Neuroscience

Consciousness—the internal awareness that you exist—continues to captivate philosophers and neuroscientists alike. Insight into human consciousness can be gathered from the artificial intelligence (AI) language model ChatGPT. This trained computer chatbot can generate text, answer questions, provide translations, and learn based on the user’s feedback. Large language models like ChatGPT may have many applications in science and business, but how much do these tools understand what we say to them, and how do they decide what to say back? Professor Terrence Sejnowski explored the relationship between the human interviewer and language models to uncover why chatbots respond in particular ways, why those responses vary, and how to improve them in the future.

The spinal cord acts as a messenger, carrying signals between the brain and body to regulate everything from breathing to movement. While the spinal cord is known to play an essential role in relaying pain signals, technology has limited scientists’ understanding of how this process occurs on a cellular level. Now, Associate Professor Axel Nimmerjahn; co-first authors Pavel Shekhtmeyster, Erin Carey, and Daniela Duarte; and colleagues have created wearable microscopes to enable unprecedented insight into the signaling patterns that occur within the spinal cords of mice. The lab’s technological advancement will help researchers better understand the neural basis of sensations and movement in healthy and disease contexts, such as chronic pain, itch, amyotrophic lateral sclerosis (ALS), or multiple sclerosis (MS).

In addition to broader inquiry into consciousness, scientists also ask questions about neuron communication. Itch is a protective signal that animals use to prevent parasites from introducing potentially hazardous pathogens into the body. Itchiness due to something like a crawling insect is known as “mechanical” and is distinct from “chemical” itchiness generated by an irritant, such as a mosquito’s saliva if the mosquito were to bite a person’s arm. While both scenarios cause the same response (scratching), recent research by Professor Martyn Goulding, Associate Professor Sung Han, and colleagues has revealed that, in mice, a dedicated brain pathway drives the mechanical sensation and is distinct from the neural pathway that encodes the chemical sensation. Their findings open up new avenues for therapeutic interventions for patients who experience a range of chronic itch conditions, including atopic dermatitis and psoriasis.

The brain is divided into areas, each containing many millions of neurons connected across thousands of synapses. These synapses, which enable communication between neurons, depend on even smaller structures: message-sending boutons (swollen bulbs at the branch-like tips of neurons), message-receiving dendrites (complementary branch-like structures for receiving bouton messages), and power-generating mitochondria. Professor John Reynolds, co-first authors Courtney Glavis-Bloom and Casey Vanderlip, and colleagues found that brains lose synapses as they age and the synapses that remain show a breakdown in coordination between the size of boutons and the mitochondria they contain. Their findings open an entirely new way of thinking about cognitive decline that could lead to new targets for future therapeutics.

Situated at the intersection of the human immune system and the brain are microglia, specialized brain immune cells that play a crucial role in development and disease. Although the importance of microglia is undisputed, modeling and studying them has remained a difficult task. To overcome this barrier, Professor Rusty Gage, Associate Professor Axel Nimmerjahn, co-first authors Simon Schafer and Abed Mansour, and colleagues developed an organoid model—a three-dimensional collection of cells that mimics features of human tissues. This model allows researchers to study human microglial development and function for the first time in living human-derived tissue. The scientists also examined patient-derived microglia from children with a type of autism spectrum disorder to determine whether brain environment influences the development of more reactive microglia.