Optogenetic stimulation of cell bodies versus axonal terminals yields remarkably comparable activity and functional connectivity in the brain

Motivation: Optogenetic techniques are commonly used to dissect neural pathways with presumed specificity for targeted projections. Goal(s): To explore the effects of stimulating cell bodies versus a projection terminal in the ventral subiculum to nucleus accumbens shell pathway. Approach: Optogenetic fMRI was used to compare the effects of stimulating vSUB cell bodies and their terminals in NAcSh, analyzing brain activity and connectivity patterns. Results: Terminal stimulation induces brain activity and connectivity patterns similar to cell body stimulation, suggesting broader network engagement through antidromic activation. Impact: The fMRI findings from this study challenge the general assumption that optogenetic stimulation at synaptic terminals primarily recruits feedforward activity in downstream brain regions, urging the neuromodulation community to exercise caution in interpreting data obtained with terminal optogenetic approach.