Subthreshold membrane resonance in neocortical neurons.
1. Using whole cell recording techniques, we studied subthreshold and suprathreshold voltage responses to oscillatory current inputs in neurons from the sensorimotor cortex of juvenile rats. 2. Based on firing patterns, neurons were classified as regular spiking (RS), intrinsic bursting (IB), and fast spiking (FS). The subthreshold voltage-current relationships of RS and IB neurons were rectifying whereas FS neurons were almost ohmic near rest. 3. Frequency response curves (FRCs) for neurons were determined by analyzing the frequency content of inputs and outputs. The FRCs of most neurons were voltage dependent at frequencies below, but not above, 20 Hz. Approximately 60% of RS and IB neurons had a membrane resonance at their resting potential. Resonant frequencies were between 0.7 and 2.5 Hz (24-26 degrees C) near -70 mV and usually increased with hyperpolarization and decreased with depolarization. The remaining RS and IB neurons and all FS neurons were nonresonant. 4. Resonant neurons near rest had a selective coupling between oscillatory inputs and firing. These neurons selectively fired action potentials when the frequency of the swept-sine-wave (ZAP) current input was near the resonant frequency. However, when these neurons were depolarized to -60 mV, spike firing was associated with many input frequencies rather than selectively near the resonant frequency. 5. We examined three subthreshold currents that could cause low-frequency resonance: IH, a slow, hyperpolarization-activated cation current that was blocked by external Cs+ but not Ba2+; IIR, an instantaneously activating, inwardly rectifying K+ current that was blocked by both Cs+ and Ba2+; and INaP, an quickly activating, inwardly rectifying persistent Na+ current that was blocked by tetrodotoxin (TTX). Voltage-clamp experiments defined the relative steady state activation ranges of these currents. IIR (activates below -80 mV) and INaP (activates above -65 mV) are unlikely to interact with each other because their activation ranges never overlap. However, both currents may interact with IH, which activated variably at potentials between -50 and -90 mV in different neurons. 6. We found that IH produces subthreshold response. Consistent with this, subthreshold resonance was blocked by external Cs+ but not Ba2+ or TTX. Application of Ba2+ enlarged FRCs and resonance at potentials below -80 mV, indicating that IK,ir normally attenuates resonance. Application of TTX greatly diminished resonance at potentials more depolarized than -65 mV, indicating that INaP normally amplifies resonance at these potentials. 7. The ZAP current input may be viewed as a model of oscillatory currents that arise in neocortical neurons during synchronized activity in the brain. We propose that the frequency selectivity endowed on neurons by IH may contribute to their participation in synchronized firing. The voltage dependence of the frequency-selective coupling between oscillatory inputs and spikes may indicate a novel mechanism for controlling the extent of low-frequency synchronized activity in the neocortex.
Hutcheon
B
B
Department of Pharmacology and Therapeutics, Faculty of Medicine, University of British Columbia, Vancouver, Canada.
Miura
R M
RM
Puil
E
E
D000818:Animals; D000831:Animals, Newborn; D066298:In Vitro Techniques; D007473:Ion Channels / Q000037:antagonists & inhibitors / Q000502:physiology*; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009044:Motor Cortex / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D019579:Neocortex / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D018408:Patch-Clamp Techniques; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000502:physiology; D024661:Potassium Channels, Inwardly Rectifying; D051381:Rats; D017207:Rats, Sprague-Dawley; D026941:Sodium Channel Blockers; D015222:Sodium Channels / Q000502:physiology; D013003:Somatosensory Cortex / Q000166:cytology / Q000187:drug effects / Q000502:physiology
D007473:Ion Channels; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D026941:Sodium Channel Blockers; D015222:Sodium Channels