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Ana Solodkin, Ph.D.

Senior Anatomist
Assistant Professor in Anatomy & Neurobiology

I began my research career as an undergraduate student at Anahuac University in Mexico City, studying psychophysiology and performing research on plasticity during REM sleep and graduating as Suma Cum Laude. In 1988, I entered graduate school at the "Center for Research and Advanced Studies of the National Polytechnic Institute" (CINVESTAV) in Mexico City, where I began my doctoral studies with Dr. Pablo Rudomin in the area of presynaptic inhibition, publishing several papers on long term plasticity in the spinal cord. With an aim toward investigating mechanisms of neuronal plasticity and the neuropharmacology of serotonin, I was invited to Bethesda to continue my studies at the NIH under Dr. M.A. Ruda. It was at the NIH that I completed my Ph.D. dissertation in plastic changes in the spinal cord after capsaicin application in the neonatal rat.

Immediately after completing my Ph.D. in Physiology and Biophysics in 1991, I moved to the University of Iowa to pursue post-doctoral training. I joined the Cognitive Neurology group under the direction of Dr. Antonio Damasio receiving direct training with Dr. Gary van Hoesen in the area of human neuroanatomy, especially in reference to limbic lobe anatomy. With Paul Broca's historical understanding of the importance of the "limbic lobe", the modern study of memory, emotion, and attention has focused on this part of the brain. My post-doctoral work concentrated on one of the limbic structures, the entorhinal cortex (Brodmann's area 28). This is an area of particular importance because it is one of the first structures affected in Alzheimer's Disease (AD) and because the neurons exhibiting pathological alterations (such as neurofibrillary tangles) are for the most part projection neurons responsible for interconnections between the entorhinal cortex and the hippocampal formation and other association areas. During these post-doctoral years, I published a number of papers in prominent Journals on the pathological alterations in these structures. One important result, originally postulated by Dr. Van Hoesen and further elaborated with my work, was that the changes in the reciprocal connectivity between these structures in AD results in a de-afferentation and de-efferentation of the hippocampus from the cortex. This "functional isolation" of the hippocampus through the destruction of the entorhinal cortex could be, at least in part, the structural basis for some of the memory and emotional deficits of AD.

The theoretical considerations behind these studies were based on Klinger's work (1948, Bard,Abh. 1, Gebueder Fretz. Ag. Zurich), who suggested, based on the gross appearance of the brain, a possible modular organization of the entorhinal cortex, similar to the modular organization described later in sensory and motor cortices. The technical aspects of my post-doctoral work focused on the cyto- and chemoarchitectural description of the vertical-modular organization of the entorhinal and perirhinal cortices in man. This work involved human tissue and employed a number of anatomical methods, ranging from classical histochemical staining (Gallyas, thioflavine-S, Congo red), enzymatic histochemistry (AChE, NADPH-d) to immunohistochemistry for a variety of neurotransmitters and modulators (substance P; NPY; somatostatin-28; CGRP), enzymes (GAD, glutaminase), proteins (neurofilaments, collagen, Ca2+-binding proteins), as well as neuropathological markers (Alz-50, 10D5). By gaining expertise in methods involving human tissue, I thus complemented my previous technical experience in animal model systems. But more importantly, I was introduced to human cortical neuroanatomy in one hand and applied science, in particular, in the area of Cognitive Neurology.

From my initial work in an animal model system addressing issues of plasticity and synaptic habituation to the study of human cortical anatomy in dementia, my active and long term research has focused on the relationship between basic neurobiology and cognitive neurology. To accomplish this goal however, I realized that the anatomical assessment albeit very informative, lacked a direct physiological correlation. Hence, when I moved to Maryland, I decided to complete my scientific approach by adding functional Magnetic Resonance Imaging (fMRI) to my studies of human neuroanatomy. I started working then in close collaboration with one of the leaders in this area, Dr. Steven Small who introduced me to fMRI and to vascular disease, especially ischemic stroke. The study of rehabilitation after ischemic stroke proved to be a wonderful model for cortical plasticity since unlike Alzheimer's disease, stroke patients can at least in part, recover over time.

My aim with this work has been to discover anatomical and physiological substrates of disease that have a reasonable likelihood of leading to therapeutic interventions. My present interest on recovery after focal ischemic damage builds on my previous work in three ways: (1) integrating previous areas of investigation, including CNS plasticity, cortical circuit analysis, serotonergic pharmacology, and human frontotemporal anatomy, into a coherent program of clinically relevant basic scientific study; (2) applying the neurological localizational method to study the most prevalent of all causes of disability (especially in the population over 65 years).

Selected Publications

Solodkin A. and Rudomin, P. (1983) Activation of brain-stem serotoninergic pathways decrease homosynaptic depression of monosynaptic responses of frog spinal motoneurons. Brain Res. 280:373-378.

Solodkin, M., Cardona, A. and Corsi-Cabrera, M. (1985) Paradoxical sleep augmentation after imprinting in the domestic chick. Physiol. Behav. 35:343-348.

Traub, R.J., Solodkin, A. and Ruda, M.A. (1989) Calcitonin gene-related peptide immunoreactivity in the cat lumbosacral spinal cord and the effects of multiple dorsal rhizotomies. J. Comp. Neurol. 287:225-237.

Noguchi, K., Kowalski, K., Traub, R.J., Solodkin, A., Iadarola, M.J. and Ruda, M.A. (1991) Dynorphin expression and Fos-like immunoreactivity following inflammation induced hyperalgesia are colocalized in spinal cord neurons. Mol. Brain Res. 10:227-233.

Solodkin, A., Traub, R.J. and Gebhart, G.F. (1992) Unilateral hind paw inflammation produces bilateral increase in NADPH-diaphorase activity in the rat lumbar spinal cord. Neuroscience 51:495-499.

Van Hoesen G.W. and Solodkin A. (1993) Some modular features of temporal cortex in humans as revealed by pathological changes in Alzheimer's disease. Cerebral Cortex 3:465-475.

Traub, R.J., Solodkin, A. and Gebhart, G.F. (1994) NADPH-diaphorase histochemistry provides evidence for a bilateral, somatotopically inappropriate response to unilateral hindpaw inflammation in the rat. Brain Res. 647:113-123

Van Hoesen G.W. and Solodkin A. (1994) Cellular and systems neuroanatomical changes in Alzheimer's disease. In: Calcium hypothesis of aging and dementia. Disterhoft J.F. and Khachaturian Z.S. (eds). Proc NY Acad Sci (USA) 747:12-35.

Traub, R.J., Solodkin, A., Meller, S.T. and Gebhart, G.F. (1994) Spinal cord NADPH-diaphorase histochemical staining but not nitric oxide synthase immunoreactivity increases following carrageenan-produced hindpaw inflammation in the rat. Brain Res. 668:204-210.

Traub, R.J., Silva, E., Gebhart, G.F. and Solodkin, A. (1996) Noxious colorectal distention induced c-Fos protein in limbic brain structures in the rat. Neurosci. Lett. 215: 165-168

Solodkin, A., and Van Hoesen, G.W. (1996) Entorhinal cortex modules of the human brain. J. Comp. Neurol. 365(4):610-627.

Solodkin, A., Veldhuizen S.D. and Van Hoesen, G.W. (1996) The viability and vulnerability of parvalbumin-containing neurons in the entorhinal cortex in Alzheimer disease. J Neurosci. 16: 3311-3321.

Reed, LA; Grabowski, TJ; Schmidt, ML; Solodkin, A; Goat, A; Van Hoesen, GW; Schelper, RL and Trojanowski, JQ. (1997) Autosomal dominant dementia with widespread neurofibrillary tangles. Ann. Neurol. 42: 564-572.

Lidow MS and Solodkin A (1997) Use of the cyclone Storage Phosphor System for rapid development of a receptor autoradiographic assay. Tools and Techniques, 22: pp4.

Small SL and Solodkin A (1998) Neurobiology of stroke rehabilitation. The Neuroscientist, 4, 426-434

Solodkin, A; Hlustik, P; Noll DC and Small SL (2000) Lateralization of Motor Circuits and Handedness during Finger Movements Neurology (in press)

Hlustik P; Solodkin, A; Gullapalli R; Noll DC and Small SL (2000) Somatotopy of the human primary motor and sensory hand areas revisited Cerebral Cortex (in press)