Non-synaptic Plasticity in Leech Touch Cells

Abstract

The role of Na+/K+-pumps in activity-dependent synaptic plasticity has been described in both vertebrates and invertebrates. Here, we provide evidence that the Na+/K+-pump is also involved in activity-dependent non-synaptic cellular plasticity in leech sensory neurons. We show that the resting membrane potential (RMP) of T cells hyperpolarizes in response to repeated somatic current injection, while at the same time their spike count (SC) and the input resistance (IR) increase. Our Hodgkin–Huxley-type neuron model, adjusted to physiological T cell properties, suggests that repetitive action potential discharges lead to increased Na+/K+-pump activity, which then hyperpolarizes the RMP. In consequence, a slow, non-inactivating current decreases, which is presumably mediated by voltage-dependent, low-threshold potassium channels. Closing of these putative M-type channels due to hyperpolarization of the resting potential increases the IR of the cell, leading to a larger number of spikes. By this mechanism, the response behavior switches from rapidly to slowly adapting spiking. These changes in spiking behavior also effect other T cells on the same side of the ganglion, which are connected via a combination of electrical and chemical synapses. An increased SC in the presynaptic T cell results in larger postsynaptic responses (PRs) in the other T cells. However, when the number of elicited presynaptic spikes is kept constant, the PR does not change. These results suggest that T cells change their responses in an activity-dependent manner through non-synaptic rather than synaptic plasticity. These changes might act as a gain-control mechanism. Depending on the previous activity, this gain could scale the relative impacts of synaptic inputs from other mechanoreceptors, versus the spike responses to tactile skin stimulation. This multi-tasking ability, and its flexible adaptation to previous activity, might make the T cell a key player in a preparatory network, enabling the leech to perform fast behavioral reactions to skin stimulation.

Initial Variability and Time-Dependent Changes of Neuronal Response Features Are Cell-Type-Specific

“…That is, the more hyperpolarized these cells were, the larger number of spikes they generated. This finding is consistent with the results reported by Meiser et al, 2019 that T cells increase their spike count with hyperpolarization. However, it is contrary to standard expectations that a more hyperpolarized cell is further away from the spike threshold and therefore fires fewer spikes.…”

“…That is, the more the RMP hyperpolarized over time, the more strongly the spike count increased. This finding is consistent with the negative correlation between the initial values of spike count and RMP ( Figure 4A ), and with Meiser et al, 2019 . We observed the same tendency in P1 cells, even though this relationship was not significant.…”

“…While T3 and P1 cells increased their spike count, Rz cells did the opposite. In accordance with Meiser et al, 2019 , we found that the more the RMP of T3 cells hyperpolarized, the more these cells spiked. However, this negative correlation between the changes in RMP and spike count was only significant for T3 cells, but not for P1 cells.…”

“…Stimulation protocol (stim): To replicate our previous findings, we stimulated single T3, P1 or Rz cells with the stimulus protocol developed by Meiser et al (2019) . In brief, the stimulation has a total length of 30 s and consists of pseudo-randomized current pulses, varying in amplitude from −2 to + 1.5 nA, with a duration of 500 ms each, separated by 1,500 ms without current input ( Figure 1A ).…”

“…Recently, Meiser et al (2019) found that repeated somatic stimulation in T cells led to a hyperpolarization of the resting membrane potential over time in addition to an increased spike count. Modeling results suggested a two-step mechanism of short-term intrinsic plasticity: First, repeated stimulation leads to Na + influx and therefore to Na + /K + pump activation, slowly hyperpolarizing the resting membrane potential.…”