Making Sense of the Noise: Uncovering the Function of an Autism-Associated Gene
Imagine a bustling farmer’s market. As you stroll through the various vendors, you can’t help but smell the freshly baked goods while sampling one of the fresh fruits nearby, all while surrounded by a symphony of sounds – vendors chatting with customers, laughter from a group next to you, and a musician playing an instrument in the distance.
As humans, we rely on our five senses – sight, smell, taste, touch, and sound – to navigate and understand our complex environments. For most individuals, the imagery of a busy farmer’s market may seem like a pleasant and enjoyable experience. However, some individuals, particularly those who have difficulty processing sensory information as in autism spectrum disorder (ASD), might perceive this environment as overwhelmingly loud and unbearable.
ASD affects the process of brain development. Often diagnosed in childhood, autism occurs on a spectrum, as the abbreviation suggests, and no two individuals present with the same condition. Although all of the senses may be affected, hearing and sound processing are greatly altered in many individuals with ASD. Certain processes in the brain are dedicated to decoding and understanding overlapping sounds in our environment. When these brain processes do not function as intended, such as in individuals with ASD, being in an environment where music is present and multiple conversations can be heard becomes overwhelming and jarring.
While the scientific community has yet to pinpoint a single or main cause of ASD in humans, some research points to specific genes that are altered in those diagnosed with ASD. Contactin associated protein-like 2 – also abbreviated as Cntnap2 – is a specific gene that, when disrupted, can cause problems with language processing and development in humans. This gene is highly present in brain regions associated with sound processing, although the exact function of Cntnap2 within these regions is not fully understood. A recent paper published in 2018 by researchers at Western University in the Journal of Neuroscience presents a potential function of Cntnap2 in sound processing in the brain across development.
Specifically, the research team supported by Dr. Brian Allman and Dr. Susanne Schmid used a specific rodent model that lacks the Cntnap2 gene to better understand the gene’s role in developing normal responses to sound. “Sensory processing differences are a key component of ASD,” says lead author and Ph.D. Candidate Kaela Scott, “and differences have come to light in the way some individuals with ASD respond to sounds.” In particular, the research conducted by Scott first aimed to uncover if Cntnap2 is capable of affecting brain activity associated with sound processing.
Brain activity in the form of electrical waves can tell researchers how responsive a group of neurons, or brain cells, are to a specific stimulus or behaviour. The stimulus in this case is sound. Just as a light switch with a dimmer can alter the brightness of a lightbulb, the activity of neurons can be adjusted in a similar manner. Smaller brain waves can represent a lower level of response by the neuron, while larger brain waves can represent neurons with an increased response to a stimulus. In this study, waves that were measured from brain areas responsible for sound processing were smaller and more delayed in brains without the Cntnap2 gene expression, compared to healthy brains with Cntnap2. “Just like in people [with ASD], the Cntnap2 knockout rodents had a delayed maturation of the brain pathway that deals with sound,” explains Scott.
Understanding the way certain brain regions respond to sound is important in uncovering the function of Cntnap2, but these changes must be linked to behaviour if they are to help us understand ASD. To link brain changes with behaviour, Scott used an acoustic startle response paradigm to explore how subjects with and without Cntnap2 respond to loud, sudden sounds.
Think back to our farmer’s market. As you process the various noises around you – the group of friends chatting, the musician playing an instrument in the background – you suddenly hear a loud noise; the vendor behind you dropped a case of apples, making a startling sound that causes your body to jump and your eyes to twitch. The startle response paradigm is similar to this experience – subjects are in an environment where loud noise is presented, and the physical startle response is measured. Interestingly, Scott discovered that a lack of Cntnap2 results in a larger startle response compared to those with normal Cntnap2 expression.
The altered sound processing in the brain and increased startle response in subjects lacking Cntnap2 is similar to the types of behaviours associated with ASD. Scott sees the potential for this model to be used by others in the scientific field to further study autism-related behaviours. “In the future, we can use this model to uncover the neural mechanism for sound processing, and ultimately as a preclinical model to test for potential treatments.”
Original article:
Scott, K. E., Schormans, A. L., Pacoli, K. Y., De Oliveira, C., Allman, B. L., & Schmid, S. (2018). Altered Auditory Processing, Filtering, and Reactivity in the Cntnap2 Knock-Out Rat Model for Neurodevelopmental Disorders. Journal of Neuroscience, 38(40), 8588-8604.