Maintenance of Modality-specific Connections in the Spinal Cord after Neonatal Nerve Growth Factor Deprivation

Authors

  • Gary R. Lewin,

    Corresponding author
    1. Department of Neurobiology and Behavior, State University of New York at Stony Brook, Stony Brook, NY 11794, USA
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    • 1

      Growth Factors and Regeneration Group, Max Delbrück Centre for Molecular Medicine, Robert-Rössle-Strasse 10, Berlin-Buch D-13122, Germany

  • Lorne M. Mendell

    1. Department of Neurobiology and Behavior, State University of New York at Stony Brook, Stony Brook, NY 11794, USA
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Gary R. Lewin, Growth Factors and Regeneration Group, Max-Delbrück-Centrum for Molecular Medicine, Robert-Rössle-Strasse 10, Berlin-Buch D-13122, Germany

Abstract

We have investigated the properties of antidromically identified lamina I neurons in the rat dorsal horn (in vivo) after neonatal administration of antibody to nerve growth factor (anti-NGF). Treatment from postnatal day (P) 2 to P9 yielded normal lamina I cell physiology; most cells responded to mechanical nociception and the remainder had a wide dynamic range (WDR). Extending anti-NGF treatment to P14 reduced the proportion of cells responding to mechanical nociception, increased the proportion of WDR cells, and caused the emergence of cells not driven by cutaneous inputs. Both nociceptive-specific and WDR cells had larger receptive fields, suggestive of enhanced central action of the remaining nociceptive afferents. These findings cannot be explained by direct action of anti-NGF on spinal cord neurons since both P2-9 and P2-14 treatments should have had similar effects given the time course of development of the blood-brain barrier. The results are discussed in terms of previous findings indicating normal numbers of D-hairs and high-threshold mechanoreceptors (HTMRs) after anti-NGF treatment from P2 to P9, but a decline in the number of HTMRs and an increase in the number of D-hairs after treatment from P2 to P14. It is suggested that the reduction in nociceptive neurons and the appearance of neurons not driven by cutaneous stimulation in lamina I results from the reduction in HTMR input. However, D-hair input to lamina I did not increase despite the larger number of these afferents, suggesting that their central action was regulated to maintain appropriate modality relationships between periphery and centre.

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