Local Generation of Theta-Frequency EEG Activity in the Parasubiculum

Abstract

The parasubiculum is a major component of the hippocampal formation that receives inputs from the CA1 region, anterior thalamus, and medial septum and that projects primarily to layer II of the entorhinal cortex. Hippocampal theta-frequency (4 -12 Hz) electroencephalographic (EEG) activity has been correlated with sensorimotor integration, spatial navigation, and memory functions. The present study was aimed at determining if theta is also generated locally within the parasubiculum versus volume conducted from adjacent structures. In urethan-anesthetized rats, the phase-reversal of theta activity between superficial and deep layers of the parasubiculum was demonstrated using differential recordings from movable bipolar electrodes that eliminate the influence of volume-conducted activity. Parasubicular theta was abolished by atropine, and was in phase with theta in stratum radiatum/lacunosum-moleculare of the CA1 region. Whole cell current-clamp recordings in brain slices were then used to determine if parasubicular theta may be generated in part by membrane potential oscillations in layer II neurons. Membrane potential oscillations occurred in most layer II neurons, including four putative interneurons, when cells were held at near-threshold voltages using current injection. The frequency of oscillations increased from 3.2 to 6.1 Hz when bath temperature was raised from 22 to 32°C, and oscillations persisted in the presence of blockers of fast ionotropic glutamatergic and GABAergic synaptic transmission. Oscillations are therefore likely generated by intrinsic, voltage-dependent ionic conductances. These results indicate that theta field activity is generated locally within the parasubiculum and that intrinsic membrane potential oscillations, synchronized by local inhibitory inputs, may contribute to the generation of this activity.

Conductances Mediating Intrinsic Theta-Frequency Membrane Potential Oscillations in Layer II Parasubicular Neurons

“…Methods used for in vitro recordings were similar to those in previous reports (Chapman and Lacaille 1999b;Glasgow and Chapman 2007) and were conducted in accordance with guidelines of the Canadian Council on Animal Care. Acute brain slices were obtained from 4-to 6-wk-old male Long Evans rats (Charles River, Montreal, Quebec, Canada).…”

“…Cells of the superficial layers of the parasubiculum were visualized using an upright microscope (Leica, DM-LFS) equipped with a long-range water immersion objective (ϫ40), differential interference contrast optics, and a near-infrared camera (COHU). The borders of the superficial layers of the parasubiculum were delineated using criteria described previously (Funahashi and Stewart 1997b;Glasgow and Chapman 2007). Layer II of the parasubiculum contains relatively large principal neurons and is diffuse and disorganized compared with the relatively compact superficial layers of the medial entorhinal cortex and presubiculum (Amaral and Witter 1989;Funahashi and Stewart 1997a,b).…”

“…Using whole cell current-clamp recordings in acute brain slices, we previously found that depolarization to near-threshold voltages resulted in theta-frequency membrane potential oscillations in ϳ80% of layer II parasubicular neurons (Glasgow and Chapman 2007). The oscillations persisted in the presence of synaptic blockers and were blocked by hyperpolarization, indicating that they are driven by intrinsic, voltagedependent conductances.…”

“…Low-amplitude theta activity was recorded near the parasubiculum in early mapping studies (Bland and Whishaw 1976), but because this activity might have been volume-conducted from adjacent structures, we recently used depth profiles with moving bipolar electrodes in urethanized rats to verify that theta-frequency EEG activity is generated locally within the superficial layers of the parasubiculum (Glasgow and Chapman 2007). The presence of place cells in the parasubiculum suggests that the region contributes to spatial navigation (Hargreaves et al 2005(Hargreaves et al , 2007Taube 1995), and a substantial proportion of these cells fire with a consistent phase-relation to theta activity (Cacucci et al 2004;Taube 1995).…”

Anterior thalamic lesions alter both hippocampal-dependent behavior and hippocampal acetylcholine release in the rat

“…In addition, it has recently been demonstrated that the AV nuclei are entrained to hippocampal theta activity (Vertes et al 2001;Tsanov et al 2011). Theta-frequency (4 -12 Hz) activity within the hippocampus and associated regions are modulated by the MS region and are correlated with successful spatial navigation and memory functions (Glasgow and Chapman 2007). Such results have led some to conclude that the AV nuclei are part of a MS theta system that modulates neural activation within the extended hippocampal system Vertes et al 2004).…”