INTRODUCTION: Among cortical inhibitory cells, activity of somatostatin interneurons (SST INTs) has been recently proposed as a key player in the formation of neuroplastic changes. Sensory deprivation causes changes in inhibitory systems that lead to disinhibition of the spared barrel, allowing for spreading of its functional representation. Because of their unique pattern of connectivity, we hypothesize that layer IV SST INTs strongly modulate disinhibition of the spared barrel, supporting the sensory deprivation‑induced plastic change formation. AIM(S): Using a chemogenetic approach, we aimed to study a direct role of layer IV SST INTs activity in plastic change formation induced by sensory deprivation in mice barrel cortex. METHOD(S): SST-Cre mice were unilaterally injected with Cre-dependent AAV2 vectors expressing inhibitory DREADDs into a single barrel of row C. Two weeks later, mice underwent a sensory deprivation paradigm, in which all whiskers but one, C3, on one side of the snout were plucked for a week. During deprivation, the activity of SST INTs was blocked by DREADDs activation with its agonist, CNO, continuously administered via Alzet® Osmotic Pumps. To visualize plastic change, [14C]‑2‑deoxyglucose brain mapping was performed. The area of functional representation of the spared whisker and contralateral one was compared. RESULTS: We found that SST INTs inhibition in the spared barrel did not influence the area of activation of the spared whisker compared to transduced animals with saline administration instead of CNO. However, SST INTs blockade in the deprived barrel, adjacent to the spared one, led to a dramatic decrease in functional plasticity of spared whisker representation. CONCLUSIONS: Our results indicate that layer IV SST INTs activity in deprived, but not spared barrel, is essential in sensory deprivation-induced plastic change formation in the barrel cortex of mice. FINANCIAL SUPPORT: Polish National Science Centre Grant to GD (2017/27/N/NZ4/02639).