Modulation of Frequency Preference in Heterogeneous Populations of Theta-resonant Neurons

Neurons from several brain regions resonate in the theta frequency range (4–12 Hz), displaying a higher voltage response to oscillatory currents at a preferred ‘resonant’ frequency (f_R). Subthreshold resonance could influence spiking and contribute to the selective entrainment of neurons during the network oscillatory activity that accompanies several cognitive processes. Neurons from different regions display resonance in specific theta subranges, suggesting a functional specialization. Further experimental work is needed to characterize this diversity and explore how frequency preference could be dynamically modulated. Theoretical studies have shown that the fine-tuning of resonance depends in a complex way on a variety of intrinsic factors and input properties, but their specific influence is difficult to dissect in cells. We performed slice electrophysiology, dynamic clamping and modelling to assess the differential frequency preference of rat entorhinal stellate neurons, hippocampal CA1 pyramidal neurons and cortical amygdala neurons, which share a hyperpolarization-activated current (I_h)-dependent resonance mechanism. We found heterogeneous resonance properties among the different types of theta-resonant neurons, as well as in each specific group. In all the neurons studied, f_R inversely correlated with the effective input resistance (R_in), a measurable variable that depends on passive and active membrane features. We showed that resonance can be adjusted by manipulations mimicking naturally occurring processes, as the incorporation of a virtual constant conductance or cell depolarization, in a way that preserves the f_R-R_in relationship. The modulation of frequency selectivity influences firing by shifting spike frequency and timing, which could influence neuronal communication in an active network.