Studying the response of neuronal networks to radiofrequency signals requires the use of a specific device capable of accessing and simultaneously recording neuronal activity during electromagnetic fields (EMF) exposure. In this study, a Microelectrode Array (MEA) that records the spontaneous activity of neurons is coupled to an open transverse electromagnetic (TEM) cell which propagates EMF. We characterize this system both numerically and experimentally at 1.8 GHz. Two MEA versions were compared, for the first time, to determine the impact of their design dissimilarities on the response to EMF. Macroscopic and microscopic measurements using respectively a fiber-optic probe and a temperature-dependent fluorescent dye (Rhodamine-B) were carried out. Results indicate that one MEA shows more stability toward the changes of the surrounding environment compared to the other MEA. Using a fiber-optic thermometer, the measured specific absorption rate (SAR) probe value in the center of the more stable MEA was 5.5±2.3 W/kg. Using a Rhod-B microdosimetry technique, the measured SAR value at the level of the MEA electrodes was 7.0±1.04 W/kg. SAR values are normalized per 1-W incident power. Due to the additional metallic planes and a smaller chip aperture, this new recording chip is steadier in terms of SAR and temperature stability allowing high exposure homogeneity as required during biological experiments. A typical neuronal activity recording under EMF exposure is reported.
Harnessing the power of suggestion to modulate response to psychedelics could enhance their therapeutic efficacy by helping to increase the likelihood of positive responses, including mystical-type experiences.
Background and Purpose
Gamma oscillations are fast rhythmic fluctuations of neuronal network activity ranging from 30 to 90 Hz that establish a precise temporal background for cognitive processes such as perception, sensory processing, learning, and memory. Alterations of gamma oscillations have been observed in schizophrenia and are suggested to play crucial roles in the generation of positive, negative, and cognitive symptoms of the disease.
Experimental Approach
In this study, we investigated the effects of the novel antipsychotic cariprazine, a D3‐preferring dopamine D3/D2 receptor partial agonist, on cholinergically induced gamma oscillations in rat hippocampal slices from treatment‐naïve and MK‐801‐treated rats, a model of acute first‐episode schizophrenia.
Key Results
The D3 receptor‐preferring agonist pramipexole effectively decreased the power of gamma oscillations, while the D3 receptor antagonist SB‐277011 had no effect. In treatment‐naïve animals, cariprazine did not modulate strong gamma oscillations but slightly improved the periodicity of non‐saturated gamma activity. Cariprazine showed a clear partial agonistic profile at D3 receptors at the network level by potentiating the inhibitory effects when the D3 receptor tone was low and antagonizing the effects when the tone was high. In hippocampal slices of MK‐801‐treated rats, cariprazine allowed stabilization of the aberrant increase in gamma oscillation power and potentiated resynchronization of the oscillations.
Conclusion and Implications
Data from this study indicate that cariprazine stabilizes pathological hippocampal gamma oscillations, presumably by its partial agonistic profile. The results demonstrate in vitro gamma oscillations as predictive biomarkers to study the effects of antipsychotics preclinically at the network level.
Cortical gamma oscillations are associated with cognitive processes and are altered in several neuropsychiatric conditions such as schizophrenia and Alzheimer’s disease. Since dopamine D3 receptors are possible targets in treatment of these conditions, it is of great importance to understand their role in modulation of gamma oscillations. The effect of D3 receptors on gamma oscillations and the underlying cellular mechanisms were investigated by extracellular local field potential and simultaneous intracellular sharp micro-electrode recordings in the CA3 region of the hippocampus in vitro. D3 receptors decreased the power and broadened the bandwidth of gamma oscillations induced by acetylcholine or kainate. Blockade of the D3 receptors resulted in faster synchronization of the oscillations, suggesting that endogenous dopamine in the hippocampus slows down the dynamics of gamma oscillations by activation of D3 receptors. Investigating the underlying cellular mechanisms for these effects showed that D3 receptor activation decreased the rate of action potentials (APs) during gamma oscillations and reduced the precision of the AP phase coupling to the gamma cycle in CA3 pyramidal cells. The results may offer an explanation how selective activation of D3 receptors may impair cognition and how, in converse, D3 antagonists may exert pro-cognitive and antipsychotic effects.
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