OHSU

Agnieszka Z. Bałkowiec, M.D., Ph.D.

Agnieszka BalkowiecAssociate Professor


Joint Appointment: Physiology & Pharmacology, School of Medicine

Research Interests: Development and Plasticity of Neuronal Circuits

For normal function of the nervous system, it is essential that neurons become appropriately connected with each other. During development, neural circuitry is refined in part through changes in number and strength of connections between individual neurons.

A fundamental objective of neurobiology, and the long-range objective of our research, is to understand the role that neuronal activity plays in structural and functional changes in neuronal circuits.

One line of our current research focuses on the regulation of expression, trafficking and release of growth factors by neuronal activity. We have developed a novel ELISA protocol, termed ELISA in situ, which provides a substantially increased level of sensitivity for detecting growth factors synthesized and released by neurons. This innovative tool, combined with electrical field stimulation, calcium imaging, immunocytochemistry, and pharmacological techniques, allows us to examine cellular mechanisms of endogenous growth factor regulation by physiological patterns of neuronal activity.

Another line of our research addresses the role of growth factors in functional maturation and plasticity of neuronal circuits. We study the effects of growth factors on expression and activity of transmitter receptors and ion channels, as well as morphology, of identified neurons. For these studies, we use a combination of in vivo anterograde tracing, patch-clamp recording, immunohistochemical, and digital imaging techniques.

We use three experimental models: 1) visceral sensory pathways that control cardio-respiratory homeostasis, 2) trigeminal sensory pathways, and 3) hippocampal neurons.

Cardiorespiratory homeostasis in general, and blood pressure in particular, are controlled by baroreceptor reflexes. We study developing primary and second order neurons in the arterial baroreflex pathway to reveal mechanisms that govern normal development of the nervous system. In addition, these studies will provide insights into pathophysiology of developmental and other disorders of the cardiorespiratory system, such as Sudden Infant Death Syndrome (SIDS).

Trigeminal sensory pathways play a key role in transmission of sensory information from craniofacial tissues, such as meninges, the temporomandibular joint (TMJ), and teeth. These studies are intended to elucidate cellular and molecular mechanisms relevant to understanding and treatment of several commonly occurring craniofacial pain conditions, such as migraine headaches, disorders of the TMJ, trigeminal neuralgias, and tooth pain.

Neuronal growth factors are required for establishment of hippocampal long-term potentiation (LTP), a phenomenon which underlies memory formation. The goal of our studies utilizing hippocampal neurons is to define the physiological mechanisms of activity-dependent regulation of neuronal growth factors in developing hippocampal neurons. Characterization of the linkage between different patterns of neuronal activity and cellular mechanisms of growth factor regulation will give us a greater insight into the role of these factors in various forms of functional and structural synaptic plasticity, and, therefore, elucidate mechanisms that underlie such brain functions as learning and memory.

Research Support:

National Institutes of Health; American Heart Association

Representative Publications

A.Vermehren-Schmaedick, V.K.Jenkins, H-Y.Hsieh, M.P.Page, V.L.Brooks & A.Balkowiec (2013). Upregulation of brain-derived neurotrophic factor expression in nodose ganglia and the lower brainstem of hypertensive rats. Journal of Neuroscience Research 91: 220-229.

J.L.Martin, A.L.Brown & A.Balkowiec (2012). Glia determine the course of brain-derived neurotrophic factor-mediated dendritogenesis and provide a soluble inhibitory cue to dendritic growth in the brainstem. Neuroscience 207: 333-346.

A.Vermehren-Schmaedick, V.K.Jenkins, S.J.Knopp, A.Balkowiec & J.M.Bissonnette (2012). Intermittent hypoxia-induced expression of brain-derived neurotrophic factor is disrupted in the brainstem of MeCP2-deficient mice. Neuroscience 206: 1-6.

E.Balkowiec-Iskra, A.Vermehren-Schmaedick & A.Balkowiec (2011). Tumor necrosis factor-? increases BDNF expression in trigeminal ganglion neurons in an activity-dependent manner. Neuroscience 180: 322-333.

L.Tarsa, E.Balkowiec-Iskra, F.J.Kratochvil III, V.K.Jenkins, A.McLean, A.Brown, J.A.Smith, J.C.Baumgartner & A.Balkowiec (2010). Tooth pulp inflammation increases BDNF expression in rodent trigeminal ganglion neurons.  Neuroscience 167: 1205-1215.

H-Y.Hsieh, C.L.Robertson, A.Vermehren-Schmaedick & A.Balkowiec (2010). Nitric oxide regulates BDNF release from nodose ganglion neurons in a pattern-dependent and cGMP-independent manner. Journal of Neuroscience Research 88:1285-1297.

A.Balkowiec & E.Balkowiec-Iskra (2010). "Novel Approaches to Studying Activity-Dependent Regulation of Neurotrophins and Neuropeptides in Sensory Pathways from Orofacial Tissues." In: A.Daskalaki (ed.) Informatics in Oral Medicine:Advanced Techniques inClinical and Diagnostic Technologies. IGI-Global.

J.L.Martin, V.K.Jenkins, H-Y.Hsieh & A.Balkowiec (2009). Brain-derived neurotrophic factor in arterial baroreceptor pathways: Implications for activity-dependent plasticity at baroafferent synapses. Journal of Neurochemistry 108: 450-464.

L.Tarsa & A.Balkowiec (2009). Nerve growth factor regulates synaptophysin expression in developing trigeminal ganglion neurons in vitro. Neuropeptides 43: 47-52.

H.L.Scanlin, E.A.Carroll, V.K.Jenkins & A.Balkowiec (2008). Endomorphin-2 is released from newborn rat primary sensory neurons in a frequency- and calcium-dependent manner. European Journal of Neuroscience 27: 2629-2642.

I.Buldyrev, N.M.Tanner, H.Hsieh, E.G.Dodd, L.T.Nguyen & A.Balkowiec (2006). Calcitonin gene-related peptide enhances release of native brain-derived neurotrophic factor from trigeminal ganglion neurons. Journal of Neurochemistry 99: 1338-1350.