email: dd.simmons@ucla.edu
phone: 310-794-1228
office: 4214 Life Science Building
research interests: Synaptic plasticity and calcium regulation during development and aging of the peripheral and central auditory system
Education
B.S., Biology, Pepperdine University 1980
Ph.D., Cell & Developmental Biology, Harvard University 1986
Research Interests
Our investigations attempt to understand the cellular and molecular mechanisms of synapse formation and aging associated with cholinergic synapses on hair cells. The efferent cholinergic system is analogous to a sensory feedback system that may increase the gain of the discrimination of acoustic signals. Before the onset of hearing, both efferent and afferent axons make specific synapses with sensory cell targets. In the inner ear, we believe that hair cells may control the initial program of synapse formation, but both afferent and efferent axons are needed to confirm that appropriate connections have been made. As the ear ages, efferent synapses and hair cells are eventually lost. We believe the loss of cholinergic synapses contributes to the deterioration of sensory discrimination. Our studies of synapse formation and degeneration help us understand further the basic issues associated with correctly wiring the brain and inner ear. We use both rodents and amphibian animal models. Rodents such as hamsters, mice and rats are altricial rodents that experience a significant and rapid postnatal maturation of their peripheral and central nervous systems. Both rats and mice are common altricial laboratory animals whose auditory development and aging have been well characterized. In general, the rodent auditory system first responds to airborne sound at approximately P12; and approaches functional maturity between P16 and P30, depending on the parameter being examined. Aging effects start in some mouse strains as early as two months. The bullfrog amphibian papilla (AP) is an ideal model system in which to study synaptogenesis in regenerating hair cells. The bullfrog AP is a low-frequency mechanosensitive endorgan that shares structural and functional similarities with the mammalian cochlea. However, unlike the cochlea, the bullfrog AP has a peripheral growth margin, permitting in vitro studies of synaptic development. It also can be cultured with an intact statoacoustic ganglion and displays both hair cell repair and regeneration after trauma-induced damage, making it useful for comparing these recovery processes. We employ various methods in our attempt to understand the mechanisms of synaptogenesis and aging by efferent and afferent neurons in the inner ear and brainstem. Our general experimental design is: 1) anatomical and immunofluorescent techniques are used to label neurons and extracellular matrix molecules, 2) molecular approaches are used to identify the expression and function of genes involved in hair-cell target selection and synaptogenesis, 3) heterologous cell culture and tissue slice techniques are used to manipulate gene expression in afferent and efferent neurons as well as hair cells, 4) calcium imaging techniques are used to measure functional expression of gene constructs, and 5) otoacoustic emissions are measured to test for inner ear function. In our studies of the bullfrog AP, we use an in vitro culture system that supports both hair cell and neuronal regeneration to study how hair cells acquire, organize, and maintain their synaptic machinery. These studies reveal the time course and temporal order of molecular events that initiate and regulate synaptogenesis in developing and aging hair cells.
Selected Publications
Jenkins, S.A. and D.D. Simmons. 2006. GABAergic neurons in the lateral superior olive of the hamster are distinguished by differential expression of GAD isoforms during development Brain Research 1111 12-25 .
Simmons, D.D., S.W.F. Meenderink, and P. Vassilakis. 2006. Anatomy, Physiology and Function of Aditory End Organs in the Frog Inner Earin Hearing and Sound Communication in Amphibians. Springer Handbook of Auditory Research (ed. P.M. Narins and A.S. Feng) - (Springer-Verlag, ) .
Simmons, D.D.. 2006. Development of the Earin Anatomy and Physiology of Hearing for Audiologists (ed. W. Clark and K.K. Ohlemiller) - (Singular Publishing, ) .
Simmons, D.D.. 2006. Cochlear Efferent Anatomy and Functionin Anatomy and Physiology of Hearing for Audiologists (ed. W. Clark and K.K. Ohlemiller) - (Singular Publishing, ) .
Simmons, D.D.. 2006. Otoacoustic Emissionsin Anatomy and Physiology of Hearing for Audiologists (ed. W. Clark and K.K. Ohlemiller) - (Singular Publishing, ) .
Simmons, D.D.. 2006. Neuroanatomy of Central Auditory Pathways Anatomy and Physiology of Hearing for Audiologists (ed. W. Clark and K.K. Ohlemiller) - (Singular Publishing, ) .
Bergeron, A.L., A. Schrader, D. Yang, A. Osman, and D.D. Simmons. 2005. Expression of the high-affinity choline transporter (ChT1) during development of the rodent cochlea Journal of Association for Research in Otolaryngology 1-15 .
Yang, D.,I. Thalmann, R. Thalmann, and D.D. Simmons. 2004. Expression of alpha and beta parvalbumin is differentially regulated in the rat organ of Corti during development Journal of Neurobiology 58 479-492 .
Simmons D.D. 2003. New frontiers in the amelioration of hearing loss: Part II – Hair cell development, regeneration, protection, and rescue Seminars in Hearing 24 93-96 .
Raji-Kubba, J., P.E. Micevych and D.D. Simmons. 2002. The superior olivary complex of the hamster has multiple periods of cholinergic neuron development Journal Chemical Neuroanatomy 24 75-93 .