Histamine Enhances Theta-Coupled Spiking and Gamma Oscillations in the Medial Entorhinal Cortex Consistent With Successful Spatial Recognition

Abstract

Encoding of spatial information in the superficial layers of the medial entorhinal cortex (sMEC) involves theta-modulated spiking and gamma oscillations, as well as spatially tuned grid cells and border cells. Little is known about the role of the arousal-promoting histaminergic system in the modification of information encoded in the sMEC in vivo, and how such histamine-regulated information correlates with behavioral functions. Here, we show that histamine upregulates the neural excitability of a significant proportion of neurons (16.32%, 39.18%, and 52.94% at 30 μM, 300 μM, and 3 mM, respectively) and increases local theta (4-12 Hz) and gamma power (low: 25-48 Hz; high: 60-120 Hz) in the sMEC, through activation of histamine receptor types 1 and 3. During spatial exploration, the strength of theta-modulated firing of putative principal neurons and high gamma oscillations is enhanced about 2-fold by histamine. The histamine-mediated increase of theta phase-locking of spikes and high gamma power is consistent with successful spatial recognition. These results, for the first time, reveal possible mechanisms involving the arousal-promoting histaminergic system in the modulation of spatial cognition.

A Sleep‐Specific Midbrain Target for Sevoflurane Anesthesia

“…Multiple-Channel Single Unit Recording: Multiple-channel single-unit recording in the midbrain EW region was in accordance with previous studies. [28,73] Adult C57BL/6J male mice (n = 16) were used for multiplechannel single-unit recording. The mice were housed with food and water available ad libitum before surgery.…”

“…Implantation of the electrode was described in previous study in detail. [28,73] Briefly, the electrode was slowly advanced into the targeted region by using a piezoelectric micromanipulator (Sensapex). Single-units were monitored during the surgery in real time to obtain the fine signal-to-noise ratio of spike activities.…”

“…Firing Frequency Analysis: Single-unit spike sorting using offline sorter software (version 3.0), as described in previous published work was conducted. [28,73] First, principal component analysis was conducted to extract and represent the first 2 principal components on a 2-dimensional plot of detected spike events. Waveforms with similar principal components were clustered using k-means clustering algorithm.…”

How Do Neurotransmitter Pathways Contribute to Neuroimaging Phenotypes?

“…We replicated previous findings (Hansen, Shafiei, et al, 2022) that the spatial distribution of histamine radiotracer (H3) significantly contributes to the power maps. Another study observed that histamine amalgamates local theta and gamma power in MEG (Chen et al, 2017). Histaminergic neurons in the brain serve multiple signalling pathways.…”

GABAergic synaptic transmission and cortical oscillation patterns in the primary somatosensory area of a valproic acid rat model of autism spectrum disorder

“…The detailed power spectrum density (PSD) analysis of EEG recordings was carried out using a pwelch.m function in MATLAB (MathWorks Inc.) as described previously (Pasquetti et al, 2019). The frequency bands were separated as follows: delta (1–4 Hz), theta (4–12 Hz; Chen et al, 2018; Estefan et al, 2021; Pasquetti et al, 2019; Schoepfer et al, 2020; Tort et al, 2009), beta (13–30 Hz), slow gamma (30–60 Hz) and fast gamma (60–100 Hz).…”