Abstract
Neurons from many brain regions display intrinsic subthreshold theta-resonance, responding preferentially to theta-frequency oscillatory stimuli. Resonance may contribute to selective communication among neurons and to orchestrate brain rhythms. CA1 pyramidal neurons receive theta activity, generating place fields. In these neurons the expression of perithreshold frequency preference is controversial, particularly in the spiking regime, with evidence favoring either non-resonant (integrator-like) or resonant behavior. Perithreshold dynamics depends on the persistent Na+ current INaP developing above −70 mV and the muscarine-sensitive K+ current IM activating above −60 mV. We conducted current and voltage clamp experiments in slices to investigate perithreshold excitability of CA1 neurons under oscillatory stimulation. Around 20% of neurons displayed perithreshold resonance that is expressed in spiking. The remaining neurons (~80%) acted as low-pass filters lacking frequency preference. Paired voltage clamp measurement of INaP and IM showed that perithreshold activation of IM is in general low while INaP is high enough to depolarize neurons toward threshold before resonance expression, explaining the most abundant non-resonant perithreshold behavior. Partial blockade of INaP by pharmacological tools or dynamic clamp changed non-resonant to resonant behavior. Furthermore, shifting IM activation toward hyperpolarized potentials by dynamic clamp also transformed non-resonant neurons into resonant ones. We propose that the relative levels of INaP and IM control perithreshold behavior of CA1 neurons constituting a gating mechanism for theta resonance in the spiking regime. Both currents are regulated by intracellular signaling and neuromodulators which may allow dynamic switching of perithreshold behavior between resonant and non-resonant.
Highlights
Many cognitive and behavioral processes like memory and navigation depend on hippocampal function and rely on network oscillatory activity at frequencies around 4–10 Hz, known as the theta range (O’Keefe and Recce, 1993; Buzsáki, 2002, 2005; Lisman, 2005)
We set the ZAP amplitude to produce a peak-to-peak voltage oscillation of ∼5–8 mV, while neurons were maintained at different subthreshold potentials by the injection of a stable holding current; for simplicity, we will refer to this potential as “holding potential.”
We report that CA1 pyramidal neurons present two different types of behaviors when stimulated with an oscillatory current of variable frequency that spans the theta range (0–20 Hz)
Summary
Many cognitive and behavioral processes like memory and navigation depend on hippocampal function and rely on network oscillatory activity at frequencies around 4–10 Hz, known as the theta range (O’Keefe and Recce, 1993; Buzsáki, 2002, 2005; Lisman, 2005). Shaping Perithreshold Theta-Resonance in Neurons at theta frequency, displaying an increased subthreshold voltage response for rhythmic stimulation in the theta range, acting as resonators (Hu et al, 2002) This selective voltage response or frequency preference is the result of active and passive mechanisms. Specific slowly-activating membrane currents produce an active attenuation of low-frequency voltage responses, while the passive properties of the cellular membrane filter out high-frequency oscillations (Hutcheon and Yarom, 2000). This generates a band-pass filtering effect that tunes the voltage response of resonant neurons around a specific frequency of inputs (Izhikevich, 2002). Resonance strength is quantified by the Q-value corresponding to the ratio between ZMax and the impedance at 0.5 Hz (Hutcheon et al, 1996)
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