A computational model for how the fast afterhyperpolarization paradoxically increases gain in regularly firing neurons

作者：Jaffe David B; Brenner Robert

来源：Journal of Neurophysiology, 2018, 119(4): 1506-1520.

DOI：10.1152/jn.00385.2017

<jats:p> The gain of a neuron, the number and frequency of action potentials triggered in response to a given amount of depolarizing injection, is an important behavior underlying a neuron’s function. Variations in action potential waveform can influence neuronal discharges by the differential activation of voltage- and ion-gated channels long after the end of a spike. One component of the action potential waveform, the afterhyperpolarization (AHP), is generally considered an inhibitory mechanism for limiting firing rates. In dentate gyrus granule cells (DGCs) expressing fast-gated BK channels, large fast AHPs (fAHP) are paradoxically associated with increased gain. In this article, we describe a mechanism for this behavior using a computational model. Hyperpolarization provided by the fAHP enhances activation of a dendritic inward current (a T-type Ca<jats:sup>2+</jats:sup> channel is suggested) that, in turn, boosts rebound depolarization at the soma. The model suggests that the fAHP may both reduce Ca<jats:sup>2+</jats:sup> channel inactivation and, counterintuitively, enhance its activation. The magnitude of the rebound depolarization, in turn, determines the activation of a subsequent, slower inward current (a persistent Na<jats:sup>+</jats:sup> current is suggested) limiting the interspike interval. Simulations also show that the effect of AHP on gain is also effective for physiologically relevant stimulation; varying AHP amplitude affects interspike interval across a range of “noisy” stimulus frequency and amplitudes. The mechanism proposed suggests that small fAHPs in DGCs may contribute to their limited excitability. </jats:p><jats:p> NEW &amp; NOTEWORTHY The afterhyperpolarization (AHP) is canonically viewed as a major factor underlying the refractory period, serving to limit neuronal firing rate. We recently reported that enhancing the amplitude of the fast AHP (fAHP) in a relatively slowly firing neuron (vs. fast spiking neurons) expressing fast-gated BK channels augments neuronal excitability. In this computational study, we present a novel, quantitative hypothesis for how varying the amplitude of the fAHP can, paradoxically, influence a subsequent spike tens of milliseconds later. </jats:p>

• 出版日期2018-4
• 单位University of Texas; The University of Texas; University of Texas Health Science Center at San Antonio