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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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Related in: MedlinePlus

Model cell behaviour with increasing synaptic input.When osmotic pressure is increased in vivo we see a shift to phasic firing followed by increases in intraburst firing rate and burst duration, eventually shifting to continuous firing [3]. Here, we reproduce this in the model (using parameters fitted to cell v2) by increasing synaptic input. Intraburst firing rate increases fairly linearly, whereas the increase in burst duration is much more non-linear. Silence duration shows a fairly linear decline after phasic firing is established.
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pcbi-1002740-g006: Model cell behaviour with increasing synaptic input.When osmotic pressure is increased in vivo we see a shift to phasic firing followed by increases in intraburst firing rate and burst duration, eventually shifting to continuous firing [3]. Here, we reproduce this in the model (using parameters fitted to cell v2) by increasing synaptic input. Intraburst firing rate increases fairly linearly, whereas the increase in burst duration is much more non-linear. Silence duration shows a fairly linear decline after phasic firing is established.

Mentions: In vivo, when osmotic input is increased, an increased proportion of vasopressin neurons fire phasically, shifting from slow irregular firing. Phasic neurons also show longer bursts, shorter silences, and higher intra-burst firing rates [3], eventually shifting to continuous firing. We tested this in the model by increasing the synaptic input rate. Similarly, model cells progress from slow sparse firing to short irregular bursts and then full phasic firing with bursts increasing in duration and firing rate and shortening silent periods, until they eventually shift to continuous firing (Figure 6). The increase in intraburst firing rate is more linear than the increase in burst duration due to the additional opposing effect of the AHP on firing rate.


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

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

Model cell behaviour with increasing synaptic input.When osmotic pressure is increased in vivo we see a shift to phasic firing followed by increases in intraburst firing rate and burst duration, eventually shifting to continuous firing [3]. Here, we reproduce this in the model (using parameters fitted to cell v2) by increasing synaptic input. Intraburst firing rate increases fairly linearly, whereas the increase in burst duration is much more non-linear. Silence duration shows a fairly linear decline after phasic firing is established.
© Copyright Policy
Related In: Results  -  Collection

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

pcbi-1002740-g006: Model cell behaviour with increasing synaptic input.When osmotic pressure is increased in vivo we see a shift to phasic firing followed by increases in intraburst firing rate and burst duration, eventually shifting to continuous firing [3]. Here, we reproduce this in the model (using parameters fitted to cell v2) by increasing synaptic input. Intraburst firing rate increases fairly linearly, whereas the increase in burst duration is much more non-linear. Silence duration shows a fairly linear decline after phasic firing is established.
Mentions: In vivo, when osmotic input is increased, an increased proportion of vasopressin neurons fire phasically, shifting from slow irregular firing. Phasic neurons also show longer bursts, shorter silences, and higher intra-burst firing rates [3], eventually shifting to continuous firing. We tested this in the model by increasing the synaptic input rate. Similarly, model cells progress from slow sparse firing to short irregular bursts and then full phasic firing with bursts increasing in duration and firing rate and shortening silent periods, until they eventually shift to continuous firing (Figure 6). The increase in intraburst firing rate is more linear than the increase in burst duration due to the additional opposing effect of the AHP on firing rate.

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