Browsing by Subject "electrophysiology"

Chronic stress has been linked to the pathogenesis of various disorders, such as generalized anxiety disorder, depression, and post-traumatic stress disorder (PTSD). Stress-induced hyperexcitability of the basolateral amygdala (BLA) has implications in anxiety-like behavior. Promising evidence points to the direction of GluK1 subunit containing kainate receptors (KARs) having a role in the modulation of GABAergic transmission in the lateral amygdala (LA). The aim of the present study was to investigate whether dysfunction of KARs contribute to stress-induced amygdala hyperexcitability and anxiogenesis in mice. Chronic restraint stress (CRS) is an animal model simulating chronic psychological stress. An in situ hybridization experiment was performed to investigate how CRS affects expression levels of GluK1 in the different neuronal populations in the LA. These data show that CRS leads to downregulation of GluK1 expression in the parvalbumin-positive (PV+) interneurons specifically. Patch clamp recordings of spontaneous inhibitory postsynaptic currents showed that CRS did not affect synaptic GABAergic transmission to the principal neurons in the LA. Lastly, conditional knock-out (cKO) mice that have the Grik1 gene knocked out selectively in the PV-expressing interneurons showed no change in anxiety-like behavior after CRS while their wild-type counterparts demonstrated an increase in anxiety-like behavior observable in the elevated plus maze test. Thus, ablation of GluK1 in PV+ interneurons affects the stress-induced anxiogenesis. Due to low number of animals, it cannot be confirmed yet whether the deletion leads to stress resilience or a phenotype where even regular handling is an aversive experience comparable to physical restraint. GluK1 KAR modulation of PV+ interneuron excitability and its susceptibility to stress-related alterations is only a recently discovered phenomenon, and even though this study provides some insight into the underlying mechanism, further research is needed. Systematic characterization of the mechanism could provide a novel tool for understanding and treating stress-related pathological anxiety, possibly helping patients suffering from anxiety disorders resistant to current treatments available.

Research conducted on neural oscillations have paved the way to unravel the complexities of the brain dynamics underlying behavior and cognition. Neuronal oscillations characterize neuronal activity and processing at all spatial scales from neuronal microcircuits to large-scale brain dynamics and hence link cellular and molecular mechanisms to circuit dynamics underlying behavior. Large-scale oscillations and their inter-areal synchronization can be identified from in vivo electrophysiological data from animal models as well as from human magneto- and electroencephalography (M/EEG) data. Large-scale oscillation dynamics identified from human M/EEG data has been critical for resolving whole-brain oscillation dynamics view but is hindered by the indirectness of the measures. In contrast, rodent in vivo electrophysiology has been conventionally used to resolve oscillation dynamics locally in brain microcircuits. Although these measurements yield critical information of the mechanisms behind local oscillation dynamics, they are difficult to link with whole-brain dynamics view obtained from human M/EEG data. The newly established setup at the Neuroscience Center aims overcome these limitations and allows the measurements directly from the brain of awake head-fixed mice with over 1000 channel measuring simultaneously from both cortical and subcortical structures. This Master’s thesis project objective was to obtain proof-of-concept data to characterize oscillation dynamics during resting-state (RS) from awake behaving mice and to investigate whether these dynamics could be modulated by the manipulating E/I balance. More specifically, the current project aimed to investigate the oscillatory profile of the default-mode network (DMN) activity while manipulating the E/I balance with pharmacological mediums. Electrophysiological data was collected from RS activity from awake mice with two µECoG grids comprising together 512 channels and two laminar Neuropixel probes with each consisting 348 channels. The areas of interest were targeted to capture the DMN activity, covering anterior cingulate cortex (ACC), secondary motor cortex (M2), retrosplenial areas, visual cortical layers, pre- and infralimbic areas, hippocampal areas such as CA1 and dentate gyrus as well as lateral and posterior thalamic areas. The network activity was modulated with pharmacological mediums (sedative, stimulant, control) administered in low acute doses to see their effects on the oscillatory profile. Data from four mice were included into this Master’s thesis work and each mouse was recorded first for 30-minute daily baseline, following a 30-minute pharmacological measurement. This Master’s thesis included the data obtained from the µECoG data to the data analysis focusing on the large-scale cortical activity of the DMN. Power spectral density analysis showed a prominent alpha peak, also seen in humans, across condition with a mild decrease in volume in the stimulant condition. Synchronization was assessed with imaginary part of the phase locking value (iPLV), and the results showed increased synchronization in the stimulant condition and decreased in sedative condition in comparison to the control condition. The amplitude correlation coefficient showed also expected results in both pharmacological conditions, namely higher correlation in stimulant and lower in sedative. This project was able to obtain valuable information of the newly established in vivo electrophysiology setup and the results were in line with our expectations. This promising outcome solidifies the translational potential of the setup and its ability to serve as a translational counterpart in numerous research designs in health and disease.