Spring 2017 Newsletter
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The Burger Lab: Resolving life's symphony of sounds
We all understand the importance of organization in our everyday lives, and how much it helps us to make sense of, and function in our surroundings. Likewise, our brains organize neural circuits to help them sort out important information about the world around us from the myriad of stimuli that we encounter. It’s known that these circuits are organized early in development and are refined with experience throughout childhood. This developmental process is still poorly understood, but fundamental to how our brains process information in a meaningful way.
Let’s take, for example, a single sensory neural circuit like the one that gives you the sense of hearing. Hearing begins in the ear where a coiled structure called ‘the cochlea’ is home to the cells that convert mechanical sound energy into neural activity. As sound enters the ear, hair cells located along the cochlea are displaced causing an electrical signal to be produced at the base of the hair cell and these signals are ultimately sent to the brain over thousands of nerve fibers from each ear. We listen to complex sounds every day, so it is hard to imagine how the brain manages to sort out all of this information to construct our perception of music, laughter, or language.
The key to this puzzle is that every sound frequency (experienced as pitch) is processed by different sets of neurons, each running in parallel from the ear to the brain, similar to the way channels on your radio dial are each tuned to a particular radio frequency. Thus, the main job of the cochlea is to organize frequencies and split a complex job up among different cells, each processing only a small component of the sound stimulus.
The ear further simplifies this complexity with two key strategies that are interesting from a neuroscience perspective. The first is anatomical, such that neurons are spatially ordered in the ear from high to low frequencies. This creates a topographic map of frequencies, a property referred to as ‘tonotopy.’ Tonotopic spatial organization persists throughout all auditory centers in the brain so that the particular location of a neuron will also indicate its preferred frequency. The second strategy is even more remarkable and depends on processing characteristics of each individual neuron. That is, these neurons physiologically (or electrically) “tune” themselves to be most responsive to a narrow range of frequencies and reject input that doesn’t fit with their preferred frequency. The Burger lab demonstrated some of these properties in recent published work (Oline and Burger, 2014; Oline et al., 2016). Next, Lashaka Jones, a graduate student in the lab, is taking advantage of these findings to determine how these properties arise in the brain in the first place.
There are two compelling theories as to how these organizational strategies develop within the ear and brain. The first suggests that the tonotopic properties first arise in the ear, and then these properties drive the frequency specific organizational development of the auditory neurons in the brain. Alternatively, it is possible that the brain’s organization develops independently of the ear, instead relying on cues present in the developing brain itself to establish tonotopic patterns. The optimum way to test which theory is supported would be to disrupt tonotopic organization in the ear, without disrupting hearing. Recent breakthroughs are allowing us to do exactly that. Our collaborators in the lab of Dr. Matt Kelley at the National Institutes of Health recently demonstrated that the tonotopic organization of the inner ear of the embryonic chick can be disrupted by introducing genes into the developing ear that block the normal signaling molecules that establish tonotopy.
In collaboration with the Kelley lab, Lashaka Jones and other members of the Burger lab are following this strategy to create chicks that develop with one normal and one ‘disrupted’ or non-tonotopic ear using a technique called in ovo plasmid electroporation. This technique allows us to drive expression of particular genes in the embryo’s developing ear.
Following development we will then examine the impact of the “disrupted tonotopic pattern” within the ear on the maturation of auditory neurons within the brain. We are particularly interested in the chick cochlear nucleus, nucleus magnocellularis (NM). This brain region is the first to receive input from the ear, and under normal conditions will follow the tonotopic pattern of the ear. We have fully characterized frequency-specific electrical properties that are unique to these neurons. Thus, using the newly genetically manipulated animals, we are able to resolve the degree to which the highly specialized properties of these neurons depend on normal input from the ear.
These will be the first studies to investigate the developmental dependence of brain neurons on their inputs from the ear to establish their fundamental computational properties. These studies will give us a greater understanding of the principles the brain uses to create its precise organization. It is this exquisite organization that ultimately endows each of us with the ability to resolve life’s symphony of sounds.
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