Patterned and topographic organization of neural connections is an essential structural substrate for processing sensory information in the brain. The rodent trigeminal pathway is an exceptionally attractive model system to study the cellular and molecular mechanisms underlying the malleability of patterned somatotopic maps following peripheral sensory nerve damage. In this system, the patterned array of whiskers on the snout is represented by neural modules at every level in the brain. Injury to the whisker follicles or the sensory nerve innervating them during a critical period in development leads to irreversible and predictable structural alterations. Accompanying physiological plasticity is largely unknown. The major aim of this proposal is to uncover cellular and molecular mechanisms of neonatal peripheral nerve injury-induced CNS synaptic plasticity in the first- and second-order relay stations of the trigeminal sensory pathway. During the current funding period, we characterized synaptic plasticity within the trigeminal principal sensory nucleus following acute nerve injury in neonates. We found that peripheral denervation induces rapid synaptic plasticity, now we propose to compare its manifestations following successful peripheral nerve regeneration in its thalamic relay station, ventroposteromedial nucleus. The long-term objective of this proposal is to determine cellular mechanisms underlying peripheral nerve injury-induced plasticity along the central somatosensory pathways in neonates. Combined electrophysiological, pharmacological and anatomical techniques will be used to chart out membrane properties, synaptic responses, and NMDA receptor-mediated response characteristics in the trigeminal brainstem and thalamus. A solid understanding of mechanisms underlying development of patterned neural organization and its plasticity following peripheral nerve injury is critical for preventing or repairing often irreversible effect of damage to the developing human nervous system.

Public Health Relevance

This research proposal aims to uncover manifestations and mechanisms of central nervous system plasticity following peripheral sensory nerve injury in neonates. We use the rodent trigeminal system as a model, because much is known about the organization and function of this system. Availability of genetically engineered mice to study molecular loss-of-function also makes this system highly attractive. This proposal is geared towards understanding cellular and molecular mechanisms of neural plasticity in the brain following peripheral nerve injury.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Research Project (R01)
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Special Emphasis Panel (ZRG1-IFCN-F (02))
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Riddle, Robert D
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University of Maryland Baltimore
Anatomy/Cell Biology
Schools of Medicine
United States
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Erzurumlu, Reha S (2016) CNS consequences of perinatal peripheral injuries. Exp Neurol 275 Pt 2:243-4
Tsytsarev, Vassiliy; Pumbo, Elena; Tang, Qinggong et al. (2016) Study of the cortical representation of whisker frequency selectivity using voltage-sensitive dye optical imaging. Intravital 5:e1142637
Lo, Fu-Sun; Erzurumlu, Reha S (2016) Sensory Activity-Dependent and Sensory Activity-Independent Properties of the Developing Rodent Trigeminal Principal Nucleus. Dev Neurosci 38:163-170
Suzuki, A; Lee, L-J; Hayashi, Y et al. (2015) Thalamic adenylyl cyclase 1 is required for barrel formation in the somatosensory cortex. Neuroscience 290:518-29
Lo, Fu-Sun; Zhao, Shuxin; Erzurumlu, Reha S (2014) Neonatal infraorbital nerve crush-induced CNS synaptic plasticity and functional recovery. J Neurophysiol 111:1590-600
Arakawa, Hiroyuki; Suzuki, Ayumi; Zhao, Shuxin et al. (2014) Thalamic NMDA receptor function is necessary for patterning of the thalamocortical somatosensory map and for sensorimotor behaviors. J Neurosci 34:12001-14
Kivrak, Beril G; Erzurumlu, Reha S (2013) Development of the principal nucleus trigeminal lemniscal projections in the mouse. J Comp Neurol 521:299-311
Mirza, Rusella; Kivrak, Beril G; Erzurumlu, Reha S (2013) Cooperative slit and netrin signaling in contralateralization of the mouse trigeminothalamic pathway. J Comp Neurol 521:312-25
Erzurumlu, Reha S; Gaspar, Patricia (2012) Development and critical period plasticity of the barrel cortex. Eur J Neurosci 35:1540-53
Lo, Fu-Sun; Zhao, Shuxin; Erzurumlu, Reha S (2011) Astrocytes promote peripheral nerve injury-induced reactive synaptogenesis in the neonatal CNS. J Neurophysiol 106:2876-87

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