Stable rhythmic neural activity depends on the well-coordinated interplay of synaptic and cell-intrinsic conductances. Since all biophysical processes are temperature dependent, this interplay is challenged during temperature fluctuations. How the nervous system remains functional during temperature perturbations remains mostly unknown. We present a hitherto unknown mechanism of how temperature-induced changes in neural networks are compensated by changing their neuromodulatory state: activation of neuromodulatory pathways establishes a dynamic coregulation of synaptic and intrinsic conductances with opposing effects on neuronal activity when temperature changes, hence rescuing neuronal activity. Using the well-studied gastric mill pattern generator of the crab, we show that modest temperature increase can abolish rhythmic activity in isolated neural circuits due to increased leak currents in rhythm-generating neurons. Dynamic clamp-mediated addition of leak currents was sufficient to stop neuronal oscillations at low temperatures, and subtraction of additional leak currents at elevated temperatures was sufficient to rescue the rhythm. Despite the apparent sensitivity of the isolated nervous system to temperature fluctuations, the rhythm could be stabilized by activating extrinsic neuromodulatory inputs from descending projection neurons, a strategy that we indeed found to be implemented in intact animals. In the isolated nervous system, temperature compensation was achieved by stronger extrinsic neuromodulatory input from projection neurons or by augmenting projection neuron influence via bath application of the peptide cotransmitter Cancer borealis tachykinin-related peptide Ia (CabTRP Ia). CabTRP Ia activates the modulator-induced current IMI (a nonlinear voltage-gated inward current) that effectively acted as a negative leak current and counterbalanced the temperature-induced leak to rescue neuronal oscillations. Computational modelling revealed the ability of IMI to reduce detrimental leak-current influences on neuronal networks over a broad conductance range and indicated that leak and IMI are closely coregulated in the biological system to enable stable motor patterns. In conclusion, these results show that temperature compensation does not need to be implemented within the network itself but can be conditionally provided by extrinsic neuromodulatory input that counterbalances temperature-induced modifications of circuit-intrinsic properties.

Highlights d LC12 and LC15 are ON-OFF visual feature detectors d LC15 responds to moving bars, whereas LC12 responds to objects of any size d Object responses from both LCs are suppressed when the background is moving d Octopamine restores object responses in LC12 and LC15 against a moving background Authors

Graphical Abstract Highlights d LC11 neurons are suppressed by motion and flicker in the local surround d LC11 expresses a GABA receptor required for normal object detection d T2/T3 respond to ON and OFF components of object motion and flicker d T3 neurons excite LC11 and are required for normal LC11 function SUMMARYThe direction-selective T4/T5 cells innervate opticflow processing projection neurons in the lobula plate of the fly that mediate the visual control of locomotion. In the lobula, visual projection neurons coordinate complex behavioral responses to visual features, however, the input circuitry and computations that bestow their feature-detecting properties are less clear. Here, we study a highly specialized small object motion detector, LC11, and demonstrate that its responses are suppressed by local background motion. We show that LC11 expresses GABA-A receptors that serve to sculpt responses to small objects but are not responsible for the rejection of background motion. Instead, LC11 is innervated by columnar T2 and T3 neurons that are themselves highly sensitive to small static or moving objects, insensitive to wide-field motion and, unlike T4/T5, respond to both ON and OFF luminance steps.

Essential to understanding the process of neuronal signal integration is the knowledge of where within a neuron action potentials (APs) are generated. Recent studies support the idea that the precise location where APs are initiated and the properties of spike initiation zones define the cell's information processing capabilities. Notably, the location of spike initiation can be modified homeostatically within neurons to adjust neuronal activity. Here we show that this potential mechanism for neuronal plasticity can also be exploited in a rapid and dynamic fashion. We tested whether dislocation of the spike initiation zone affects signal integration by studying ectopic spike initiation in the anterior gastric receptor neuron (AGR) of the stomatogastric nervous system of Cancer borealis. Like many other vertebrate and invertebrate neurons, AGR can generate ectopic APs in regions distinct from the axon initial segment. Using voltagesensitive dyes and electrophysiology, we determined that AGR's ectopic spike activity was consistently initiated in the neuropil region of the stomatogastric ganglion motor circuits. At least one neurite branched off the AGR axon in this area; and indeed, we found that AGR's ectopic spike activity was influenced by local motor neurons. This sensorimotor interaction was state-dependent in that focal axon modulation with the biogenic amine octopamine, abolished signal integration at the primary spike initiation zone by dislocating spike initiation to a distant region of the axon. We demonstrate that the site of ectopic spike initiation is important for signal integration and that axonal neuromodulation allows for a dynamic adjustment of signal integration.