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Neuromodulation to the Rescue: Compensation of Temperature-Induced Breakdown of Rhythmic Motor Patterns via Extrinsic Neuromodulatory Input.

Städele C, Heigele S, Stein W - PLoS Biol. (2015)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Institute of Neurobiology, Ulm University, Ulm, Germany; School of Biological Sciences, Illinois State University, Normal, Illinois, United States of America.

ABSTRACT
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.

No MeSH data available.


Related in: MedlinePlus

Changes in leak conductance are sufficient to terminate and rescue the rhythm.(A) Top: Intracellular recording of LG during tonic MCN1 stimulation with 7 Hz at 10°C. Rhythmic activity ceased when artificial leak was added with dynamic clamp (10°C + Δleak). Bottom: Corresponding dynamic clamp current that was injected into LG. (B) Top: Intracellular recording of LG during tonic MCN1 stimulation with 7 Hz at 13°C. Rhythmic activity was recovered when artificial leak was subtracted (13°C − Δleak). Bottom: Corresponding dynamic clamp current that was injected into LG. Traces in B and C are from the same preparation. (C) Effect of artificial leak addition (10°C + Δleak) and subtraction (13°C − Δleak) on LG spike activity for all tested preparations (1 to 4). Each vertical line represents an AP in LG over 100 s of continuous MCN1 stimulation. Grey traces (4) correspond to recordings shown in A and B.
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pbio.1002265.g004: Changes in leak conductance are sufficient to terminate and rescue the rhythm.(A) Top: Intracellular recording of LG during tonic MCN1 stimulation with 7 Hz at 10°C. Rhythmic activity ceased when artificial leak was added with dynamic clamp (10°C + Δleak). Bottom: Corresponding dynamic clamp current that was injected into LG. (B) Top: Intracellular recording of LG during tonic MCN1 stimulation with 7 Hz at 13°C. Rhythmic activity was recovered when artificial leak was subtracted (13°C − Δleak). Bottom: Corresponding dynamic clamp current that was injected into LG. Traces in B and C are from the same preparation. (C) Effect of artificial leak addition (10°C + Δleak) and subtraction (13°C − Δleak) on LG spike activity for all tested preparations (1 to 4). Each vertical line represents an AP in LG over 100 s of continuous MCN1 stimulation. Grey traces (4) correspond to recordings shown in A and B.

Mentions: We next tested whether an increase in leak conductance is sufficient to explain the termination of the gastric mill rhythm by using the dynamic clamp technique [28]. We either added an artificial leak conductance at 10°C or subtracted leak conductance at 13°C. First, we measured LG input resistance and resting potential at 10°C and 13°C and used the difference to calculate the leak conductance increase (= Δleak, see Materials and Methods). We then elicited a gastric mill rhythm at 10°C, and after several gastric mill cycles, we turned the dynamic clamp on and injected the appropriate amount of additional leak (+Δleak). Immediately after the onset of the artificial leak conductance, LG bursting ceased (Fig 4A). Thus, an increase in leak conductance as caused by a temperature increase of 3°C was sufficient to terminate the gastric mill rhythm.


Neuromodulation to the Rescue: Compensation of Temperature-Induced Breakdown of Rhythmic Motor Patterns via Extrinsic Neuromodulatory Input.

Städele C, Heigele S, Stein W - PLoS Biol. (2015)

Changes in leak conductance are sufficient to terminate and rescue the rhythm.(A) Top: Intracellular recording of LG during tonic MCN1 stimulation with 7 Hz at 10°C. Rhythmic activity ceased when artificial leak was added with dynamic clamp (10°C + Δleak). Bottom: Corresponding dynamic clamp current that was injected into LG. (B) Top: Intracellular recording of LG during tonic MCN1 stimulation with 7 Hz at 13°C. Rhythmic activity was recovered when artificial leak was subtracted (13°C − Δleak). Bottom: Corresponding dynamic clamp current that was injected into LG. Traces in B and C are from the same preparation. (C) Effect of artificial leak addition (10°C + Δleak) and subtraction (13°C − Δleak) on LG spike activity for all tested preparations (1 to 4). Each vertical line represents an AP in LG over 100 s of continuous MCN1 stimulation. Grey traces (4) correspond to recordings shown in A and B.
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Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4587842&req=5

pbio.1002265.g004: Changes in leak conductance are sufficient to terminate and rescue the rhythm.(A) Top: Intracellular recording of LG during tonic MCN1 stimulation with 7 Hz at 10°C. Rhythmic activity ceased when artificial leak was added with dynamic clamp (10°C + Δleak). Bottom: Corresponding dynamic clamp current that was injected into LG. (B) Top: Intracellular recording of LG during tonic MCN1 stimulation with 7 Hz at 13°C. Rhythmic activity was recovered when artificial leak was subtracted (13°C − Δleak). Bottom: Corresponding dynamic clamp current that was injected into LG. Traces in B and C are from the same preparation. (C) Effect of artificial leak addition (10°C + Δleak) and subtraction (13°C − Δleak) on LG spike activity for all tested preparations (1 to 4). Each vertical line represents an AP in LG over 100 s of continuous MCN1 stimulation. Grey traces (4) correspond to recordings shown in A and B.
Mentions: We next tested whether an increase in leak conductance is sufficient to explain the termination of the gastric mill rhythm by using the dynamic clamp technique [28]. We either added an artificial leak conductance at 10°C or subtracted leak conductance at 13°C. First, we measured LG input resistance and resting potential at 10°C and 13°C and used the difference to calculate the leak conductance increase (= Δleak, see Materials and Methods). We then elicited a gastric mill rhythm at 10°C, and after several gastric mill cycles, we turned the dynamic clamp on and injected the appropriate amount of additional leak (+Δleak). Immediately after the onset of the artificial leak conductance, LG bursting ceased (Fig 4A). Thus, an increase in leak conductance as caused by a temperature increase of 3°C was sufficient to terminate the gastric mill rhythm.

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Institute of Neurobiology, Ulm University, Ulm, Germany; School of Biological Sciences, Illinois State University, Normal, Illinois, United States of America.

ABSTRACT
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.

No MeSH data available.


Related in: MedlinePlus