Physiology and Biophysics Faculty

Research Interests

We are interested in how nerve cells form precise synaptic connections with one another and how those connections normally function. The problem of how neurons form synapses is important not only during embryonic development, but also during neuronal regeneration and recovery from injury. In order to study individual, identified neurons in a functioning nervous system, we have focused on the nervous system of the leech. Its neurons and glia are like those in higher animals, including humans, and they regenerate synaptic connections accurately. In the leech, particular cellular components can be easily manipulated to determine (1) what influences growing axons as they seek synaptic targets, (2) the effectiveness of particular synaptic contacts, and (3) the role of individual neurons in modification of behavior.

Our results, using techniques including electrophysiology, cell marking, laser microsurgery, in situ hybridization and electron microscopy, show that after nerve injury the severed distal stump of the axon, ensheathing glia, and mobile microglial cells play crucial roles in repair. Certain cells in the embryo and following nerve injury express molecules such as laminin that promote axon growth and repair. Other work in the lab has examined the relationship between neuron structure and the pattern of synaptic transmission at dendritic branches, particularly as influenced by conduction block and reflection of action potentials at branch points. In collaboration with Dr. Christie Sahley at Purdue University, we have also identified a single neuron, the S cell, essential for non-associative learning; and regeneration of its synapse restores that learning.

• Google Scholar Citations
• PubMed Citations

Selected Publications

1. Urazaev AK, Arganda S, Muller KJ, and Sahley CL (2007) Lasting changes in a network of interneurons after synapse regeneration and delayed recovery of sensitization. Neuroscience.
2. Kloos AD, Muller KJ, and Modney BK (2007) Atypical embryonic synapses fail to regenerate in adulthood. J Comp Neurol. 505:404-411.
3. Eugenin JL and Muller KJ (2007) Medullary pacemaker neurons are essential for both eupnea and gasping in mammals vs. medullary pacemaker neurons are essential for gasping, but not eupnea, in mammals. J Appl. Physiol 103:724-727.
4. Cruz GE, Sahley CL, and Muller KJ (2007) Neuronal competition for action potential initiation sites in a circuit controlling simple learning. Neuroscience 148:65-81.
5. Ngu EM, Sahley CL, and Muller KJ (2007) Reduced axon sprouting after treatment that diminishes microglia accumulation at lesions in the leech CNS. J Comp Neurol. 503:101-109.
6. Eugenin J, von Bernhardi R, Muller KJ, and Llona I (2006) Development and pH sensitivity of the respiratory rhythm of fetal mice in vitro. Neuroscience 141:223-231.
7. Crisp KM and Muller KJ (2006) A 3-synapse positive feedback loop regulates the excitability of an interneuron critical for sensitization in the leech. J Neurosci. 26:3524-3531.
8. Eugenin J, Nicholls JG, Cohen LB, and Muller KJ (2006) Optical recording from respiratory pattern generator of fetal mouse brainstem reveals a distributed network. Neuroscience 137:1221-1227.
9. Duan Y, Panoff J, Burrell, BD, Sahley CL and Muller KJ (2004) Repair and regeneration of functional synaptic connections: Cellular and molecular interactions in the leech. Cell. Mol. Neurobiol. 25(2):441-50.
10. Burrell BD, Sahley CL, and Muller KJ (2003) Progressive recovery of learning during regeneration of a single synapse in the medicinal leech. J. Comp. Neurol. 457: 67-74.
11. Duan Y, Haugabook SJ, Sahley CL, and Muller KJ (2003) Methylene blue blocks cGMP production and disrupts directed migration of microglia to nerve lesions in the leech CNS. J. Neurobiol. 57:183-192.
12. De-Miguel FF, Muller KJ, Adams WB, Nicholls JG (2002) Axotomy of single fluorescent nerve fibers in developing mammalian spinal cord by photoconversion of diaminobenzidine. J. Neurosci. Methods. 117(1):73-9.
13. Burrell BD, Sahley CL, Muller KJ (2002) Differential effects of serotonin enhance activity of an electrically coupled neural network. J Neurophysiol. 87(6):2889-95.
14. Baccus SA, Sahley CL, Muller KJ (2001) Multiple sites of action potential initiation increase neuronal firing rate. J Neurophysiol. 86(3):1226-36.
15. Kumar SM, Porterfield DM, Muller KJ, Smith PJS, and Sahley CL (2001) Nerve injury induces a rapid efflux of nitric oxide (NO) detected with a novel NO microsensor. J. Neurosci. 21: 215-220.
16. Burrell BD, Sahley CL, Muller KJ (2001) Non-associative learning and serotonin induce similar bi-directional changes in excitability of a neuron critical for learning in the medicinal leech. J Neurosci. 21(4):1401-12.
17. Chen A, Kumar SM, Sahley CL and Muller KJ (2000) Nitric oxide influences injury-induced microglial migration and accumulation in the leech CNS. J. Neurosci. 20: 1036-1043.
18. Baccus SA, Burrell, BD, Sahley, CL, and Muller KJ (2000) Action potential reflection and failure at axon branch points cause stepwise changes in EPSPs in an interneuron essential for learning. J. Neurophysiol. 83: 1693-1700.

Curriculum Vitae

• 1966 S.B. Physics, University of Chicago
• 1971 Ph.D. Biology/Physiology, Massachussetts Institute of Technology
• 1971-1975 Postdoctoral Fellow, Neurobiology and Anatomy, Harvard Medical School
• 1975-1983 Staff Member, Embryology, Carnegie Institution, Baltimore
• 1978-1983 Assistant and Associate Professor, Biophysics, Johns Hopkins University
• 1991-1998 Chair, Neuroscience Program Steering Committee
• 2001 Chair, Workshop/Symposia Funding Programme of the International Brain Research Organization (IBRO)
• 1983-present Professor, Dept. of Physiology and Biophysics, University of Miami School of Medicine

Past Lab Members