bioRxiv Science⌕ Search

Biology subjects

Poh, E. Z.

Publications and source records attributed to Poh, E. Z..

2 recordsLinked to original sources

Ventromedial striatal dopamine dynamically integrates motivated action and reward proximity

Dopamine release in the ventromedial striatum (VMS) both invigorates actions and encodes reward-related information, yet how these functions are integrated remains under active debate. To investigate this further, we designed four different versions of a rat Go/No-go task, where we systematically manipulated response requirements, temporal task demands, and controllability of reward pursuit. Dopamine release increased reliably during action initiation (Go) but was delayed during action suppression (No-go), and this difference was insensitive to augmented response demands or controllability. Following response completion, dopamine rose gradually until animals arrived at the reward location, irrespective of reward-delivery timing, prior action demands, or controllability. This proximity dopamine-signal was exaggerated after animals exhibited Pavlovian consummatory behavior during No-go trials, revealing a motivational signal component. Together, these findings indicate that in reward contexts, VMS-dopamine signals successively integrate the invigoration of action initiation with the continuous tracking of spatial - but not temporal - proximity to rewards.

neuroscience↗

Low intensity repetitive transcranial magnetic stimulation modulates brain-wide functional connectivity to promote anti-correlated activity

BackgroundRepetitive transcranial magnetic stimulation (rTMS) induces action potentials to induce plastic changes in the brain with increasing evidence for the therapeutic importance of brain-wide functional network effects of rTMS; however, the influence of sub-action potential threshold (low-intensity; LI-) rTMS on neuronal activity is largely unknown. HypothesisWe investigated whether LI-rTMS modulates neuronal activity and functional connectivity. We also specifically assessed modulation of parvalbumin interneuron activity. MethodsWe conducted a brain-wide analysis of c-Fos, a marker for neuronal activity, in mice that received LI-rTMS to visual cortex. Mice received single or multiple sessions of excitatory 10Hz LI-rTMS with custom rodent coils or were sham controls. We assessed changes to c-Fos positive cell densities and c-Fos/parvalbumin co-expression. Peak c-Fos expression corresponded with activity during rTMS. We also assessed functional connectivity changes using brain-wide c-Fos-based network analysis. ResultsLI-rTMS modulated c-Fos expression in cortical and subcortical regions. c-Fos density changes were most prevalent with acute stimulation, however chronic stimulation decreased parvalbumin interneuron activity, most prominently in the amygdala and striatum. LI-rTMS also increased anti-correlated functional connectivity, with the most prominent effects also in the amygdala and striatum following chronic stimulation. ConclusionLI-rTMS induces changes in c-Fos expression that suggest modulation of neuronal activity and functional connectivity throughout the brain. Our results suggest that LI-rTMS promotes anticorrelated functional connectivity, possibly due to decreased parvalbumin interneuron activation induced by chronic stimulation. These changes may underpin therapeutic rTMS effects, therefore modulation of subcortical activity supports rTMS for treatment of disorders involving subcortical dysregulation. Highlights- Low-intensity rTMS increases brain-wide anti-correlated functional connectivity - Acute excitatory LI-rTMS modulates cortical and subcortical neuronal activity - Decreased parvalbumin interneuron activity may promote anti-correlated activity - Striatum and amygdala show prominent modulation with LI-rTMS

neuroscience↗