Nicotinic acetylcholine receptors (nAChRs) are widely expressed throughout the brain and they are involved in the control of fundamental neural functions. One of the most common nAChR subtypes are heteromeric beta2-containing (beta2*) nAChRs. In the prefrontal cortex (PFC), beta2* nAChRs are expressed by different neuronal populations with different effects on behavior. To better understand functional role of beta2* nAChRs, we need to know which neuronal types in the PFC express them and what is the effect of these receptors on behavior. In the present project, we used FISH to map the expression of beta2 nicotinic subunit in individual neuronal populations in the mouse PFC. We have shown that beta2 subunit is expressed by all main neuronal types, including excitatory and inhibitory neurons, and the parvalbumin-positive interneurons showed the most prevalent expression. Then we have selected NPY- and 5HT3a-positive neurons and used CRISPR to induce a specific knockdown (KD) of beta2 nicotinic subunit in the PFC in the two populations. We subjected mice with the specific KDs to multiple behavioral tasks to test whether the beta2 KD in different neuronal populations leads to the same or different behavioral phenotype. We found that the beta2 KD in both populations led to increase in sociability. Furthermore, only the KD in NPY-positive neurons led to a decrease of anxiety-like behavior. We conclude that the behavioral phenotype depends on the targeted neuronal population and that a cell-type-specific targeting of beta2* nAChRs can be more precise and efficient in the control of pathological behavior.