Differences in Brain Microtubule Electrical Activity of the Hippocampus and Neocortex from the Adult Rat.

Brain waves are believed to reflect synchronized electrical oscillations produced by large groups of active neurons. These oscillations can be observed using electroencephalography (EEG) or local field potential (LFP) recordings. The presence of these waves in various animal phyla, including insects and vertebrates, suggests that they play a fundamental role in the brain's computational processes. Different types of brain waves are characterized by their frequency and amplitude. Examples include alpha, beta, delta, theta, and gamma waves, which exhibit distinct oscillatory activity patterns. Recent studies have emphasized the importance of wave coherence for various cognitive functions, particularly attention and memory. Increased coherence between specific brain regions is associated with improved attention performance, while reduced coherence is associated with attention deficits. Maintaining short-term memory requires coordinated activity between the prefrontal cortex and the hippocampus. Previous studies have shown that cytoskeletal polymers, including actin filaments and microtubules (MTs), have electrical properties that contribute to intracellular neuronal circuits and may interact with ion channels involved in neuronal activity. MTs in the brain generate spontaneous electrical oscillations with frequencies similar to brain waves, suggesting a central role in brain function. In this study, the authors used LFP measurements in conjunction with a patch-clamp system to investigate the presence of endogenous oscillations in specific regions of the adult rat brain. They detected specific patterns with distinct frequency peaks.

Rat brain tissue samples (n = 43), which were stored in an extracellular solution, were examined using a patch-clamp amplifier and a pipette electrode that was filled with an intracellular saline solution. (The solution contained an identical concentration of KCl in both the pipette and the bath.) To evaluate the impact of ion concentration on electrical currents, the tissue was incubated in a KCl solution for 24 to 48 hours. Then, the tissue was examined under symmetric KCl conditions using a patch-clamp amplifier as before. To evaluate the role of microtubules (MTs) in electrical oscillations of the rat brain, the authors examined the impact of paclitaxel, an MT stabilizer that eliminates electrical oscillations in MT preparations.

Voltage-clamped cortex samples exhibited spontaneous, self-sustaining electrical oscillations that responded directly to the amplitude and polarity of the electrical stimulus. Similar results were obtained with hippocampus samples. The Fourier spectra showed a fundamental frequency of approximately 38 Hz for both cortex and hippocampus samples. This frequency was present at 0 mV, suggesting the presence of a chemical gradient between the brain tissue and the pipette's interior. The oscillation was more pronounced in cortex samples than in hippocampus samples. Voltage-clamped cortex samples incubated in KCl exhibited spontaneous, self-sustaining electrical oscillations that responded directly to the amplitude and polarity of the electrical stimulus. Similar results were obtained with hippocampus samples. The Fourier spectra showed a fundamental frequency of approximately 38 Hz for both types of samples (cortex and hippocampus). This oscillation frequency was also present at 0 mV. After incubation with KCl, the oscillations in the cortex and hippocampus samples were similar. Spontaneous electrical oscillations were significantly reduced (though still measurable) after the addition of paclitaxel, with nearly complete inhibition achieved in the hippocampus. These results suggest that microtubules (MTs) play a fundamental role in the intracellular oscillations observed in the rat brain. According to electron microscopic images, the longitudinal microtubules in the cortex appear less organized than those in the hippocampus. These electrical differences may correspond to the degree of order in microtubule arrangements, as suggested by related studies.

This study significantly advances our understanding of the role of microtubules in neuronal electrical oscillations. The microtubule-stabilizing agent paclitaxel interacts with binding sites within microtubules. The significant reduction of electrical oscillations in the cortex and hippocampus caused by paclitaxel highlights the critical role of microtubules in these oscillations. Previous studies by the authors' research group demonstrated that microtubule bundles isolated from bovine brains generate spontaneous, self-sustaining electrical oscillations with frequency components within the range of brain waves [1]. MT-driven electrical oscillations with distinct peaks around 38 and 90 Hz have previously been observed in honeybee brains, suggesting the intriguing possibility that MTs act as central oscillators in the brain [2]. These data imply that the cytoskeleton may mediate intracellular electrical signals, a phenomenon that could be crucial to brain tissue.

Editor’s note:

Microtubules are thought to act as biological waveguides. Due to their hollow, cylindrical structure and crystal lattice, they can conduct electromagnetic waves within cells. Their geometry, dielectric contrast, and symmetry are similar to those of artificial optical waveguides, such as fiber-optic cables. Microtubules are the first macromolecules whose electromagnetic behavior can be fully modeled. Since microtubules are connected to voltage-gated ion channels in the cell membrane, they are likely involved, either directly or indirectly, in the biological effects of (external) electromagnetic fields. (AT)

1. Gutierrez BC, Pita Almenar MR, Martínez LJ, Siñeriz Louis M, Albarracín VH, Cantero MD, Cantiello HF (2021). Honeybee brain oscillations are generated by microtubules. The concept of a brain central oscillator. Frontiers in Molecular Neuroscience, 14, 727025. https://doi.org/10.3389/fnmol.2021.727025

2. Scarinci N, Priel A, Cantero MD, Cantiello HF (2023). Brain microtubule electrical oscillations – Empirical Mode Decomposition analysis. Cellular and Molecular Neurobiology, 43(5), 2089 –2104. https://doi.org/10.1007/s10571-022-01290-9