Tonic current through GABAA receptors and hyperpolarization-activated cyclic nucleotide-gated channels modulate resonance properties of rat subicular pyramidal neurons.

The subiculum, considered to be the output structure of the hippocampus, modulates information flow from the hippocampus to various cortical and sub-cortical areas such as the nucleus accumbens, lateral septal region, thalamus, nucleus gelatinosus, medial nucleus and mammillary nuclei. Tonic inhibitory current plays an important role in neuronal physiology and pathophysiology by modulating the electrophysiological properties of neurons. While the alterations of various electrical properties due to tonic inhibition have been studied in neurons from different regions, its influence on intrinsic subthreshold resonance in pyramidal excitatory neurons expressing hyperpolarization-activated cyclic nucleotide-gated (HCN) channels is not known. Using pharmacological agents, we show the involvement of α5ßγ GABAA receptors in the picrotoxin-sensitive tonic current in subicular pyramidal neurons. We further investigated the contribution of tonic conductance in regulating subthreshold electrophysiological properties using current clamp and dynamic clamp experiments. We demonstrate that tonic GABAergic inhibition can actively modulate subthreshold properties, including resonance due to HCN channels, which can potentially alter the response dynamics of subicular pyramidal neurons in an oscillating neuronal network.

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 (fR). 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 (Ih)-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, fR inversely correlated with the effective input resistance (Rin), 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 fR-Rin relationship. The modulation of frequency selectivity influences firing by shifting spike frequency and timing, which could influence neuronal communication in an active network.