Research Program Summary

My research program is directed at understanding the processes that regulate alterations in synaptic efficiency between neurons within the cerebral cortex—synaptic plasticity—and how these cellular processes are affected during brain development, after experience including learning and in response to brain injury. Specifically, my laboratory utilizes quantitative single neuron patch clamp electrophysiological methods along with cellular and subcellular imaging to visualize the changes in structure and calcium signals that underlie alterations in functional synaptic connectivity within the mammalian neocortex. This work is carried out in vitro in acute living brain slice preparations with simultaneous whole cell patch clamp recording from multiple cortical neurons that are synaptically interconnected. This approach allows for the application of quantal analysis to determine how the induction of synaptic plasticity affects a variety of components of synaptic transmission including probability of presynaptic neurotransmitter release in response to a single action potential in an individual cortical neuron and the quantal size or postsynaptic neurotransmitter receptor availability. We have found that surprisingly, apparently like-type sets of interconnected cortical neurons exhibit wide variability in their baseline synaptic transmission properties and in their plasticity behavior in response to an identical synaptic conditioning protocol. We are currently studying the origin of the variability of synaptic plasticity between different sets of cortical synapses of otherwise like-type, specifically evaluating to what degree intrinsic differences in gene expression vs. environmental activity during early brain development and throughout life modify the capacity, likelihood and polarity of changes in synaptic efficiency. In addition, we have discovered that the temporal patterns of incoming synaptic activity impinging onto a single neocortical neuron can differentially modulate plasticity responses, even when the overall frequency of the activation is identical. We are using this approach to explore plasticity induction processes in the normal brain and after brain injury. This line of investigation is also aimed at identifying specific patterns of synaptic activation that are most effective at accessing the downstream plasticity signaling pathways in the injured brain as an approach to neurorehabilitation.

Education and Training

• University of Virginia: Postdoctoral fellowship
• University of Illinois: Ph.D.

Previous Positions

• Baylor College of Medicine
  Wilhelmina Robertson endowed Professor of Neuroscience
  Chair, Neuroscience
  Director, Neuroscience Initiatives

Awards and Honors

• AAMC Board of Directors Distinguished Service Member, 2012
• Wilhelmina Robertson Endowed Chair in Neuroscience, Baylor College of Medicine, 2005
• Evelyn F. McKnight Professor of Learning and Memory in Aging, University of Alabama at Birmingham, 2004–2005

Selected Publications

• Zhu PJ, Huang W, Kalikulov D, Yoo JW, Placzek AN, Stoica L, Zhou H, Bell JC, Friedlander MJ, Krnjević K, Noebels JL, Costa-Mattioli M. (2011). Suppression of PKR Promotes Network Excitability and Enhanced Cognition by Interferon-γ-Mediated Disinhibition. Cell, 147(6):1384-96.
• Friedlander, Michael J.; Andrews, Linda; Armstrong, Elizabeth G.; Aschenbrenner, Carol; Kass, Joseph S.; Ogden, Paul; Schwartzstein, Richard; Viggiano, Thomas R.. (2011). What Can Medical Education Learn From the Neurobiology of Learning?. Academic Medicine, 86(4):415-420.
• Saez, I and Friedlander, MJ. (2009). Synaptic output of individual layer 4 neurons in guinea pig visual cortex. J. Neurosci, 29:4930-4944.
• Saez, I and Friedlander, MJ. (2009). Plasticity between neuronal pairs in layer 4 of visual cortex varies with synapse state. J. Neurosci, 29:15286-15298.
• Reveron-Torres, J. and Friedlander, M.J.. (2007). Properties of persistent postnatal cortical subplate neurons. J. Neurosci, 27:9962-9974.
• Perrett, S., S. Dudek, D. Eagleman, P. Montague and M.J. Friedlander. (2001). LTD induction in adult visual cortex: Role of stimulus timing and inhibition. J. Neurosci, 21:2308-2319.
• Kara, P. and M.J. Friedlander. (1999). Arginine analogues modify signal detection by neurons in the visual cortex. J Neurosci, 19:5528-5548.
• Dudek, S.M. and M.J. Friedlander. (1996). Developmental down-regulation of LTD in cortical layer IV and its independence of modulation by inhibition. Neuron, 16:1097-1106.
• Montague, P.R., C. Gancayco, M.J. Winn, R.B. Marchase and M.J. Friedlander. (1994). Role of NO production in NMDA receptor-mediated neurotransmitter release in cerebral cortex. Science, 263:973-977.

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