Neuropeptide Modulation Increases Dendritic Electrical Spread to Restore Neuronal Activity Disrupted by Temperature

Abstract

Peptide neuromodulation has been implicated to shield neuronal activity from acute temperature changes that can otherwise lead to loss of motor control or failure of vital behaviors. However, the cellular actions neuropeptides elicit to support temperature-robust activity remain unknown. Here, we find that peptide neuromodulation restores rhythmic bursting in temperature-compromised central pattern generator (CPG) neurons by counteracting membrane shunt and increasing dendritic electrical spread. We show that acutely rising temperatures reduced spike generation and interrupted ongoing rhythmic motor activity in the crustacean gastric mill CPG. Neuronal release and extrinsic application of Cancer borealis tachykininrelated peptide Ia (CabTRP Ia), a substance-P-related peptide, restored rhythmic activity. Warming led to a significant decrease in membrane resistance and a shunting of the dendritic signals in the main gastric mill CPG neuron. Using a combination of fluorescent calcium imaging and electrophysiology, we observed that postsynaptic potentials and antidromic action potentials propagated less far within the dendritic neuropil as the system warmed. In the presence of CabTRP Ia, membrane shunt decreased and both postsynaptic potentials and antidromic action potentials propagated farther. At elevated temperatures, CabTRP Ia restored dendritic electrical spread or extended it beyond that at cold temperatures. Selective introduction of the CabTRP Ia conductance using a dynamic clamp demonstrated that the CabTRP Ia voltage-dependent conductance was sufficient to restore rhythmic bursting. Our findings demonstrate that a substance-P-related neuropeptide can boost dendritic electrical spread to maintain neuronal activity when perturbed and reveals key neurophysiological components of neuropeptide actions that support pattern generation in temperature-compromised conditions.

Neuromodulation Enables Temperature Robustness and Coupling Between Fast and Slow Oscillator Circuits

“…In previous studies ( Städele et al, 2015 ; DeMaegd and Stein, 2021 ), we have shown that extrinsic modulation enables the temperature robustness of a specific version of the gastric mill rhythm, elicited by the paired descending modulatory projection neuron MCN1. Specifically, the peptide co-transmitter of MCN1, CabTRP Ia, reduces shunting in LG to counterbalance an excessive increase in LG leak currents.…”

“…In a previous study, we showed that leak conductance of the core gastric mill CPG neuron LG increases with temperature ( Städele et al, 2015 ). If not counterbalanced by MCN1, this increase in leak conductance shunts synaptic signal propagation and stops LG spike activity and consequently the gastric mill rhythm ( DeMaegd and Stein, 2021 ). While in this previous study the gastric mill rhythm only involved one projection neuron, namely MCN1, it is likely that a similar increase in LG leak conductance occurs in all versions of the gastric mill rhythm when temperature is raised at the STG circuits.…”

“…MCN1 releases the substance P-related neuropeptide, CabTRP Ia ( Cancer borealis tachykinin-related peptide Ia), and our previous findings show that CabTRP Ia can counterbalance the temperature-induced increase in LG’s leak and sustain LG activity at elevated temperature when bath-applied or neuronally released. This temperature compensation is mediated through the neuromodulator-induced current I MI ( DeMaegd and Stein, 2021 ), which is activated by CabTRP Ia and several other neuropeptides, as well as some muscarinic agonists ( Swensen and Marder, 2000 ). Crustacean cardioactive peptide (CCAP), for example, is a hormone that induces I MI in LG ( DeLong et al, 2009 ) and can also confer temperature robustness to the gastric mill rhythm ( DeMaegd and Stein, 2021 ).…”

“…It is also clear that such extrinsic neuromodulatory input can sustain the gastric mill rhythm at elevated temperatures. We have demonstrated that increased neuropeptide release from descending modulatory projection neurons rescues the gastric mill rhythm from a crash at elevated temperature, and that projection neuron activity can increase with temperature ( Städele et al, 2015 ; DeMaegd and Stein, 2021 ). It has also been demonstrated that in intact animals, where temperature changes affect both, CPG circuits and their extrinsic modulatory inputs, the gastric mill rhythm is sustained at elevated temperatures.…”

The dynamic range of voltage-dependent gap junction signaling is maintained by Ih-induced membrane potential depolarization

“…The STG is subject to extensive modulation by neuromodulators that reach the STG either in the form of neurohormones [28], or by being released from sensory cells and the axon terminals of the projection neurons [29]. Their presence alters circuit output or robustness [7,[30][31][32][33]. This opens the fascinating possibility that the voltage dependence of the MCN1-LG ePSPs could be rapidly altered by modulation of I h in the MCN1 axon terminal or by activating other ionic conductances that alter the MCN1 terminal membrane potential.…”