Modulation of excitability in Aplysia tail sensory neurons by tyrosine kinases

Tyrosine kinases have recently been shown to modulate synaptic plasticity a nd ion channel function. We show here that tyrosine kinases can also modula te both the baseline excitability state of Aplysia tail sensory neurons (SN s) as well as the excitability induced by the neuromodulator serotonin (5HT ). First, we examined the effects of increasing and decreasing tyrosine kin ase activity in the SNs. We found that tyrosine kinase inhibitors decrease baseline SN excitability in addition to attenuating the increase in excitab ility induced by 5HT. Conversely, functionally increasing cellular tyrosine kinase activity in the SNs by either inhibiting opposing tyrosine phosphat ase activity or by direct injection of an active tyrosine kinase (Src) indu ces increases in SN excitability in the absence of 5HT. Second, we examined the interaction between protein kinase A (PKA), which is known to mediate 5HT-induced excitability changes in the SNs, and tyrosine kinases, in the e nhancement of SN excitability. We found that the tyrosine kinases function downstream of PKA activation since tyrosine kinase inhibitors reduce excita bility induced by activators of PKA. Finally, we examined the role of tyros ine kinases in other forms of 5HT-induced plasticity in the SNs. We found t hat while tyrosine kinase inhibitors attenuate excitability produced by 5HT , they have no effect on short-term facilitation (STF) of the SN-motor neur on (MN) synapse induced by 5HT. Thus tyrosine kinases modulate different fo rms of SN plasticity independently. Such differential modulation would have important consequences for activity-dependent plasticity in a variety of n eural circuits.