decoding behavior

From our perspective, a mouse’s life may appear fairly simple. When placed in a naturalistic setting in Gregg’s lab, their actions included leaving their home, exploring the surroundings, searching for food, eating a little, and making intermittent returns home. However, the perspective changed significantly when their journeys were deconstructed by a machine learning algorithm.

A custom program, developed by Gregg and co-author Jared Emery, analyzed 1,609 foraging excursions and identified 24 repeated behavior sequences in the mice. As the mice foraged, they connected these sequences together like building blocks, interspersing them with spontaneous behaviors to create more complex behavior patterns. One of these patterns involved second-guessing.

“To some extent, the future could be predicted,”

However, for mice lacking the Arc gene, the future changed. Six out of the 24 behavior sequences were altered, and collectively, these differences disrupted the second-guessing behavior. Previous research has indicated that Arc is involved in learning and memory.

Nevertheless, the overall analysis demonstrated that the mice’s memory and other behaviors were mostly unaffected. This implies that the impact was specific to those six behaviors.

“One intriguing idea is that the decisions were evolved by the animals because they had some advantage in the wild,”  – says Gregg.

He explains one possibility: when mice evaluate previous food locations by going back and forth, it assists in the creation of a mental map. This, in turn, may help them locate food more quickly in subsequent instances. “The presence of genetically controlled cognitive bias may enable effective decision-making during foraging,” he says.

The question that remains is whether there is a biological basis for other forms of cognitive bias. And could decision-making in humans be guided by genes? Further research will provide answers.

“I believe that this research lays the foundation for a new field that we refer to as ‘decision genetics’,” says Stacher-Hörndli.


Arc Regulates a Second-Guessing Cognitive Bias During Naturalistic Foraging Through Effects on Discrete Behavior Modules

Second-guessing is an economically irrational cognitive bias in foraging mice
Loss of the synaptic plasticity gene, Arc, specifically affects second-guessing
Machine learning decompositions of foraging reveal Arc-controlled behaviors
Linkage of cognitive decision bias, genetic factors, and behavioral modularity


Foraging in animals relies on innate decision-making heuristics that can result in suboptimal cognitive biases in some contexts. The mechanisms underlying these biases are not well understood, but likely involve strong genetic effects.

To explore this, we studied fasted mice using a naturalistic foraging paradigm and discovered an innate cognitive bias called “second-guessing.” This involves repeatedly investigating an empty former food patch instead of consuming available food, which hinders the mice from maximizing feeding benefits.

The synaptic plasticity gene Arc is revealed to play a role in this bias, as Arc-deficient mice did not exhibit second-guessing and consumed more food. In addition, unsupervised machine learning decompositions of foraging identified specific behavior sequences, or “modules”, that are affected by Arc.

These findings highlight the genetic basis of cognitive biases in decision making, show links between behavior modules and cognitive bias, and provide insight into the ethological roles of Arc in naturalistic foraging.

Arc Regulates a Second-Guessing Cognitive Bias During Naturalistic Foraging Through Effects on Discrete Behavior Modules” by Christopher Gregg et al. Science