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Researchers optically simulate anxiety-like behavior with tachycardia

Using a micro-light-emitting display (LED) harness and systemic channelrhodopsin delivery, researchers recently designed a non-invasive optogenetic and wearable cardiac pacemaker for precise and specific modulation of cardiac rhythm for up to 900 beats per minute (bpm).

Anxiety has been linked in studies to an increase in heart rate. It’s unclear, though, whether tachycardia can cause worry. Prior research by the researchers showed that ChRmine permitted non-invasive neurological regulation of deep cerebral circuits, opening the door to optogenetic control of cardiac tissues in humans.Researchers created a pacemaker for non-invasive optogenetic control of specific cardiac rhythms during active-type behavior in the current study.

In order to pinpoint the areas of the brain that were activated by the enforced optogenetic heart rhythms, brain-wide activity were screened and electrophysiological investigations were carried out. ChRmine was put under the control of the murine cardiovascular troponin T promoter (mTNT), using the AAV9 cardio-trophic serological type, to achieve cardiomyocyte-limited expression.

To determine if systemic ChRmine administration would enable non-invasive optogenetic regulation of cardiac rhythms, wild-type mouse mice were used. Wearable fabric vests with a 591.0 nm micro-LED placed on them were used to illuminate the chest wall’s flesh. Intermittent ventricular tachycardia of 900 beats per minute for 500 seconds was used to test the hypothesis that the cardiac pacemaker’s imposed cardiac rhythms might influence behavior.

Assessing the aversive or appetitive impact of optogenetic heart pacing was done using real-time place preference (RTPP) tests, and measuring anxiety-related behavior was done using elevated plus maze (EPM) assays. The team also used modified Vogel conflict tasks to examine if the context-based rise in anxiety-related behavior would be seen during traditional operant tasks. Despite the fact that the rewards came with shock risks, mice with limited access to water were nevertheless able to seek out water.

For whole-brain screening, transgenic TRAP2 murine animals were used. These animals included neurons with increased Fos expression that could be tagged with the tdTomato neural activation marker. Awake mouse animals were used in in vivo electrophysiological tests to evaluate optogenetic cardiac control-imposed brain dynamics at the single-neuron level. Furthermore, optogenetic cardiac inhibition was carried out employing inhibitory-type.Optically induced intermittent ventricular tachycardia potently increased anxiety-associated behavior, crucially in risky-type contexts only, indicative of brain (central) and body (peripheral) involvement in emotional development. The posteriorly located insular cortical region (pIC) was identified as a probable regulator of bottoms-up heart interoceptive-type processing, the optogenetic blockade of which suppressed anxiety-associated behavior initially induced by optogenetic cardiovascular pacing.