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Regulation of micturition reflex by neural activity in the anterior cingulate cortex

望月 孝規 山梨大学 DOI:info:doi/10.34429/00004866

2020.12.17

概要

【Introduction】
　Previous studies have suggested that anterior cingulate cortex (ACC) might be involved in mict urition. However, the mechanism has not been fully elucidated in comparison to pontine micturit ion center (PMC) and periaqueductal gray matter (PAG), which are the same cerebral regions found to be involved in micturition reflex. The purpose of this study is to clarify how ACC neu ronal activity contributes to the micturition reflex.

【Materials & Methods】
　1. Neuronal tracers cholera toxin subunit B (CTB) and wheat germ agglutinin (WGA) were injected into the PAG, ACC, and bladder of wild type (WT) mice to confirm the distribution of projection targets. 2. Under urethane anesthesia, WT mouse ACC was stimulated and inhibited nonselectively measuring the bladder pressure using electrical stimulation and drug administration. 3. Optogenetic selective stimulations for excitatory neurons in ACC were performed using thymus cell antigen1-channelrhodop sin-2 (Thy1ChR2) mouse and adeno-associated viruses-calcium/calmodulin-dependent kinase II- channelrhodopsin-2 (AAV-CaMK2-ChR2) with WT mouse. Furthermore, optogenetic selective stimulations for parvalbumin (PV) neurons that is one of the inhibitory neurons were performed using PV-Cre mouse with adeno-associated viruses- double-floxed inverted orientation- channelrhodopsin-2 (AAV-DIO-ChR2). 4. To map cortical regions inducing micturition reflex, Thy1ChR2 mice were used, and photostimulation at multiple sites over the cerebral cortex were performed and the changes of the bladder pressure were measured.

【Results】
　1. The presence of fluorescence was confirmed in ACC, PAG, PMC, and the bladder. 2. Non-s elective activation of ACC neural activity promoted the micturition reflex. On the other hand, no n-selective inhibition suppressed bladder contraction. 3. While selective stimulation of ACC excit atory neurons promoted the micturition reflex, photostimulation of PV neurons suppressed it. 4. Although photostimulation of the ACC excitatory neurons had a higher effect on an increase of bladder pressure, this effect was attenuated as the photostimulation point moved laterally.

【Discussion】
　The presence of a projection pathway from ACC to the bladder via PAG and PMC was confir med. In fact, manipulation of ACC neural activity had a direct effect on the micturition reflex. S pecifically, activation of ACC neural activity by nonselective stimulation facilitated the micturition reflex, while nonselective inhibition suppressed it.
　Selective stimulation using optogenetics for ACC excitatory neurons induced micturition reflex. On the other hand, selective stimulation for ACC PV neurons suppressed bladder contraction. These results showed that selective stimulation of each of the neurons with different functions i n the ACC could control the micturition reflex.
　Compared to other cortical areas, ACC neural activity has a strong effect on the micturition refl ex. It has been thought that micturition is controlled by the interaction between regions of the cerebrum, such as the PMC and PAG. However, it was found that selective activation of neuro ns with different functions in a single region, which is ACC, also controlled micturition reflex in this study.

【Conclusion】
　ACC neuronal activities play a crucial role in the initiation of micturition. The neuronal balance of excitation and inhibition in ACC could regulate micturition reflex.

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