Tiered Mentoring Program
Synaptic changes in the Auditory Midbrain during Middle and Old Age
Jeffrey G. Mellott, Ph.D., Associate Professor of Anatomy and Neurobiology at Northeast Ohio Medical University (NEOMED)
Our lab examines the synapses of the aging auditory midbrain. As you age, inhibition is downregulated across the brain in both a compensatory and maladaptive fashion. In the auditory midbrain, inhibition is initially downregulated to compensate for the loss of excitation due to damaged hair cells in the cochlea. However, the continued loss of inhibition at old age leads to temporal processing deficits that contribute to age-related hearing loss. One of our primary goals is to better understand how synapses are changing during middle age, (when hearing deficits are not common), and old age (when hearing deficits are very common).
To accomplish our goals we use a variety of anatomical and microscopic techniques. Specifically, for the proposals below, we use transmission electron microscopy to examine synapses at the ultrastructural level to detail changes to the balance of inhibitory and excitatory synapses, the synaptic length, bouton size, mitochondria morphology, the number of vesicles, and postsynaptic targeting. We also employ single molecule fluorescent in situ hybridization (smFISH) to detect individual mRNA of a given inhibitory cell type.
Project #1
For decades the age-related downregulation of inhibition in the auditory midbrain has been tied to the loss of GABA, the main inhibitory neurotransmitter of the central nervous system. However, recent studies have identified that a subset of GABAergic cells in the auditory midbrain express Neuropeptide Y (NPY) to dampen neural excitability. Whether NPY is downregulated, and potentially contributing to the overall reduction of inhibition in the aging auditory midbrain is unknown. We are using smFISH to detect mRNA for NPY and glutamic acid decarboxylase (GAD; enzymatic precursor for GABA) to determine if NPY expression changes during middle and old age across GAD cells of varying size.
The primary goal of the student will be to quantify NPY and GAD mRNA in the auditory midbrain. As time goes on, the analysis may expand to other nuclei such as the hippocampus. Students will initially learn how to use a fluorescent microscope, Neurolucida software and develop a basic understanding of neuroanatomy throughout the central nervous system. If time permits, the student will attend weekly meetings, and may also present a paper to the lab once per semester. Once proficient with the analysis, the student may be trained on tissue processing for smFISH.
Project #2
There have been numerous studies in the recent years linking hearing loss in those develop Alzheimer’s Disease (AD). As hearing loss can be mitigated, and to some degree preventable, the increasing view is that improving one’s hearing may delay the onset of AD. Specifically, central gain (increased neural excitability; presumably from lost inhibition) in the auditory system may serve as an early biomarker for the diagnosis of AD. As such, our lab has developed a collaboration in order to examine the ultrastructure of inhibitory synapses in the auditory midbrain of a “normal” aging model and a model of AD. We are using immunogold transmission electron microscopy to assess the ultrastructure of synapses between our two models.
The primary goal of the student will be to learn how to characterize neural ultrastructure in the auditory midbrain. Students will analyze properties of the pre- and postsynaptic elements of synapses, analyze myelination on populations of axons and detail the morphology of blood vessels. If time permits, the student will attend weekly meetings, and may also present a paper to the lab once per semester. Once proficient with the analysis, the student may be trained on tissue processing for immuno electron microscopy.