For years, schizophrenia has perplexed both the scientific community and the general public alike. Its symptoms are diverse, its causes are elusive, and effective treatments are still far from universal. However, a groundbreaking study published in Science Advances by researchers from RIKEN, led by Akiko Hayashi-Takagi, is shedding new light on this complicated mental health disorder.

Traditionally, research has focused on the density of synapses in the brain to understand schizophrenia. This new study, however, turns the spotlight on the strength of the synapses instead. “We’ve discovered that the appearance of a small number of extra-strong, extra-large synapses may be at the heart of the disorder,” Hayashi-Takagi explains.

Termed “aristocratic” synapses, these extra-large connections were identified in mouse models mimicking genetic factors associated with schizophrenia. When these oversized synapses were active, they effectively bypassed the normal integration process within the brain. Instead of a balanced, “democratic” interplay of synaptic inputs, these aristocratic synapses took control over neuronal firing patterns.

Why is this significant? Neuronal firing is directly linked to the working memory, a pivotal cognitive function that is often impaired in individuals with schizophrenia. In the mouse models, these extra-large synapses led to an increase in neuronal firing, distorting the working memory in the process. The researchers went a step further by comparing the findings with post-mortem brains of individuals diagnosed with schizophrenia and found an overrepresentation of these extra-large synapses.

“The synaptic strength has been largely overlooked in the past, but our findings suggest that this small but mighty group of synapses could be a game-changer in understanding and treating schizophrenia,” said Hayashi-Takagi.

In addition to identifying the presence of these unusual synapses, the research also delved into their inner workings. The extra-large synapses exhibit a heightened calcium response when activated, resulting in an amplification of their excitatory potential. These findings indicate that the extra-large synapses are not just an anatomical anomaly but a functional disruptor as well.

Using optical methods, the study even managed to prevent the generation of these extra-large synapses in the mouse models, effectively restoring the working memory to normal levels. This could open up new avenues for targeted treatments, making the possibility of reversing cognitive impairments in schizophrenia less of a distant dream and more of an immediate scientific objective.

Critics might argue that these findings are preliminary and limited to animal models. However, the researchers assert that their results are corroborated by human post-mortem data, strengthening the case for these extra-large synapses being a key factor in the onset and progression of schizophrenia.

So, what’s next on the horizon? Hayashi-Takagi and her team are keen to expand their research, aiming to refine these optical methods for potential human application and to investigate other psychiatric disorders where these aristocratic synapses may play a role.