Role of anterior cingulate cortex inputs to periaqueductal gray for pain avoidance

Optogenetic fMRI for Brain-Wide Circuit Analysis of Sensory Processing

“…Based on previous ofMRI studies [ 14 , 15 , 16 , 17 , 18 , 19 , 20 ], three different optogenetic fMRI strategies can be adopted ( Figure 2 ): Optogenetic excitation of excitatory cell bodies (soma), which is the most common, or axon terminals to map cell-type-specific functional downstream or circuit-specific networks. Optogenetic silencing by excitatory opsins in inhibitory interneurons or inhibitory opsins in excitatory pyramidal neurons to measure spontaneous (resting-state) activity in the stimulation site and downstream resting-network strength.…”

“…Silencing ofMRI combined with electrical stimulation ( d ). Adapted with permission from Lee et al (2022) [ 20 ]. ACC; anterior cingulate cortex, PAG; periaqueductal gray.…”

“…In a specific example study, AAV-CaMKII-ChR2 was injected into the anterior cingulate cortex (ACC) ( Figure 2 (Ac)). Soma activation of ACC pyramidal neurons elicited a positive fMRI response in the ACC and its downstream regions including periaqueductal gray (PAG) [ 20 ]. Axon terminal activation of ACC-originating pyramidal neurons at PAG also induced a positive fMRI response in the stimulated site PAG and upstream ACC region.…”

“…Thus, the optogenetic activation of inhibitory neurons reduces excitatory neuronal activities and, consequently, fMRI signals at both the target site and its downstream regions ( Figure 2 (Bb)). Thus, ofMRI with neural silencing can determine the strength of interregional communication under basal conditions [ 17 , 19 , 20 ]. In the chronic pain model, indirect inhibition of the ACC pyramidal neurons (via VGAT-ChR2) enhanced negative BOLD responses in the ACC and its downstream regions ( Figure 2 (Bc)), suggesting that the chronic pain condition increases spontaneous neural activity in the ACC and enhances interconnected network strengths in downstream regions [ 20 ].…”

“…With ofMRI, we can investigate how a brain region interacts and modulates sensory processing ( Figure 2 (Cd)). For example, when optogenetic inhibition of the ACC was combined with electrical whisker pad stimulation, we were able to identify that the ACC modulated motor-related areas such as M1 and secondary motor cortex (M2) without affecting sensory areas such as S1 and VP [ 20 ]. Thus, sensory-evoked ofMRI is a novel and effective method for investigating the long-range circuit modulation of sensory processing.…”