The Journal of Neurophysiology Vol. 85 No. 6 June 2001, pp. 2398-2411
Copyright ©2001 by the American Physiological Society

Modulation of Excitability in Aplysia Tail Sensory Neurons by Tyrosine Kinases

 ¹Interdepartmental Neuroscience Program, Yale University, New Haven, Connecticut 06520; and  ²Department of Neurobiology and Behavior, University of California, Irvine, California 92697-4550

Purcell, Angela L. and Thomas J. Carew. Modulation of Excitability in Aplysia Tail Sensory Neurons by Tyrosine Kinases. J. Neurophysiol. 85: 2398-2411, 2001. Tyrosine kinases have recently been shown to modulate synaptic plasticity and ion channel function. We show here that tyrosine kinases can also modulate both the baseline excitability state of Aplysia tail sensory neurons (SNs) as well as the excitability induced by the neuromodulator serotonin (5HT). First, we examined the effects of increasing and decreasing tyrosine kinase activity in the SNs. We found that tyrosine kinase inhibitors decrease baseline SN excitability in addition to attenuating the increase in excitability induced by 5HT. Conversely, functionally increasing cellular tyrosine kinase activity in the SNs by either inhibiting opposing tyrosine phosphatase activity or by direct injection of an active tyrosine kinase (Src) induces 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 enhancement of SN excitability. We found that the tyrosine kinases function downstream of PKA activation since tyrosine kinase inhibitors reduce excitability induced by activators of PKA. Finally, we examined the role of tyrosine kinases in other forms of 5HT-induced plasticity in the SNs. We found that while tyrosine kinase inhibitors attenuate excitability produced by 5HT, they have no effect on short-term facilitation (STF) of the SN-motor neuron (MN) synapse induced by 5HT. Thus tyrosine kinases modulate different forms of SN plasticity independently. Such differential modulation would have important consequences for activity-dependent plasticity in a variety of neural circuits.