Improvement of activation of parvalbumin positive inhibitory neurons to memory impairment caused by frontal cortex ischemia

Abstract

Objective To determine the effect of activating parvalbumin (PV) positive inhibitory neurons on memory impairment caused by frontal cortex ischemia and analyze the related mechanism. Methods Adult PV-Cre mice were randomly divided into control group [frontal cortex injection of 0.9% NaCl+ intraperitoneal injection of clozapine N-oxide hydrochloride (CNO)], model group (frontal cortex injection of endothelin+intraperitoneal injection of 0.9% NaCl) and intervention group (prefrontal cortex injection of endothelin+intraperitoneal injection of CNO). Among them, virus microinjection technology was adopted to specifically express mCherry in the PV neurons in the frontal cortex of mice from the control group, while specifically express hM3d-mCherry in the PV neurons from the model group and the intervention group. Injection of CNO was performed in the intervention group to specifically activate PV positive neurons through hM3d. The memory and motor functions of mice were detected by T-maze and object location and recognition tasks. The changes of dendritic spine density of pyramidal neurons in frontal cortex were analyzed by Golgi staining. Results The administration of endothelin in frontal cortex caused local ischemia. Compared with the normal control group, the density of dendritic spines on pyramidal neurons was decreased after frontal cortex ischemia, resulting in the decrease of selection accuracy in T-maze and exploration scores in object location and recognition tasks (P < 0.01). On the contrary, activation of PV positive neurons significantly increased the density of dendritic spines in frontal cortex, and significantly improved the selection accuracy of mice in T-maze test (P < 0.05) and the exploration score in object location and recognition tasks (P < 0.05). Conclusion Activation of PV positive neurons can improve memory impairment caused by frontal cortex ischemia, which may be related to increasing the density of dendritic spines in frontal cortex.

Keywords

• frontal cortex
• pv positive neurons
• memory