Hippocampal CA1 pyramidal neurons exhibit type 1 phase-response curves and type 1 excitability

Abstract

Phase-resetting properties of neurons determine their functionality as integrators (type 1) vs. resonators (type 2), as well as their synchronization tendencies. We introduce a novel, bias-correction method to estimate the infinitesimal phase-resetting curve (iPRC) and confirm type 1 excitability in hippocampal pyramidal CA1 neurons in vitro by two independent methods. First, PRCs evoked using depolarizing pulses consisted only of advances, consistent with type 1. Second, the frequency/current (f/I) plots showed no minimum frequency, again consistent with type 1. Type 1 excitability was also confirmed by the absence of a resonant peak in the interspike interval histograms derived from the f/I data. The PRC bias correction assumed that the distribution of noisy phase resetting is truncated, because an input cannot advance a spike to a point in time before the input (the causal limit) and successfully removed the statistical bias for delays in the null PRC in response to zero-magnitude input by computing the phase resetting as the mean of the untruncated distribution. The PRC for depolarization peaked at late phases and decreased to zero by the end of the cycle, whereas delays observed in response to hyperpolarization increased monotonically. The bias correction did not affect this difference in shape, which was due instead to the causal limit obscuring the iPRC for depolarization but not hyperpolarization. Our results suggest that weak periodic hyperpolarizing drive can theoretically entrain CA1 pyramidal neurons at any phase but that strong excitation will preferentially phase-lock them with zero time lag.

Phase-resetting as a tool of information transmission

“…Phase-resetting characteristics can be measured for a single oscillating neuron [11,12] or for network oscillators [13,14]. Figure 1 defines the phase of an oscillator and shows how it can be reset, using a simple network oscillator model [15] that consists of the average firing rates of two neural populations, one excitatory (E) and one inhibitory (I).…”

“…The biphasic response is due to the unconventional protocol; when CA1 neurons are biased in a pacemaker regime they exhibit a monophasic PRC [11]. …”

Effect of Heterogeneity and Noise on Cross Frequency Phase-Phase and Phase-Amplitude Coupling

“…We used both depolarizing pulses (Figure 3A1) and hyperpolarizing pulses (Figure 3A2) as described in the Experimental Methods. CA1 pyramidal neurons have a “N” shaped I–V curve (Yamada-Hanff and Bean 2013) that allows them to fire tonically in response to the application of depolarizing current (Wang et al 2013) or a net increase in depolarizing current produced by the neuromodulatory effects of ACh (Yamada-Hanff and Bean 2013). Here we show the existence of 1:1 and 1:2 locking windows in response to periodic trains of depolarizing or inhibitory pulses.…”

“…After letting the firing frequency stabilize (> 20 seconds), brief (3 ms) hyperpolarizing or depolarizing current steps (150–250 pA) were injected at various frequencies to mimic a synaptic input (Wang et al 2013). …”

Sensitivity Analysis of Oscillator Models in the Space of Phase-Response Curves: Oscillators As Open Systems

“…Limitations of the infinitesimal approach have been well identified since the early days of phaseresetting studies [1] and strongly depend on the application context. For instance, infinitesimal phase-response curves have proven very useful in the study of circadian rhythms [24] but come with severe limitations in the context of neurodynamics, as recently studied in [25]- [27].…”