Summary: Researchers are narrowing in on how cognitive flexibility and adult neurogenesis are linked. Using a newly developed mouse model that increases the complexity of a standard maze task, the team discovered that gamma radiation selectively impairs cognitive adaptability while specific cohorts of adult-born hippocampal neurons respond distinctly to the task. The findings reinforce a tight connection between hippocampal neurogenesis, aging, and the ability to adjust strategies when conditions change.
Key Facts:
- The researchers designed an advanced Morris water maze variant that forces mice to adapt to changing contextual cues and platform locations.
- Gamma-radiation exposure reduced cognitive flexibility—mice continued searching the platform’s previous location—without preventing initial task learning.
- Aging reduced neurogenesis and cognitive adaptability in parallel, suggesting hippocampal neurogenesis as a potential target for interventions to restore flexible cognition.
Source: Stony Brook University
Cognitive flexibility—the ability to shift problem-solving strategies when circumstances change—is essential for adapting to new situations. When this capacity declines because of aging, disease, injury, or environmental exposures, behavior becomes rigid and individuals struggle to modify previously learned responses.
The same factors that impair cognitive flexibility also reduce the generation of new neurons in the adult brain, a process called adult neurogenesis. However, how these two phenomena relate has been unclear. A team led by Grigori Enikolopov, Ph.D., at Stony Brook University developed a refined behavioral model to probe the relationship between hippocampal neurogenesis and the capacity to adjust learned strategies.
Their results are presented in two papers published in Journal of Neuroscience and Frontiers in Neuroscience. According to Enikolopov, scientific progress has been limited by a lack of sensitive models that reveal how specific cognitive abilities are affected by different challenges. To address this, the team designed a complex version of the Morris water maze that requires animals to integrate multiple contextual cues and to revise learned search strategies.
The classic Morris water maze asks a mouse to locate a submerged platform using spatial cues on the maze walls. The new assay increases task demands by altering variables such as the pool’s color, adding conspicuous local cues (for example, toys suspended above the water), and periodically changing the platform’s position. These manipulations force mice to rely on flexible strategy selection rather than a fixed cue-location association.
In the Journal of Neuroscience study, the team explored the effects of γ-radiation on cognitive flexibility and hippocampal neurogenesis. Mice exposed to radiation were able to learn the standard spatial task but showed reduced flexibility when faced with the more demanding, context-discrimination version of the maze: they persisted in searching the platform’s prior location rather than adapting to the changed cues.
Evgeny Amelchenko, Ph.D., the first author, reports that adult-born neurons recruited by the complex task were selectively those that had matured approximately three months earlier. Younger adult-born neurons did not show the same activation pattern, suggesting that the functional contribution of new neurons depends on their age at the time of learning.
Because aging commonly degrades both cognitive flexibility and neurogenesis, the researchers compared 6-month-old (mature adult) and 14-month-old (late middle-age) mice on the complex maze task, findings they describe in Frontiers in Neuroscience. Both age groups succeeded on the simple spatial version, but older mice performed worse on the reversal and context-discrimination versions that required reassessment and strategy changes.
Importantly, the degree of impairment correlated with individual levels of hippocampal neurogenesis: mice that had fewer adult-born neurons weeks or months prior to testing were less effective at adjusting their search strategies. The older animals did improve with additional training, narrowing the performance gap, which indicates some retained capacity for adaptation despite age-related decline.
Taken together, the two studies highlight a selective role for hippocampal neurogenesis in supporting cognitive flexibility rather than basic spatial learning and memory. Both radiation exposure and natural aging reduced neurogenesis, delayed adaptive learning, and favored inefficient, habitual navigation strategies when task demands required strategy shifts.
The authors propose that boosting hippocampal neurogenesis may be a promising avenue to restore flexible cognition in aging or after damaging exposures. Future work will examine how groups of neurons born at different times contribute to flexible behavior and whether this behavioral assay can screen compounds that enhance cognitive adaptability. The team also aims to translate these findings to humans using functional imaging to better understand how aging and disease compromise the brain’s ability to reconfigure behavior.
About this cognitive flexibility and neurogenesis research news
Author: Grigori Enikolopov
Source: Stony Brook University
Contact: Grigori Enikolopov – Stony Brook University
Image: The image is credited to Neuroscience News
Original Research: Open access.
“Age-related decline in cognitive flexibility is associated with the levels of hippocampal neurogenesis” by Evgeny M. Amelchenko et al. Frontiers in Neuroscience
Closed access.
“Cognitive Flexibility Is Selectively Impaired by Radiation and Is Associated with Differential Recruitment of Adult-Born Neurons” by Evgeny M. Amelchenko et al. Journal of Neuroscience
Abstract
Age-related decline in cognitive flexibility is associated with the levels of hippocampal neurogenesis
Aging brings declines in learning, memory, and cognitive flexibility alongside a gradual reduction in hippocampal neurogenesis. We tested 6- and 14-month-old mice on standard and modified Morris water maze tasks and quantified neurogenesis measured weeks to months prior to testing. Although both age groups learned the basic spatial task, older mice were less efficient on reversal and context-discrimination tasks that required updating prior strategies. Older mice showed improvement with additional training. Across individuals, levels of adult-born neurons correlated with performance in tasks demanding cognitive flexibility, underscoring the role of hippocampal neurogenesis in adaptive behavior.
Abstract
Cognitive Flexibility Is Selectively Impaired by Radiation and Is Associated with Differential Recruitment of Adult-Born Neurons
Exposure to elevated doses of ionizing radiation increases the risk of cognitive dysfunction, but the full behavioral impact can be missed by standard tests. We developed a context-discrimination Morris water maze (cdMWM) that requires integration of contextual cues and strategy adjustment. Male mice exposed to 1 or 5 Gy of γ rays were tested on spatial, reversal, and context-discrimination versions at multiple time points after irradiation. Mice receiving 5 Gy performed the simple spatial and reversal tasks but showed transient deficits in the cdMWM 6–8 weeks after irradiation, including reduced use of efficient spatial search strategies and memory impairment at 6 weeks. Irradiation impaired neurogenesis and altered the recruitment of 12-week-old adult-born neurons by specific task components. These results reveal radiation effects on cognitive flexibility and suggest an extended maturation period for functionally relevant newborn hippocampal neurons.