Activation of protein kinase A contributes to the expression but not the induction of long-term hyperexcitability caused by axotomy of Aplysia sensory neurons
Xg. Liao et al., Activation of protein kinase A contributes to the expression but not the induction of long-term hyperexcitability caused by axotomy of Aplysia sensory neurons, J NEUROSC, 19(4), 1999, pp. 1247-1256
Nociceptive sensory neurons (SNs) in Aplysia provide useful models to study
both memory and adaptive responses to nerve injury. Induction of long-term
memory in many species, including Aplysia, is thought to depend on activat
ion of cAMP-dependent protein kinase (PKA). Because Aplysia SNs display sim
ilar alterations in models of memory and after nerve injury, a plausible hy
pothesis is that axotomy triggers memory-like modifications by activating P
KA in damaged axons. The present study disproves this hypothesis. SN axotom
y was produced by (1) dissociation of somata from the ganglion [which is sh
own to induce long-term hyperexcitability (LTH)], (2) transection of neurit
es of dissociated SNs growing in vitro, or (3) peripheral nerve crush. Appl
ication of the competitive PKA inhibitor Rp-8-CPT-cAMPS at the time of axot
omy failed to alter the induction of LTH by each form of axotomy, although
the inhibitor antagonized hyperexcitability produced by 5-HT application. S
trong activation of PKA in the nerve by coapplication of a membrane-permean
t analog of cAMP and a phosphodiesterase inhibitor was not sufficient to in
duce LTH of either the SN somata or axons. Furthermore, nerve crush failed
to activate axonal PKA or stimulate its retrograde transport. Therefore, PK
A activation plays little if any role in the induction of LTH by axotomy. H
owever, the expression of LTH was reduced by intracellular injection of the
highly specific PKA inhibitor PKI several days after nerve crush. This sug
gests that long-lasting activation of PKA in or near the soma contributes t
o the maintenance of long-term modifications produced by nerve injury.