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. 2022 Oct 12;42(41):7690–7706. doi: 10.1523/JNEUROSCI.0570-22.2022

Figure 8.

Figure 8.

Spike afterhyperpolarizations regulate persistent firing modes in hippocampal CA1 pyramidal cells. A, Activation of muscarinic receptors with CCh (2 μm) enables a persistent discharge following a step stimulus in a CA1 pyramidal cell (blue trace). B, The same CCh treatment increase failed to trigger persistent firing in a CA3 pyramidal cell. C, Summary plot of probabilities of triggering persistent firing in CCh in CA1 and CA3 hippocampal pyramidal cells and TeA L5 neocortical pyramidal cells. Probabilities of triggering persistence estimated from two different holding potentials (−65 and −70 mV) in each cell type. D, Persistent firing in CA1 pyramidal neurons exposed to CCh is blocked by terfenadine (10 μm; orange trace). E, Attenuating ERG conductance with terfenadine had little effect on the step response in a CA3 pyramidal cell. Inset, Enlargement of the initial phase of the afterhyperpolarization before and after terfenadine treatment. F, Summary plot of change in apparent input resistance of CA1 pyramidal cells during persistent activity using the same methodology as the experiment shown in Figure 2A. Input resistance was estimated in CCh (blue plot) and in response to similar depolarizing step stimuli in control conditions (black plot) and after persistent firing was abolished by terfenadine (orange plot). Magnitude of maximal change in input resistance plotted in inset: *p = 0.013, T = 4.227, df = 4; paired t test. G, Attenuating SK conductances with NS309 (2 μm) converted persistent firing into self-terminating discharges in CA1 pyramidal cells (blue traces). H, Applying microcontroller-based closed-loop feedback to selectively enhance spike afterhyperpolarizations terminated persistent firing in a CA1 pyramidal cell. Hyperpolarizing current transients commanded by the microcontroller shown in orange trace. As with the neocortical neuron experiment in Figure 6B, the closed-loop system only modulated the magnitude of the spike afterhyperpolarization during the persistent firing phase, not during the depolarizing step stimulus.