Rapid adaptation to Elevated Extracellular Potassium in the Pyloric Circuit of the Crab, Cancer borealis

Abstract

<jats:title>Abstract</jats:title><jats:p>Elevated [K<jats:sup>+</jats:sup>] is often used to alter excitability in neurons and networks by shifting the potassium equilibrium potential (E<jats:sub>K</jats:sub>) and, consequently, the resting membrane potential. We studied the effects of increased extracellular [K<jats:sup>+</jats:sup>] on the well-described pyloric circuit of the crab, <jats:italic>Cancer borealis.</jats:italic> A 2.5-fold increase in extracellular [K<jats:sup>+</jats:sup>] (2.5x[K<jats:sup>+</jats:sup>]) depolarized Pyloric Dilator (PD) neurons and resulted in short-term loss of their normal bursting activity. This period of silence was followed within 5-10 minutes by the recovery of spiking and/or bursting activity during continued superfusion of 2.5x[K<jats:sup>+</jats:sup>] saline. In contrast, when PD neurons were pharmacologically isolated from pyloric presynaptic inputs, they exhibited no transient loss of spiking activity in 2.5x[K<jats:sup>+</jats:sup>], suggesting the presence of an acute inhibitory effect mediated by circuit interactions. Action potential threshold in PD neurons hyperpolarized during an hour-long exposure to 2.5x[K<jats:sup>+</jats:sup>] concurrent with the recovery of spiking and/or bursting activity. Thus, the initial loss of activity appears to be mediated by synaptic interactions within the network, but the secondary adaptation depends on changes in the intrinsic excitability of the pacemaker neurons. The complex sequence of events in the responses of pyloric neurons to elevated [K<jats:sup>+</jats:sup>] demonstrates that electrophysiological recordings are necessary to determine both the transient and longer-term effects of even modest alterations of K<jats:sup>+</jats:sup> concentrations on neuronal activity.</jats:p><jats:sec><jats:title>Significance Statement</jats:title><jats:p>Solutions with elevated extracellular potassium are commonly used as a depolarizing stimulus. Moreover, hyperkalemia is associated with a number of disease states, including epileptic seizures and brain traumas. We studied the effects of high [K<jats:sup>+</jats:sup>] saline on the well-described pyloric circuit of the crab stomatogastric ganglion. A 2.5-fold increase in extracellular [K<jats:sup>+</jats:sup>] led to a transient loss of activity in pyloric neurons that was not due to depolarization block. This was followed by a rapid increase in excitability and concurrent recovery of spiking and rhythmic bursting activity within minutes. These results suggest that effects of high [K<jats:sup>+</jats:sup>] on neuronal circuits can be complex and non-stationary.</jats:p></jats:sec>

Mapping circuit dynamics during function and dysfunction

“…We observed that high pH (>9.5) did not silence the preparation, but silent states were observed in low pH (<6.5), consistent with previously published manual annotation of this data (Haley et al, 2018). Silent states were also observed in 2.5 × [ K + ], as reported earlier by He et al (2020). Previous work has shown that the isolated pacemaker kernel (AB and PD neurons) has a stereotyped trajectory from bursting through tonic spiking to silence when subjected to temperature and high [ K + ] perturbations (Ratliff et al, 2021).…”

“…What remains unclear is if extreme perturbations of different modalities share common pathways of destabilizing and disrupting the pyloric rhythm (Ratliff et al, 2021). In principle, these environmental perturbations can disrupt neuron and circuit function in qualitatively different ways: e.g., changes in extracellular potassium concentration can alter the reversal potential of potassium (He et al, 2020) vs. changes in temperature can have varied effects on the timescales and conductances of all ion channels (Tang et al, 2010; Caplan et al, 2014). Because prior work was focussed on studying the limits of robustness, and lacked a detailed quantitative description of irregular behavior, the fine structure of the transition between functional dynamics and silent or “crashed” states remain poorly characterized (Ratliff et al, 2021).…”

“…Some perturbations like decentralization can have complex, time varying and variable effects, because neurons in the STG are multiply modulated (Marder, 2012); this may lead to the complex and diverse responses seen on decentralization (Figure 7). Others like changing extracellular [ K + ] can have more focussed effects, which changes the reversal potential of K + ions, altering currents through K + permeable ion channels, and tends to depolarize neurons (He et al, 2020). The challenge in interpreting data from experiments with perturbations such as these is the dual complexity of the elicited circuit behavior and the functional effects of the perturbations.…”

“…Temperature was controlled as described in Tang et al (2012, 2010); Haddad and Marder (2018). Extracellular potassium concentrations were varied as described in He et al (2020). pH perturbations are described in Haley et al (2018).…”

A model of rapid homeostatic plasticity accounts for hidden, long-lasting changes in a neuronal circuit after exposure to high potassium

“…The crustacean stomatogastric ganglion (STG) is an excellent model system in which to study underlying network dynamics and mechanisms of circuit robustness both through recording from well-studied identified neurons and computational models of those neurons 33,[35][36][37][38] . Importantly, the physiological behavior of each neuron within the STG is relatively stereotyped, allowing us to determine whether a given pattern of activity is normal.…”