| Summary: | In order to understand molecular mechanisms of neural plasticity, habituation of a simple neural circuit in Drosophila melanogester was investigated. A resistance reflex controlling the femoro-tibial joint angle was identified using electromyogram recording from the tibial extensor muscle. It was shown that typically only one of the two motor neurons innervating the muscle, the slow tibial extensor (SETi), was activated in the reflex response. By targeting the expression of tetanus toxin, which cleaves synaptobrevin and blocks evoked synaptic transmission, to the sensory neurons in the femoral chordotonal organ (feCO) using P (Ga14) insertion lines, it was demonstrated that the feCO was necessary for the resistance reflex. Upon repetitive stimulation of the sensory neurons, the strength of the reflex response decreased. This response decrement conformed to parametric features of habituation: exponential decay, stimulus amplitude and frequency dependent, spontaneous recovery, and dishabituation. Ca$\sp{2+}$/calmodulin-dependent protein kinase II (CaMKII) has been implicated in synaptic plasticity and learning. To test the role of the different activity states of CaMKII in habituation, transgenes coding for an inhibitory peptide of the kinase, a CaMKII subunit incapable of becoming Ca$\sp{2+}$-independent, and a constitutively active kinase was expressed selectively in the presynaptic sensory neurons using a P (Ga14) insertion line. Expression of a Ca$\sp{2+}$-independent form of CaMKII in the sensory neurons increased reflex response and blocked habituation. When a kinase incapable of becoming Ca$\sp{2+}$-independent was expressed in the sensory neurons, the initial reflex response during a habituation trial was reduced and habituation of the reflex was nearly blocked. When the inhibitory peptide was expressed in the sensory neurons, the reflex response was decreased and habituation was also blocked. These results suggested that the Ca$\sp{2+}$-independent CaMKII sets the response level of the neural circuit, allowing the circuit to exhibit appropriate dynamics, and an optimal level of CaMKII in the presynaptic neuron is required for the reflex to show habituation. This system now can be used to dissect the molecular cascade involved in habituation and other forms of neural plasticity.
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