CRISPR technology has revolutionized genetics research, enabling scientists to edit genes with unprecedented precision. Recently, researchers at Kobe University developed a new method for modifying embryonic stem cells using CRISPR, creating a bank of 63 mouse embryonic stem cell lines containing the mutations most strongly associated with autism spectrum disorder (ASD). This breakthrough achievement has shed light on the hidden causes of ASD.

For decades, scientists have known that genetics play a significant role in the development of ASD. However, pinpointing the precise cause and mechanism remained elusive due to the lack of a standardized biological model for studying the effects of different mutations associated with the disorder. To address this challenge, Takumi Toru and his team at Kobe University embarked on a journey to create a reliable model by combining conventional manipulation techniques for mouse embryonic stem cells with CRISPR gene editing.

The new method proved highly efficient in making genetic variants of these cells, allowing the researchers to produce 63 mouse embryonic stem cell lines containing the mutations most strongly associated with ASD. These cell lines were further developed into various cell types and tissues, even generating adult mice with their genetic variations. The analysis of these cell lines revealed that autism-causing mutations often result in neurons being unable to eliminate misshapen proteins.

This finding is particularly interesting since the local production of proteins is a unique feature in neurons, and a lack of quality control of these proteins may be a causal factor of neuronal defects in ASD. Takumi expects that this achievement will be an invaluable resource for researchers studying autism and searching for drug targets. Moreover, the genetic variants studied are also implicated in other neuropsychiatric disorders such as schizophrenia and bipolar disorder, making this library potentially useful for studying these conditions as well.

This research was funded by various organizations, including the Japan Society for the Promotion of Science and the National Center of Neurology and Psychiatry. The study demonstrates the potential of CRISPR technology to reveal the hidden causes of complex diseases like ASD, paving the way for future discoveries and treatments.

The Brain’s Hidden Patterns: Uncovering the Secret to Flexibility and Stability

For decades, scientists believed that the brain used a single, shared transmission site for all types of plasticity. However, a groundbreaking study from researchers at the University of Pittsburgh has challenged this assumption, revealing that the brain employs distinct transmission sites to achieve different types of plasticity.

The study, published in Science Advances, offers a deeper understanding of how the brain balances stability with flexibility – a process essential for learning, memory, and mental health. By uncovering the hidden patterns of the brain’s transmission sites, researchers hope to shed light on the underlying mechanisms that govern our thoughts, emotions, and behaviors.

Neurons communicate through synaptic transmission, where one neuron releases chemical messengers called neurotransmitters from a presynaptic terminal. These molecules travel across a microscopic gap called a synaptic cleft and bind to receptors on a neighboring postsynaptic neuron, triggering a response.

Traditionally, scientists believed that spontaneous transmissions (signals that occur randomly) and evoked transmissions (signals triggered by sensory input or experience) originated from one type of canonical synaptic site and relied on shared molecular machinery. However, the research team led by Oliver Schlüter discovered that the brain instead uses separate synaptic transmission sites to carry out regulation of these two types of activity.

The study focused on the primary visual cortex, where cortical visual processing begins. The researchers expected spontaneous and evoked transmissions to follow a similar developmental trajectory, but instead found that they diverged after eye opening.

As the brain began receiving visual input, evoked transmissions continued to strengthen. In contrast, spontaneous transmissions plateaued, suggesting that the brain applies different forms of control to the two signaling modes. To understand why, the researchers applied a chemical that activates otherwise silent receptors on the postsynaptic side, causing spontaneous activity to increase while evoked signals remained unchanged.

This division likely enables the brain to maintain consistent background activity through spontaneous signaling while refining behaviorally relevant pathways through evoked activity. This dual system supports both homeostasis and Hebbian plasticity – the experience-dependent process that strengthens neural connections during learning.

“Our findings reveal a key organizational strategy in the brain,” said Yue Yang, a research associate in the Department of Neuroscience and first author of the study. “By separating these two signaling modes, the brain can remain stable while still being flexible enough to adapt and learn.”

The implications could be broad. Abnormalities in synaptic signaling have been linked to conditions like autism, Alzheimer’s disease, and substance use disorders. A better understanding of how these systems operate in the healthy brain may help researchers identify how they become disrupted in disease.

“Learning how the brain normally separates and regulates different types of signals brings us closer to understanding what might be going wrong in neurological and psychiatric conditions,” said Yang.

The science of tickling has been shrouded in mystery for over 2000 years, leaving even the great philosophers Socrates and Charles Darwin baffled. Despite its ubiquity in human interaction, from playful teasing between parents and children to social bonding and emotional expression, the intricacies of tickling remain poorly understood. Neuroscientist Konstantina Kilteni argues that it’s time to take tickle research seriously, shedding light on the complex interplay of motor, social, neurological, developmental, and evolutionary aspects involved.

One of the most intriguing questions surrounding tickling is why we can’t tickle ourselves. Our brain appears to distinguish between self-induced and external stimuli, effectively “switching off” the tickling reflex when we know exactly where and when we’ll be tickled. This phenomenon has sparked interest in understanding what happens in our brain when we’re subjected to ticklish sensations.

Research suggests that people with autism spectrum disorder (ASD) perceive touches as more ticklish than those without ASD, offering a unique window into differences in brain development and function between individuals with and without the condition. Investigating this difference could provide valuable insights into the neurobiology of ASD and potentially inform strategies for better understanding and supporting individuals on the autism spectrum.

From an evolutionary perspective, the purpose and significance of tickling remain unclear. Kilteni notes that even apes like bonobos and gorillas exhibit responses to ticklish touches, while rats have been observed displaying similar behaviors. These observations raise questions about the role of tickling in human evolution and development, as well as its potential functions in social bonding and emotional expression.

To tackle these questions, Kilteni has established a specialized lab dedicated to studying tickling, where researchers can control and replicate various types of ticklish stimuli using mechanical devices like the “tickling chair.” By meticulously recording brain activity and physical reactions such as heart rate, sweating, breathing, laughter, and screaming responses, scientists hope to unlock the secrets of tickling and shed light on its significance in human biology and behavior.

As research continues to unravel the mysteries of tickling, it’s clear that this seemingly simple phenomenon holds a wealth of complexity and intrigue. By taking tickle research seriously, scientists like Kilteni aim to reveal new insights into human brain development, social bonding, emotional expression, and even the intricacies of ASD. The journey ahead promises to be fascinating, as we continue to explore the elusive science of tickling.