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Phasic firing in vasopressin cells: understanding its functional significance through computational models.

MacGregor DJ, Leng G - PLoS Comput. Biol. (2012)

Bottom Line: By comparison with the non-phasic population, the phasic population responds linearly to increases in tonic synaptic input.Non-phasic cells respond to transient elevations in synaptic input in a way that strongly depends on background activity levels, phasic cells in a way that is independent of background levels, and show a similar strong linearization of the response.These findings show large differences in information coding between the populations, and apparent functional advantages of asynchronous phasic firing.

View Article: PubMed Central - PubMed

Affiliation: Centre for Integrative Physiology, University of Edinburgh, Edinburgh, United Kingdom.

ABSTRACT
Vasopressin neurons, responding to input generated by osmotic pressure, use an intrinsic mechanism to shift from slow irregular firing to a distinct phasic pattern, consisting of long bursts and silences lasting tens of seconds. With increased input, bursts lengthen, eventually shifting to continuous firing. The phasic activity remains asynchronous across the cells and is not reflected in the population output signal. Here we have used a computational vasopressin neuron model to investigate the functional significance of the phasic firing pattern. We generated a concise model of the synaptic input driven spike firing mechanism that gives a close quantitative match to vasopressin neuron spike activity recorded in vivo, tested against endogenous activity and experimental interventions. The integrate-and-fire based model provides a simple physiological explanation of the phasic firing mechanism involving an activity-dependent slow depolarising afterpotential (DAP) generated by a calcium-inactivated potassium leak current. This is modulated by the slower, opposing, action of activity-dependent dendritic dynorphin release, which inactivates the DAP, the opposing effects generating successive periods of bursting and silence. Model cells are not spontaneously active, but fire when perturbed by random perturbations mimicking synaptic input. We constructed one population of such phasic neurons, and another population of similar cells but which lacked the ability to fire phasically. We then studied how these two populations differed in the way that they encoded changes in afferent inputs. By comparison with the non-phasic population, the phasic population responds linearly to increases in tonic synaptic input. Non-phasic cells respond to transient elevations in synaptic input in a way that strongly depends on background activity levels, phasic cells in a way that is independent of background levels, and show a similar strong linearization of the response. These findings show large differences in information coding between the populations, and apparent functional advantages of asynchronous phasic firing.

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The vasopressin spike firing model.Schematic illustrating the structure of the integrate-and-fire based single neuron spiking model. Input is a Poisson random timed mix of excitatory and inhibitory pulses, simulating PSPs. These are summed to generate a membrane potential which is also modulated by a set of spike triggered Ca2+ based potentials. The HAP, fast DAP and AHP are based on simple decaying exponentials, similar to a previous oxytocin cell model [19], [24]. The K+ leak current based slow DAP which generates bursting is based on the mechanism of the Hodgkin-Huxley type model of [16]. Spikes are generated when the membrane potential crosses a threshold value.
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pcbi-1002740-g001: The vasopressin spike firing model.Schematic illustrating the structure of the integrate-and-fire based single neuron spiking model. Input is a Poisson random timed mix of excitatory and inhibitory pulses, simulating PSPs. These are summed to generate a membrane potential which is also modulated by a set of spike triggered Ca2+ based potentials. The HAP, fast DAP and AHP are based on simple decaying exponentials, similar to a previous oxytocin cell model [19], [24]. The K+ leak current based slow DAP which generates bursting is based on the mechanism of the Hodgkin-Huxley type model of [16]. Spikes are generated when the membrane potential crosses a threshold value.

Mentions: We explored whether adding a second, slower, simple DAP could generate quantitatively realistic burst firing in the IGF model. A sustained plateau could be achieved if the DAP half life was >2 s, and combined with saturation to limit the DAP magnitude. Given the ability to sustain a plateau, an activity-dependent mechanism is required to terminate the bursts. Physiologically, this involves spike-dependent release of dynorphin which inhibits the DAP. Using a slow spike-dependent exponentially decaying variable to inhibit the DAP, combined with a hyperpolarised resting potential (−75 mV), we could produce bursts, but could not achieve sharp bistable switches in activity, and could not produce in vivo comparable silent periods, only periods of slower activity. The Roper model [15], [16] uses a different DAP mechanism to solve these problems; the burst plateau is generated by fully suppressing a hyperpolarising K+ leak current that is partially active at resting potential, and silences are periods where the K+ leak current is fully active, suppressing firing. This single mechanism can generate both activity dependent depolarisation and hyperpolarisation. Its model form, fitted to in vitro data, includes saturation and a simple relation between competing spike-triggered increases in [Ca2+]i and dynorphin, allowing dynorphin accumulation to eventually switch off a burst and generate a prolonged silence. This mechanism was simplified and integrated into the IGF model to produce the design illustrated in Figure 1.


Phasic firing in vasopressin cells: understanding its functional significance through computational models.

MacGregor DJ, Leng G - PLoS Comput. Biol. (2012)

The vasopressin spike firing model.Schematic illustrating the structure of the integrate-and-fire based single neuron spiking model. Input is a Poisson random timed mix of excitatory and inhibitory pulses, simulating PSPs. These are summed to generate a membrane potential which is also modulated by a set of spike triggered Ca2+ based potentials. The HAP, fast DAP and AHP are based on simple decaying exponentials, similar to a previous oxytocin cell model [19], [24]. The K+ leak current based slow DAP which generates bursting is based on the mechanism of the Hodgkin-Huxley type model of [16]. Spikes are generated when the membrane potential crosses a threshold value.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3475655&req=5

pcbi-1002740-g001: The vasopressin spike firing model.Schematic illustrating the structure of the integrate-and-fire based single neuron spiking model. Input is a Poisson random timed mix of excitatory and inhibitory pulses, simulating PSPs. These are summed to generate a membrane potential which is also modulated by a set of spike triggered Ca2+ based potentials. The HAP, fast DAP and AHP are based on simple decaying exponentials, similar to a previous oxytocin cell model [19], [24]. The K+ leak current based slow DAP which generates bursting is based on the mechanism of the Hodgkin-Huxley type model of [16]. Spikes are generated when the membrane potential crosses a threshold value.
Mentions: We explored whether adding a second, slower, simple DAP could generate quantitatively realistic burst firing in the IGF model. A sustained plateau could be achieved if the DAP half life was >2 s, and combined with saturation to limit the DAP magnitude. Given the ability to sustain a plateau, an activity-dependent mechanism is required to terminate the bursts. Physiologically, this involves spike-dependent release of dynorphin which inhibits the DAP. Using a slow spike-dependent exponentially decaying variable to inhibit the DAP, combined with a hyperpolarised resting potential (−75 mV), we could produce bursts, but could not achieve sharp bistable switches in activity, and could not produce in vivo comparable silent periods, only periods of slower activity. The Roper model [15], [16] uses a different DAP mechanism to solve these problems; the burst plateau is generated by fully suppressing a hyperpolarising K+ leak current that is partially active at resting potential, and silences are periods where the K+ leak current is fully active, suppressing firing. This single mechanism can generate both activity dependent depolarisation and hyperpolarisation. Its model form, fitted to in vitro data, includes saturation and a simple relation between competing spike-triggered increases in [Ca2+]i and dynorphin, allowing dynorphin accumulation to eventually switch off a burst and generate a prolonged silence. This mechanism was simplified and integrated into the IGF model to produce the design illustrated in Figure 1.

Bottom Line: By comparison with the non-phasic population, the phasic population responds linearly to increases in tonic synaptic input.Non-phasic cells respond to transient elevations in synaptic input in a way that strongly depends on background activity levels, phasic cells in a way that is independent of background levels, and show a similar strong linearization of the response.These findings show large differences in information coding between the populations, and apparent functional advantages of asynchronous phasic firing.

View Article: PubMed Central - PubMed

Affiliation: Centre for Integrative Physiology, University of Edinburgh, Edinburgh, United Kingdom.

ABSTRACT
Vasopressin neurons, responding to input generated by osmotic pressure, use an intrinsic mechanism to shift from slow irregular firing to a distinct phasic pattern, consisting of long bursts and silences lasting tens of seconds. With increased input, bursts lengthen, eventually shifting to continuous firing. The phasic activity remains asynchronous across the cells and is not reflected in the population output signal. Here we have used a computational vasopressin neuron model to investigate the functional significance of the phasic firing pattern. We generated a concise model of the synaptic input driven spike firing mechanism that gives a close quantitative match to vasopressin neuron spike activity recorded in vivo, tested against endogenous activity and experimental interventions. The integrate-and-fire based model provides a simple physiological explanation of the phasic firing mechanism involving an activity-dependent slow depolarising afterpotential (DAP) generated by a calcium-inactivated potassium leak current. This is modulated by the slower, opposing, action of activity-dependent dendritic dynorphin release, which inactivates the DAP, the opposing effects generating successive periods of bursting and silence. Model cells are not spontaneously active, but fire when perturbed by random perturbations mimicking synaptic input. We constructed one population of such phasic neurons, and another population of similar cells but which lacked the ability to fire phasically. We then studied how these two populations differed in the way that they encoded changes in afferent inputs. By comparison with the non-phasic population, the phasic population responds linearly to increases in tonic synaptic input. Non-phasic cells respond to transient elevations in synaptic input in a way that strongly depends on background activity levels, phasic cells in a way that is independent of background levels, and show a similar strong linearization of the response. These findings show large differences in information coding between the populations, and apparent functional advantages of asynchronous phasic firing.

Show MeSH
Related in: MedlinePlus