Wilhelmina Robertson Professor and Chair - Department of Neuroscience Director of Neuroscience Initiatives Ph.D., The University of Illinois, Champaign-Urbana, 1977 One Baylor Plaza Baylor College of Medicine Houston TX, 77030 Telephone: 713-798-1468 - Fax: 713-798-1476 Email: friedlan@bcm.edu

Synapses are critical communication sites whereby individual neurons transmit and integrate information to their neighboring cells. Understanding the functional properties of these sites, particularly in the cerebral cortex and their capacity for dynamic regulation by experience and recent activity is key to understanding sensory perception and information processing, storage and retrieval of memories and the mechanisms that underlie brain disorders that corrupt the capacity to carry out these functions.

Dr. Friedlander's laboratory investigates the dynamic properties of synapses in the visual cerebral cortex. The main focus of this research is understanding synaptic communication between individual neurons within the cortical layers and the processes that control the efficiency of transmission (synaptic plasticity) throughout the lifespan. In particular, the Friedlander lab utilizes the living in vitro brain slice experimental preparation to identify, target and record the electrical signals from individual pairs of synaptically connected neurons within the cortical microcircuit during periods of baseline activity and after induction of molecular signaling cascades that cause long term potentiation (LTP) or depression (LTD) of synaptic transmission. By combining whole cell patch clamp recording from individual synaptically connected neuronal partners and the use of ratiometric fluorescence calcium imaging, the role of postsynaptic calcium signals in this plasticity induction process is evaluated.

Certain sets of cortical synapses are biased towards up- or down-regulation of their efficiency in response to common conditioning procedures - these differences are being studied with respect to the kinetics and profiles of the intracellular calcium signals that trigger them, including the calcium sources from a variety of transmembrane and intracellular compartments.

Other projects in the laboratory are investigating the computational processes performed by cortical neurons as they receive varying temporal patterns of synaptic inputs in order to understand how an individual cell integrates the calcium signals associated with these patterns, converting them to molecular signaling sequences that trigger appropriate changes in synaptic efficiency. The role of diffusible extracellular signaling molecules in these processes (such as nitric oxide that is produced by cortical neurons in response to synaptic NMDA glutamate receptor activation) is also studied utilizing a combination of single cell electrophysiological activation and optical imaging of nitric oxide in intact living brain slices in order to quantify the spatio-temporal sphere of influence of such signals and their capacity to link neighboring synapses into volummetric integration units.

In addition to understanding the processing of information between synapses within the traditional neocortical layers, the Friedlander lab also explores the capacity for synaptic communication and modulation of the overlying cerebral cortex from neurons that are scattered below the cortical laminae within the white matter. Although these white matter neurons are classically viewed to only play a role only in early brain development before elimination by programmed cell death, many of these neurons survive and are strategically positioned to gate the flow of information within the overlying cortical synaptic networks. The mechanisms of this function are under active investigation.

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Friedlander, MJ and Torres-Reveron, J. The changing roles of neurons in the cortical subplate. Frontiers in Neuroanatomy, 3 (15), 1-8, 2009 (Epub ahead of print).

Saez, I and Friedlander, MJ. Plasticity outcomes at individually identified synaptic connections within layer 4 of neocortex. J. Neurosci. in press, 2009.

Saez I, Friedlander MJ. Synaptic output of individual layer 4 neurons in guinea pig visual cortex. J Neurosci. 2009 Apr 15;29(15):4930-44.

Torres-Reveron J, Friedlander MJ. Properties of persistent postnatal cortical subplate neurons. J Neurosci. 2007 Sep 12;27(37):9962-74.

Ismailov I, Kalikulov D, Inoue T, Friedlander MJ. The kinetic profile of intracellular calcium predicts long-term potentiation and long-term depression. J Neurosci. 2004 Nov 3;24(44):9847-61.

Schrader LA, Perrett SP, Ye L, Friedlander MJ. Substrates for coincidence detection and calcium signaling for induction of synaptic potentiation in the neonatal visual cortex. J Neurophysiol. 2004 Jun;91(6):2747-64.

Perrett SP, Dudek SM, Eagleman D, Montague PR, Friedlander MJ. LTD induction in adult visual cortex: role of stimulus timing and inhibition. J Neurosci. 2001 Apr 1;21(7):2308-19.

Kara P, Friedlander MJ. Arginine analogs modify signal detection by neurons in the visual cortex. J Neurosci. 1999 Jul 1;19(13):5528-48.

Dudek SM, Friedlander MJ. Developmental down-regulation of LTD in cortical layer IV and its independence of modulation by inhibition. Neuron. 1996 Jun;16(6):1097-106.

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Alfred P. Sloan Foundation Neuroscience Fellow

William C. Menninger Award for Distinguished Contribution to Mental Health Research

Founding President - Association of Medical School Neuroscience Department Chairpersons (AMSNDC)

Evelyn F. McKnight Brain Research Foundation Endowed Professorship

President Council of Academic Societies of AAMC

Neuroscience Section Editor Journal of Experimental Biology and Medicine

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• Olivia Fitch (Neuroscience)
• Tara Huddleston (Neuroscience)

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Images of a visual cortex pyramidal neuron attached to a micropipette under patch clamp configuration and filled with the ratiometric calcium indicator, Fura-4F. The pseudocolors indicate the changes in the intracellular calcium concentration in response to paired activation of synaptic inputs with coincident direct postsynaptic depolarization to induce changes in synaptic efficiency (either LTP or LTD). (from Ismailov, Kalikulov and Friedlander, J. Neuroscience, 2004).

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