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A unifying computational framework for stability and flexibility of arousal.

Kosse C, Burdakov D - Front Syst Neurosci (2014)

Bottom Line: Experiments are proposed for testing such predictions, based on computational simulations showing that comparators, regulators, and generators have distinct temporal signatures of activity.An integral feedback view also suggests functional roles for specific molecular aspects, such as differing life-spans of orexin peptides.The proposed framework offers a unifying logic for molecular, cellular, and network details of arousal systems, and provides insight into behavioral state transitions, complex behavior, and bases for disease.

View Article: PubMed Central - PubMed

Affiliation: Neurophysiology, MRC National Institute for Medical Research London, UK.

ABSTRACT
Arousal and consciousness flexibly adjust to salient cues, but remain stable despite noise and disturbance. Diverse, highly interconnected neural networks govern the underlying transitions of behavioral state; these networks are robust but very complex. Frameworks from systems engineering provide powerful tools for understanding functional logic behind component complexity. From a general systems viewpoint, a minimum of three communicating control modules may enable flexibility and stability to coexist. Comparators would subtract current arousal from desired arousal, producing an error signal. Regulators would compute control signals from this error. Generators would convert control signals into arousal, which is fed back to comparators, to make the system noise-proof through self-correction. Can specific neurons correspond to these control elements? To explore this, here we consider the brain-wide orexin/hypocretin network, which is experimentally established to be vital for flexible and stable arousal. We discuss whether orexin neurons may act as comparators, and their target neurons as regulators and generators. Experiments are proposed for testing such predictions, based on computational simulations showing that comparators, regulators, and generators have distinct temporal signatures of activity. If some regulators integrate orexin-communicated errors, robust arousal control may be achieved via integral feedback (a basic engineering strategy for tracking a set-point despite noise). An integral feedback view also suggests functional roles for specific molecular aspects, such as differing life-spans of orexin peptides. The proposed framework offers a unifying logic for molecular, cellular, and network details of arousal systems, and provides insight into behavioral state transitions, complex behavior, and bases for disease.

No MeSH data available.


Related in: MedlinePlus

Integrators and their hypothetical neural correlates. (A) Theoretical input-output dynamics of neurons that act as multipliers (top left graph), or integrators (top right graph) with different integration windows (bottom graph). W here is defined as the duration of integration window, i.e., given . Input is shown in magenta, and output in green. (B) Experimental input-output relations of neurons in brain orexin circuits. Top row, firing outputs of orexin/hypocretin neurons (OHNs ) in response to bath application of 1 µM (left) and 200 nM (right) orexin/hypocretin peptides (from Li and van den Pol, 2006, reproduced with permission from The Society for Neuroscience). Bottom row, firing outputs of histamine neurons (HAN) in response to optogenetic stimulation of OHNs at 20 Hz (blue bar). Responses due to orexin transmission are in red (data from Schöne et al., 2014).
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Figure 2: Integrators and their hypothetical neural correlates. (A) Theoretical input-output dynamics of neurons that act as multipliers (top left graph), or integrators (top right graph) with different integration windows (bottom graph). W here is defined as the duration of integration window, i.e., given . Input is shown in magenta, and output in green. (B) Experimental input-output relations of neurons in brain orexin circuits. Top row, firing outputs of orexin/hypocretin neurons (OHNs ) in response to bath application of 1 µM (left) and 200 nM (right) orexin/hypocretin peptides (from Li and van den Pol, 2006, reproduced with permission from The Society for Neuroscience). Bottom row, firing outputs of histamine neurons (HAN) in response to optogenetic stimulation of OHNs at 20 Hz (blue bar). Responses due to orexin transmission are in red (data from Schöne et al., 2014).

Mentions: From a general systems point of view, it can be argued that pressure to develop good policies for stable-yet-flexible function is not unique to biological evolution (Csete and Doyle, 2002, 2004). For example, under consumer pressure, in recent decades diverse robotic devices (thermostats, car cruise-controllers) also evolved remarkably effective strategies to make their controlled variables (temperature, speed, etc.) follow set-points despite disturbance. For example, a car cruise-controller can defend set-point speed despite unpredictable variations in slope, wind, or component function, by employing a feedback mechanism (Figure 1A). It has been proposed that, faced with similar general problems (i.e., tracking a set-point despite unpredictable noise), biological and engineering systems undergo a convergent evolution and arrive at similar solutions, such as self-correction via feedback (Csete and Doyle, 2002, 2004). Reverse engineering of biology may therefore benefit from broader frameworks in engineering (Csete and Doyle, 2002; Franklin and Wolpert, 2011).


A unifying computational framework for stability and flexibility of arousal.

Kosse C, Burdakov D - Front Syst Neurosci (2014)

Integrators and their hypothetical neural correlates. (A) Theoretical input-output dynamics of neurons that act as multipliers (top left graph), or integrators (top right graph) with different integration windows (bottom graph). W here is defined as the duration of integration window, i.e., given . Input is shown in magenta, and output in green. (B) Experimental input-output relations of neurons in brain orexin circuits. Top row, firing outputs of orexin/hypocretin neurons (OHNs ) in response to bath application of 1 µM (left) and 200 nM (right) orexin/hypocretin peptides (from Li and van den Pol, 2006, reproduced with permission from The Society for Neuroscience). Bottom row, firing outputs of histamine neurons (HAN) in response to optogenetic stimulation of OHNs at 20 Hz (blue bar). Responses due to orexin transmission are in red (data from Schöne et al., 2014).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4202806&req=5

Figure 2: Integrators and their hypothetical neural correlates. (A) Theoretical input-output dynamics of neurons that act as multipliers (top left graph), or integrators (top right graph) with different integration windows (bottom graph). W here is defined as the duration of integration window, i.e., given . Input is shown in magenta, and output in green. (B) Experimental input-output relations of neurons in brain orexin circuits. Top row, firing outputs of orexin/hypocretin neurons (OHNs ) in response to bath application of 1 µM (left) and 200 nM (right) orexin/hypocretin peptides (from Li and van den Pol, 2006, reproduced with permission from The Society for Neuroscience). Bottom row, firing outputs of histamine neurons (HAN) in response to optogenetic stimulation of OHNs at 20 Hz (blue bar). Responses due to orexin transmission are in red (data from Schöne et al., 2014).
Mentions: From a general systems point of view, it can be argued that pressure to develop good policies for stable-yet-flexible function is not unique to biological evolution (Csete and Doyle, 2002, 2004). For example, under consumer pressure, in recent decades diverse robotic devices (thermostats, car cruise-controllers) also evolved remarkably effective strategies to make their controlled variables (temperature, speed, etc.) follow set-points despite disturbance. For example, a car cruise-controller can defend set-point speed despite unpredictable variations in slope, wind, or component function, by employing a feedback mechanism (Figure 1A). It has been proposed that, faced with similar general problems (i.e., tracking a set-point despite unpredictable noise), biological and engineering systems undergo a convergent evolution and arrive at similar solutions, such as self-correction via feedback (Csete and Doyle, 2002, 2004). Reverse engineering of biology may therefore benefit from broader frameworks in engineering (Csete and Doyle, 2002; Franklin and Wolpert, 2011).

Bottom Line: Experiments are proposed for testing such predictions, based on computational simulations showing that comparators, regulators, and generators have distinct temporal signatures of activity.An integral feedback view also suggests functional roles for specific molecular aspects, such as differing life-spans of orexin peptides.The proposed framework offers a unifying logic for molecular, cellular, and network details of arousal systems, and provides insight into behavioral state transitions, complex behavior, and bases for disease.

View Article: PubMed Central - PubMed

Affiliation: Neurophysiology, MRC National Institute for Medical Research London, UK.

ABSTRACT
Arousal and consciousness flexibly adjust to salient cues, but remain stable despite noise and disturbance. Diverse, highly interconnected neural networks govern the underlying transitions of behavioral state; these networks are robust but very complex. Frameworks from systems engineering provide powerful tools for understanding functional logic behind component complexity. From a general systems viewpoint, a minimum of three communicating control modules may enable flexibility and stability to coexist. Comparators would subtract current arousal from desired arousal, producing an error signal. Regulators would compute control signals from this error. Generators would convert control signals into arousal, which is fed back to comparators, to make the system noise-proof through self-correction. Can specific neurons correspond to these control elements? To explore this, here we consider the brain-wide orexin/hypocretin network, which is experimentally established to be vital for flexible and stable arousal. We discuss whether orexin neurons may act as comparators, and their target neurons as regulators and generators. Experiments are proposed for testing such predictions, based on computational simulations showing that comparators, regulators, and generators have distinct temporal signatures of activity. If some regulators integrate orexin-communicated errors, robust arousal control may be achieved via integral feedback (a basic engineering strategy for tracking a set-point despite noise). An integral feedback view also suggests functional roles for specific molecular aspects, such as differing life-spans of orexin peptides. The proposed framework offers a unifying logic for molecular, cellular, and network details of arousal systems, and provides insight into behavioral state transitions, complex behavior, and bases for disease.

No MeSH data available.


Related in: MedlinePlus