Impact of cell-intrinsic plasticity on the neuronal control of behavior

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Behavioral responses to sensory stimuli change in a flexible way depending on both internal and external factors, including previous experience and stimulation types. Even simple organisms like the medicinal leech feature activity-dependent changes in neuronal and behavioral responses. The cellular basis of stimulus avoidance behaviors can be studied well in in a semi-intact preparation consisting of one leech ganglion and a piece of the body wall. Light touch usually causes the body wall to bend away locally, and sometimes even swimming. These behavioral responses are controlled by subsets of the 400 experimentally accessible, individually characterized neurons in the ganglion. Our previous studies suggest that T (touch) cells, the most sensitive mechanoreceptors, play a major role in eliciting behavioral responses to tactile stimulation. Moreover, we concluded that a T cell has at least one spike initiation zone for encoding tactile stimulation of the skin and one for processing synaptic inputs close to the soma. Furthermore, we identified a cell-intrinsic plasticity mechanism which alters spiking patterns depending on previous activity.To identify how cell-intrinsic plasticity influences the control of behavior, we plan to perform experiments in semi-intact body wall preparations. Simultaneously to intracellular T cell double recordings, we record the network activity with voltage-sensitive dyes and the muscle movement of the resulting behavior. In our “replay experiments”, tactile skin stimulation is alternated with the somatic current injection to the pair of T cells, eliciting exactly the same T cell spike trains as the preceding touch stimulus, without inducing activity of the other mechanoreceptors. Comparing the two conditions allows us to identify the impact of T cell spiking on network activity and behavioral responses. In addition to the steady-state with long recovery time between stimuli, we will perform the same analysis after massive T cell stimulation that causes cell-intrinsic plasticity. The project is structured into four sub-projects, guided by the following hypotheses:1. Cellular level: The interaction of cell-intrinsic plasticity mechanisms occurring at multiple spike-initiation zones causes a flexible shift in the relative impact of different computational tasks (i.e. sensory coding near the skin vs. synaptic integration near the cell body).2. Behavioral level: The relative spike timing of T cell pairs, which was shown to encode touch location, is decoded by the network to control local bending.3. Network level: When the skin is touched, T cell spikes first activate the preparatory network and later shape the local bending response.4. All levels: The activity-dependent flexibility of T cell responses drives behavioral flexibility.With these experiments, we identify the impact of cell-intrinsic plasticity on the neuronal control of behavior for the example of the leech.