HysonLab Overview: Contact information

The majority of work in the lab examines the effects of deafness on the developing brain. This works bridges two broad themes:

            1) The role of sensory experience in brain development, and

            2) The factors that control the life and death of neurons.

Early experience and cell death

The importance of early experience in brain development has come to be so well accepted that it is now a matter of public policy. Parents are instructed to read to your children, play classical music, teach them a foreign language, get them music lessons, etc. The emphasis on boosting early experiences comes, in part, from a variety of studies showing that early sensory experience plays a role in establishing innervation patterns of the brain and even governs the life and death of young neurons. Effects of sensory deprivation have been observed in every sensory system. Our laboratory group investigates this phenomenon in the brain stem auditory system of the chick.

Why do we care about dying cells?

Most of the time, we want to keep our brain cells alive. A wide variety of neurodegenerative diseases, such as Alzheimer's, affect millions of people. Cells do not simply fade away and die, but rather, they typically go through a distinct sequence of events that actively leads toward their demise. If we fully understand these cell death cascades, we may be able to tap into them so as to prolong the life of neurons (as in the case of neurodegenerative disease) or to "encourage" cells to die (as in the treatment of cancer).

 
 
HysonLab 2005
The people behind the research (From top left): Alexander Nicholas, Rick Hyson, Todd Stincic, Stan King, Angela Bush and Katte Carzoli.
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Model system: Deafness leads to cell death

The brain stem auditory system of the chick is an excellent model system for examining cell death cascades. In this system, we do not have to introduce pathogens or cause physical trauma to the brain to induce cell death.

The relatively simple and symmetric organization of this system makes it ideal for investigating how activity influences neurons. The cochlear nucleus, nucleus magnocellularis (NM), receives its only excitatory input from the auditory nerve (n VIII) on the same side of the brain. Removing one cochlea eliminates all excitatory drive to NM on one side of the brain while NM neurons on the opposite side of the brain retain their normal levels of activity. This allows for powerful within-subject comparisons of normal and deprived neurons on opposite sides of the same brain.

Cell death can be induced in young auditory neurons by eliminating sensory experience. Early deafness produces a series of rapid and dramatic changes in NM. If the chick is deaf in one ear, approximately 20 - 30% of NM cells on the deaf side of the brain will die within a couple of days.


The above pictures show NM cells on opposite sides of the same brain as they appear 24 hrs after one cochlea is removed . Using a nissl stain, we see that approximately 20-30% of the cells are dying (red arrows).
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Cell death cascades

One intriguing aspect of  deafness-induced cell death in this system is that only a subpopulation of deprived neurons die. We can see signs of which cells are going to die and which are going to live just a few hours after deafness. This rapid time course will allow us to determine the sequence of events leading toward death (or survival). These events can be examined by using methods that allow us to see which cells are turning on particular genes or contain particular proteins.


Messenger RNA for a presumed cell-survival gene called bcl-2 is upregulated in a subpopulation of NM neurons a few hours after cochlea removal.  In the above photomicrograph, the black silver grains show the location of bcl-2 mRNA.  Many of the blue stained NM cell bodies are unlabeled.   

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What is necessary for life?

The fact that cells die if they are deprived of their sensory input is an interesting phenomenon, but what we really want to know is WHY they die. Apparently, these cells need something that is released from the active auditory nerve. If deprived of this substance, they will die. Our studies, using a brain slice preparation of this system, suggest that the neurotransmitter, glutamate , is the chemical released from the auditory nerve that is important for keeping these neurons healthy. We are currently determining the specific receptors responsible for glutamate's survival-promoting role.  See Hyson 1998 for an example of this line of research.


Picture of a brain slice in the recording chamber. It is being held in place by nylon mesh. The auditory nerve (drawn in yellow) projects to NM neurons (red), which project no nucleus laminaris neurons (blue) on both sides of the brain.

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Neurophysiology and Neuropharmacology

How the brain processes sensory information is a fundamental question in neuroscience and the relatively simple organization of the chick brain stem auditory system makes it an appropriate model system for these investigations.

The cells in the cochlear nucleus, nucleus magnocellularis, are round cells with little or no dendrites. They receive a powerful excitatory input from the auditory nerve, but also receive an inhibitory (GABAergic) input. With the aid of a video camera and    infrared differential interference contrast (IR-DIC) optics, we can view individual neurons in the living slice .  This allows us to guide our electrode right to the cell of choice to perform our electrophysiological measurements.  In this picture, the patch electrode, entering from the right, is contacting a round cell in NM.

The neuropharmacology of these cells can be investigated either by applying small amounts of chemical near the cell, or by adding known concentrations of the pharmacological agent to the medium bathing the slice.

Cells can also be filled with dye for anatomical investigations.

After recording from this interneuron in a brain slice preparation, the cell was filled with a dye called neurobiotin. The section on the left shows the labeled cell body and the next section (right) contains much of the cell's dendritic tree. 

Coding sound location:

One cue that we use for determining the location of a sound source is the difference in the timing of acoustic information at the two ears. Simply put, if a sound source is located off to one side, sound reaches the near ear slightly before it reaches the ear on the opposite side of the head. A neural circuit in the brain stem analyzes this interaural (between ear) time difference and translates it into a neural "place code". That is, different neurons are maximally activated depending on where the sound is located. We have been investigating this circuit using the brain slice preparation.

An example of this work can be seen in the article by Brückner and Hyson .

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Our ratiometric ion imaging system allows another technique for examining physiological characteristics of these neurons. This system allows for real time imaging of ionic concentrations within the cell.
Click start arrow to see movie.
For example, changes in intracellular calcium concentrations can be visualized using a calcium indicator dye called fura 2. The above movie shows the change in the fluorescence when calcium enters the cell. In this false color image, cells turn more green when calcium concentration increases.  This change was induced by applying a chemical to media bathing the brain slice.
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