Transient dopamine response on medium spiny neuron subtypes in switching approach-avoidance outcomes against action bias - A framework for exploration in action selection

An ensemble of direct and indirect pathway medium spiny neurons (dMSN and iMSN), compete via their neural activity to drive the decision to approach or avoid an object, respectively. Dopamine acting as a reward prediction error (RPE) signal causes experience-dependent synaptic changes in dMSN and iMSN, thereby shifting the dominance of neural activity to approach or avoidance signalling. These changes create bias in the striatal neuronal ensemble and restrict the choice to approach or avoidance in further iterations. However, organisms often exhibit behaviour where they choose undesirable or exploratory actions in anticipation of future reward or avoid desirable actions in anticipation of future risk. These against-bias decisions or exploratory decisions are not accounted for by the existing neuronal framework. To bridge this gap, we postulate that transient motivational dopamine released from dopaminergic axons locally at sub-second timescales can cause temporary switch in dominance of neural activity between dMSN and iMSN leading to such adaptive decisions. By accounting for bias towards approach or avoidance or neither through synaptic weightages and accounting for differential affinity of DA to D1R and D2R, changes in dMSN and iMSN excitability at different levels of motivational dopamine was analysed. Furthermore, the spiking activity of striatal neuronal ensemble comprising of dMSN projecting directly and iMSN projecting indirectly onto the output nuclei of basal ganglia i.e. SNr neurons was simulated. This led to promising findings that demonstrate how SNr neuronal activity can generate outcomes that work against the cortico-striatal synaptic bias towards approach or avoidance. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=192 HEIGHT=200 SRC="FIGDIR/small/630270v2_ufig1.gif" ALT="Figure 1"> View larger version (33K): org.highwire.dtl.DTLVardef@fa322org.highwire.dtl.DTLVardef@9f27e1org.highwire.dtl.DTLVardef@f35d84org.highwire.dtl.DTLVardef@1808ed4_HPS_FORMAT_FIGEXP M_FIG C_FIG (Source: Created in BioRender. Anisetty, N. (2025) https://BioRender.com/a96f199)