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|Professor and Assistant Dean for Admissions, College of Medicine|
|Office: 103 Block Health Science Building|
|Fax: 419-383- 3008|
1975 B.S. Biology - Bowling Green State University , Bowling Green , Ohio .
My current research interests are in the field of developmental neurobiology and neuroplasticity. I have two principle interests both of which are involved with the formation and plasticity of highly organized sensory pathways. For the past twelve years my laboratory has been studying the anatomical and functional reorganization of the rat dorsal column/medial lemniscal pathway in response to the loss of a forelimb at birth. By examining this pathway at multiple levels ie., brainstem, thalamus, and cortex, we have shown that major subcortical anatomical and functional reorganization occurs in the brainstem. These changes are only observable in the primary somatosensory cortex when ? -amino butyric acid (GABA) receptors are blocked. The key feature of the functional reorganization observed subcortically and in the cortex after GABA receptor blockade is neurons with receptive fields that include both the forelimb stump and hindlimb (split Rfs) in regions where only the forelimb would normally be present. Future experiments will address questions regarding the conditions necessary for the reorganization and the mechanism of cortical suppression of sensory information observed after neonatal forelimb removal in the rat. We employ a wide range of both physiological and anatomical methods to answer these questions.
Figure 1. Schematic illustrating the somatosensory pathway reorganization that occurs in rats that loose a forelimb at birth. Primary afferents from the sciatic nerve that normally innervate the gracile nucleus (GN) also invade the cuneate nucleus (CN). Approximately 40% of the neurons in the CN on the affected side express split-Rfs (responsive to both stump and hindlimb cutaneous stimulation). The percentage of split-Rfs detectable at the level of the stump region of the ventroposterior thalamus is reduced to19% and further reduced to 4% in the SI stump representation. Under GRB the percentage of split-Rfs in the SI stump region increases to approximately 35%. The hindlimb component of the SI stump split-Rfs arises from the SI hindlimb cortex and projects to the SI forelimb-stump representation via a polysynaptic pathway through the dysgranular cortex.
Figure 2. Circuit model depicting the major inputs to a split-Rf expressing neuron (labeled s) in the SI forelimb-stump representation of a neonatally amputated rat. Thalamocortical axons project from the VPL to layer IV of SI. Ascending hindlimb information excites layer IV neurons. This excitation spreads vertically to supra- and/or infragranular neurons, and then horizontally, via polysynaptic circuits through dysgranular cortex, to neurons in the deprived SI forelimb-stump representation (yellow dashed arrows). The split-Rf neurons in the stump representation receive subcortical input from the stump via the VPL and the hindlimb information via an intracortical projection from the ipsilateral hindlimb representation. Inhibitory synapses of GABAergic interneurons (red) positioned close to the split-Rf neurons selectively suppress the hindlimb input to these cells under normal conditions.
Myother more recent interest is to understand the ability of somatosensory thalamic axons to grow into the cortex and distribute themselves in a highly organized topographical pattern corresponding to the body surface. We wish to learn what factors influence the morphology and distribution of developing individual thalamocortical axons. Our previous studies have shown that developing thalamocortical axons transiently express both serotonin 1B receptors and the serotonin transporter, and that elevating or decreasing serotonin levels in the developing cortex markedly alters the organization of thalamocortical afferents related to the mystacial vibrissae. Current research is focusing of the role of Eph receptors and Ephrin ligands in the postnatal development of the somatosensory cortex. Future experiments will be directed toward determining the source of these receptors and ligands as well as modulating their express to determine their influence on the organization of thalamocortical axons.
Figure 3. A . Photomicrograph of a section through the center of the PMBSF of a normal P8 rat stained with an antibody specific for the EphA5 receptor. Areas of high immunoreactivity conform to a vibrissae-like distribution with intervening areas of reduced immunostaining corresponding to the septal regions of the barrelfield.
B. No vibrissae-like immunoreactivity pattern is evident when the primary antibody was omitted during processing. Scale bar equals 500 mm.
Figure 4. A. Flattened tangential section through layer IV of the PMBSF taken from a P8 rat showing ephrin-A2 immunoreactivity arrayed in a barrel pattern. Note the reduced immunoreactivity in the interbarrel septa.B. Coronal section through VPM of a P8 rat showing ephrin-A2 immunoreactivity in this nucleus. Note the reduced immunoreactivity in the adjacent POm region. C. Flattened tangential section through layer IV of S-I taken from a P8 rat showing ISH with a riboprobe complementary to ephrin-A2 mRNA. Note the reduced signal for this probe within the PMBSF and a marked increase in the hybridization signal (arrows) in the region of the PMBSF border. D. ISH staining with the ephrin-A2 riboprobe in a coronal section through VPM showing a strong hybridization signal within this nucleus and a marked reduction of staining in the adjacent POm region. Scale bar equals 750 µm.
|Electrophysiology, Anterograde and retrograde fiber labeling techniques, Immunohistochemistry, Western blots, Production and application of polyclonal and monoclonal antibodies, In situ hybridization, Antisense silencing of gene expression, Tissue culture techniques,|
Stojic, A.S., Lane, R.D., Killackey, H.P. and Rhoades, R.W. -2000- Suppression of Hindlimb Inputs to S-I Forelimb-Stump Representation of Rats with Neonatal Forelimb Removal: GABA Receptor Blockade and Single Cell Responses. J. Neurophys. 83:3377-3387.
Young-Davies, C.L., Bennett-Clarke, C.A., Lane, R.D. and Rhoades, R.W. -2000- Selective Facilitation of the Serotonin (1B) Receptor Causes Disorganization of Thalamic Afferents and Barrels in Somatosensory Cortex of Rat. J. Comp. Neurol. 425:130-138.
Stojic, A.S., Lane, R.D. and Rhoades, R.W. -2001- Intracortical Pathway Involving Dysgranular Cortex Conveys Hindlimb Inputs to the S-I Forelimb-Stump Representation of Neonatally Amputated Rats. J. Neurophys. 85:407-413.
Lane, R.D., Rizk, T., Chiaia, N.L., Mooney, R.D. and Rhoades, R.W. -2002- Effects of Alterations of the Vibrissae-Related Organization of Thalamocortical Axons upon the Organization and Outgrowth of Intracortical Connections in the Barrelfield of the Rat. Somatosen. Mot. Res. 19:125-129.
Kesterson, K,L., Lane, R.D. and Rhoades, R.W. -2002- Effects of Elevated Serotonin Levels on Patterns of GAP-43 Expression During Barrel Development in Rat Somatosensory Cortex. Brain Res. Dev. Brain Res. 139:167-174.
Bowlus, T.H., Lane, R.D., Stojic, A.S., Johnston , M., Pluto, C.P., Chan, M., Chiaia, N.L.and Rhoades, R.W. -2003- Comparison of Reorganization on the Somatosensory System in Rats that Sustained Forelimb Removal as Neonates and as Adults. J.Comp. Neurol. 465:335-348.
Pluto, C.P., Lane, R.D., Chiaia, N.L., Stojic, A.S. and Rhoades, R.W. -2003- Role of Development in Reorganization of the SI Forelimb-Stump Representation in Fetally, Neonatally, and Adult Amputated Rats. J. Neurophys. 90:1842-1851.
Pluto CP, Lane RD, Rhoades RW. -2004- Local GABA Receptor Blockade Reveals Hindlimb Responses in the SI Forelimb-Stump Representation of Neonatally Amputated Rats. J Neurophysiol. 92:372-379.
Pluto CP, Chiaia NL, Rhoades RW, Lane RD. -2005- Reducing contralateral SI activity reveals hindlimb receptive fields in the SI forelimb-stump representation of neonatally amputated rats. J Neurophysiol. 94:1727-1732.
Lane RD , Chiaia NL, Kesterson KL, Rhoades RW, Mooney RD. -2006- Boundary-limited serotonergic influences on pattern organization in rat sensory cortex. Neurosci Lett. 395:165-169.