Researchers from The University of Queensland (UQ) and the Australian National University (ANU) have identified a brain circuit linked to the flexible formation of memories that may help explain some of the differences in learning associated with autism spectrum disorder.
While characteristics like social communication and repetitive behaviours are often emphasised in autism research, differences in learning and memory associated with autism spectrum disorder remain far less understood.
As part of their ongoing studies into the neurobiology of autism, Associate Professor Nathalie Dehorter and her research teams at UQ's Queensland Brain Institute and the ANU identified that a specific brain structure, the dorsal CA1 (dCA1) region of the hippocampus, plays a pivotal role in explicit memory in autism.
"This type of memory, often referred to as explicit or declarative memory, involves the conscious recollection of facts, past experiences and concepts, and it requires flexibility to relate and manipulate that information," Associate Professor Dehorter explained.
"Many everyday memories require our brains to bridge gaps between events, such as remembering that a conversation led to a decision later in the day.
“We wanted to investigate the brain's ability to form memories linking two events separated by short or long intervals, in a well-established mouse model of autism."
Postdoctoral Fellow Dr Shaam Al Abed said the study addresses a knowledge gap that has limited the development of clinical approaches.
“Our findings highlight the dCA1 region as a potential therapeutic target for addressing memory impairments and reduced cognitive flexibility, both of which have been reported in some people with autism spectrum disorder,” Dr Al Abed said.
The team found that the mouse model of autism had decreased dCA1 activity during the critical time gap between events.
Importantly, restoring hippocampal activity during that time window also restored the mice's ability to form the memory, pointing to a promising avenue for further research.
The study also found that both the mice modelling autism and control mice could learn associations separated by short delays, but the affected mouse showed difficulties once the time interval increased.
"Although they successfully learned the task, these mice were less able to retain the memory 24 hours later," Dr Al Abed said.
"These results point to a difference in temporal binding: the brain's ability to connect events that occur at different times into a single, coherent memory."
A Rigid Route to Spatial Learning
In collaboration with Professor Marighetto's team at the Neurocentre Magendie, France, the team's second discovery relates to differences in learning strategies.
Mapping brain activity revealed reduced activation of hippocampal regions in the affected mouse, alongside increased use of striatal circuits, the brain's selection and coordination system.
This pattern is consistent with an inability to properly use spatial cues to navigate and map their surroundings. Here, mutant mice tended to solve the task using a fixed, body-centred rule, for example, consistently turning left or right, rather than building a flexible mental map of the maze.
This pattern echoes what has been described behaviourally in some individuals with ASD.
This reliance on left/right brain learning may help explain why the affected mice were less able to flexibly adapt their memory to new situations than control animals.
The research provides new insight into the neural processes that may contribute to differences in explicit memory, and its flexible use, in autism.
"The findings help us understand how the brain builds memories and adapts to changing situations, abilities we all rely on in everyday life, and that may be experienced differently in autism spectrum disorder," Associate Professor Dehorter said.
This study was published in eLife.
