2016
DOI: 10.1523/jneurosci.3547-15.2016
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Neonatal Tissue Damage Promotes Spike Timing-Dependent Synaptic Long-Term Potentiation in Adult Spinal Projection Neurons

Abstract: Mounting evidence from both humans and rodents suggests that tissue damage during the neonatal period can "prime" developing nociceptive pathways such that a subsequent injury during adulthood causes an exacerbated degree of pain hypersensitivity. However, the cellular and molecular mechanisms that underlie this priming effect remain poorly understood. Here, we demonstrate that neonatal surgical injury relaxes the timing rules governing long-term potentiation (LTP) at mouse primary afferent synapses onto matur… Show more

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Cited by 35 publications
(51 citation statements)
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“…It should also be noted that aberrant sensory input resulting from injury during the early postnatal period can have prolonged consequences for central nociceptive processing, including (but not limited to) a disruption in the balance between excitatory and inhibitory synaptic transmission and a facilitation of synaptic long-term potentiation (LTP) in the spinal dorsal horn [40,41], elevated spinal neuroimmune responses [4,67], heightened opioidergic tone in the brain [34,35] and changes in descending inhibitory pathways [68,76]. This highlights the need for future studies examining the effects of early life VNC exposure on the functional organization of developing pain networks within the CNS.…”
Section: Discussionmentioning
confidence: 99%
“…It should also be noted that aberrant sensory input resulting from injury during the early postnatal period can have prolonged consequences for central nociceptive processing, including (but not limited to) a disruption in the balance between excitatory and inhibitory synaptic transmission and a facilitation of synaptic long-term potentiation (LTP) in the spinal dorsal horn [40,41], elevated spinal neuroimmune responses [4,67], heightened opioidergic tone in the brain [34,35] and changes in descending inhibitory pathways [68,76]. This highlights the need for future studies examining the effects of early life VNC exposure on the functional organization of developing pain networks within the CNS.…”
Section: Discussionmentioning
confidence: 99%
“…To address this issue, a recent study [ 69 ] evoked action potential firing in lamina I projection neurons at defined intervals either before (i.e., Post → Pre) or after (Pre → Post) the arrival of a presynaptic input mediated by sensory afferents (with the pairing protocol repeated 30 times at 0.2 Hz). The resultant change in synaptic strength was measured and compared between adult mice that had experienced surgical injury as a neonate and naïve littermate controls.…”
Section: Neonatal Injury Relaxes the Timing Rules Governing Spike mentioning
confidence: 99%
“…In projection neurons from naïve mice, Pre → Post pairings at an interval between 10–20 ms produced significant t-LTP, while the reverse (i.e., Post → Pre) pairings failed to change the amplitude of the synaptic response (i.e., produced neither t-LTP nor t-LTD). Strikingly, hindpaw incision at P3 significantly widened the timing window for evoking t-LTP ( Figure 1 ), as a greater potentiation of excitatory postsynaptic current (EPSC) amplitude was seen in projection neurons from these mice at Pre → Post intervals of 20 and 50 ms compared to the naïve group [ 69 ]. In addition, reverse (i.e., Post → Pre) pairings produced marked t-LTP in neonatally-injured mice, suggesting that early tissue damage removes the temporal requirement for the sensory input to precede the firing of adult projection neurons.…”
Section: Neonatal Injury Relaxes the Timing Rules Governing Spike mentioning
confidence: 99%
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“…[110] In addition, prior neonatal incision alters the temporal requirements for long-term potentiation at primary afferent synapses onto adult lamina I projection neurons, unmasks a role of calcium-permeable AMPA receptors, and thus predisposes to enhanced response to subsequent injury. [108] Prolonged afferent blockade prior to neonatal incision (bupivacaine hydrochloride powder or tetrodotoxin microcapillaries implanted adjacent to sciatic nerve) prevented the increase in glutamatergic miniature excitatory postsynaptic currents (mEPSCs) following incision at P3 but not older ages, [111] again highlighting the vulnerability of neonatal spinal nociceptive circuits to activitydependent change.…”
Section: Spinal Cord Synaptic Functionmentioning
confidence: 99%