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.
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.
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