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Photo of Steven Stasheff

Steven Stasheff

Assistant Professor,  Pediatrics

Contact Information

Phone: +1 319 335 8250
Email: steven-stasheff@uiowa.edu
Web:

Education

BA, Biology and Physics, University of North Carolina, Chapel Hill
PhD, Pharmacology, Duke University
MD, Duke University School of Medicine
Internship, Pediatrics, Children's Hospital of Philadelphia
Residency, Children's Hospital of Philadelphia
Residency, Pediatric Neurology, Children's Hospital, Boston
Post-Doc, Retinal Neurophysiology, Massachusetts General Hospital
Fellowship, Neuro-ophthalmology, New England Medical Center

Appointments

Primary: Pediatrics
Secondary: Electrical & Computer Engineering
Secondary: Biomedical Engineering

Centers and Program Affiliations

Interdisciplinary Graduate Program in Neuroscience

Research Interests

central nervous system (CNS) plasticity, hereditary retinal degeneration, neurodegenerative disorders, photoreceptor loss

MeSH Terms from Publications

Hippocampus, Kindling, Neurologic, Epilepsy, Retinal Ganglion Cells, Action Potentials, Animals, Evoked Potentials, Axons, Electric Stimulation, Seizures, Receptors, N-Methyl-D-Aspartate, Rats, Retinal Degeneration, Synapses, Baclofen, 2-Amino-5-phosphonovalerate, Culture Techniques, Mice, Mutant Strains, Electrophysiology, Perceptual Disorders, Dendrites, Visual Pathways, Neuronal Plasticity, Anticonvulsants, Synaptic Transmission

Research Summary

The fundamental physiologic mechanisms of neurologic diseases affecting the visual system, and the role that central nervous system (CNS) plasticity may play in both the pathogenesis and potential treatments for such disorders. Ongoing investigations aim to better understand electrophysiologic changes that occur in hereditary retinal degeneration, the most common inherited cause of blindness, and also a central feature of many neurodegenerative disorders in children and adults, including those that cause severe mental retardation, motor disability, and seizures.

Currently proposed therapies for these disorders hinge upon the assumption that even after photoreceptor degeneration, remaining retinal neurons would be able to normally process signals from rescued or replaced photoreceptors, or from direct electrical stimulation. In fact, significant anatomic reorganization of the inner retina occurs, and recent work in my laboratory has identified corresponding physiologic changes that may involve mechanisms of developmental plasticity. The lab uses state-of-the-art multielectrode recording to monitor spontaneous and light-evoked activity simultaneously from 30-90 retinal ganglion cells in normal (wild type, wt) mice or those of the well-studied rd1 mouse model of retinal degeneration. Surprisingly, as the animal becomes blind, retinal ganglion cells do not simply drift into silence as might be expected. Rather, they develop striking hyperactivity (~10 times normal firing rate) that is sustained for many weeks. In fact, ganglion cells pass through at least three stages of activity: 1) normal spontaneous "waves" of correlated firing in early development; 2) increasing spontaneous activity with temporary preservation of light-evoked responses, selective for the OFF pathway; then 3) sustained hyperactivity that lasts for months, well beyond the loss of virtually all photoreceptors and light-evoked responses.

These striking alterations in inner retinal physiology tell us that in the rd1 mouse:
  1. blindness occurs in the face of sustained ganglion cell hyperactivity
  2. these cells remain viable, thus amenable to various treatments, for an extended time despite this activity;
  3. ON and OFF responses are differentially affected in early stages of degeneration.

Since photoreceptor loss begins early and progresses rapidly in rd1 mice, it overlaps substantially with a normal developmental period of highly active synaptic plasticity. Thus, the lab now is comparing several transgenic mouse lines to explore the possibility that developmental plasticity may play an adaptive role in resculpting specific inner retinal circuits such as the ON and OFF pathways. Other avenues of investigation include dissecting changes in the neural code that rd1 ganglion cells use to communicate with the brain, exploring circuit-level and cellular mechanisms that underlie the alterations in their physiologic activity, and determining how widespread these changes are among other neurodegenerative diseases such as neuronal ceroid lipofuscinosis (NCL) and tuberous sclerosis (TS).

Model System

In vitro mouse and rabbit retina
Multielectrode and patch clamp recording



Recent Publications


Show publications
  1. Stasheff, S, Shankar, M, Andrews, M. Developmental time course distinguishes changes in spontaneous and light-evoked retinal ganglion cell activity in rd1 and rd10 mice. J Neurophysiol 105(6):3002-9, 2011. [PubMed]
  2. Thompson, S, Stasheff, S, Hernandez, J, Nylen, E, East, J, Kardon, R, Pinto, L, Mullins, R, Stone, E. Different inner retinal pathways mediate rod-cone input in irradiance detection for the pupillary light reflex and regulation of behavioral state in mice. Invest Ophthalmol Vis Sci 52(1):618-23, 2011. [PubMed]
  3. Stasheff, S. Emergence of sustained spontaneous hyperactivity and temporary preservation of OFF responses in ganglion cells of the retinal degeneration (rd1) mouse. J Neurophysiol 99(3):1408-21, 2008. [PubMed]
  4. Murtha, T, Stasheff, S. Visual dysfunction in retinal and optic nerve disease. Neurol Clin 21(2):445-81, 2003. [PubMed]
  5. Stasheff, S, Masland, R. Functional inhibition in direction-selective retinal ganglion cells: spatiotemporal extent and intralaminar interactions. J Neurophysiol 88(2):1026-39, 2002. [PubMed]
  6. Jeon, C, Kong, J, Strettoi, E, Rockhill, R, Stasheff, S, Masland, R. Pattern of synaptic excitation and inhibition upon direction-selective retinal ganglion cells. J Comp Neurol 449(2):195-205, 2002. [PubMed]
  7. Stasheff, S F, Barton, J J. Deficits in cortical visual function. Ophthalmol Clin North Am 14(1):217-42, x, 2001. [PubMed]
  8. Burack, M A, Stasheff, S F, Wilson, W A. Selective suppression of in vitro electrographic seizures by low-dose tetrodotoxin: a novel anticonvulsant effect. Epilepsy Res 22(2):115-26, 1995. [PubMed]
  9. Stasheff, S F, Hines, M, Wilson, W A. Axon terminal hyperexcitability associated with epileptogenesis in vitro. I. Origin of ectopic spikes. J Neurophysiol 70(3):961-75, 1993. [PubMed]
  10. Stasheff, S F, Mott, D D, Wilson, W A. Axon terminal hyperexcitability associated with epileptogenesis in vitro. II. Pharmacological regulation by NMDA and GABAA receptors. J Neurophysiol 70(3):976-84, 1993. [PubMed]