The postnatal reorganization of primary afferent input and dorsal horn cell receptive fields in the rat spinal cord is an activity-dependent process.
The dorsal horn of the spinal cord in the newborn rat is characterized by large cutaneous mechanoreceptive fields, a predominance of A-fibre synaptic inputs and diffuse primary afferent A-fibre projections, all of which are gradually reduced and refined over the first postnatal weeks. This may be partly responsible for the reduction in cutaneous flexion reflex sensitivity of rats over the postnatal period. Here we show that chronic, local exposure of the dorsal horn of the lumbar spinal cord to the NMDA antagonist MK801 from birth prevents the normal functional and structural reorganization of A-fibre connections. Dorsal horn cells in spinal MK801-treated animals, investigated at eight weeks of age by in vivo electrophysiological recording, had significantly larger cutaneous mechanoreceptive fields and greater A-fibre evoked responses than vehicle controls. C-fibre evoked responses were unaffected. Chronic MK801 also prevented the normal structural reorganization of A-fibre terminals in the spinal cord. The postnatal withdrawal of superficially projecting A-fibre primary afferents to deeper laminae did not occur in treated animals although C-fibre afferent terminals and cell density in the dorsal horn were apparently unaffected. Spinal MK801-treated animals also had significantly reduced behavioural reflex thresholds to mechanical stimulation of the hindpaw compared to naïve and vehicle-treated animals, whereas noxious heat thresholds remained unaffected. The results indicate that the normal postnatal structural and functional development of A-fibre sensory connectivity within the spinal cord is an activity-dependent process requiring NMDA receptor activation.
Beggs
Simon
S
Department of Anatomy and Developmental Biology, University College London, Gower Street, London WC1E 6BT, United Kingdom.
Torsney
Carole
C
Drew
Liam J
LJ
Fitzgerald
Maria
M
D000344:Afferent Pathways / Q000187:drug effects / Q000254:growth & development / Q000502:physiology; D000818:Animals; D000831:Animals, Newborn; D003692:Delayed-Action Preparations; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D004594:Electrophysiology; D005073:Evoked Potentials, Somatosensory / Q000502:physiology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D007150:Immunohistochemistry; D016202:N-Methylaspartate / Q000037:antagonists & inhibitors; D036421:Nerve Fibers, Unmyelinated / Q000187:drug effects / Q000502:physiology; D009473:Neuronal Plasticity; D011145:Polyvinyls; D020671:Posterior Horn Cells / Q000187:drug effects / Q000254:growth & development* / Q000502:physiology; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology*; D013116:Spinal Cord / Q000187:drug effects / Q000254:growth & development* / Q000502:physiology; D013997:Time Factors
D003692:Delayed-Action Preparations; D018691:Excitatory Amino Acid Antagonists; D011145:Polyvinyls; D016194:Receptors, N-Methyl-D-Aspartate; C016438:ethylenevinylacetate copolymer; D016202:N-Methylaspartate; D016291:Dizocilpine Maleate