UNCOVERING THE NEURAL CIRCUIT MECHANISMS OF CHOICE SELECTION: MANIPULATING THE DYNAMICS OF CHOICE ENGRAM COMPETITION IN THE MOUSE PREFRONTAL CORTEX

Decision making is a fundamental cognitive process that ranges from simple daily choices to complex, life-changing decisions. In perceptual decision making, incoming sensory information is evaluated in light of prior experience to estimate the potential outcomes of alternative actions. According to prevailing computational models, decisions emerge from the dynamic competition between these choice-selective ensembles. This winner-take-all dynamics between choice ensembles is readily implemented by attractor networks in which recurrent excitation and inhibitory interactions stabilize one option while suppressing alternatives. Despite strong theoretical frameworks, direct experimental tests of how competing choice ensembles interact to determine behavioral outcomes remain limited. Building on previous evidence showing robust choice-specific encoding in the anterolateral motor cortex (ALM), we combined the three-choice visuospatial delayed-response task with engram-labeling and manipulation in ALM to investigate the causal role of ensemble competition in decision making. We interrogated these dynamics through two complementary manipulations: first, by unspecific silencing of ALM, obtained by exciting inhibitory interneurons to suppress all choice-ensembles. Second, by selectively exciting or inhibiting the memory engrams corresponding to specific choices. Our analysis shows that excitation of a specific choice ensemble disrupted the selection of the associated choice without a significant effect on the competing representations. Together, these findings suggest that perturbing excitatory–inhibitory balance and directly manipulating choice-specific ensembles alters the relative stability of attractor states, thereby biasing choice selection. Our results provide a mechanistic characterization of the competition between neural ensembles, an essential component in the choice selection dynamics.