Activation of basolateral amygdala to anterior cingulate cortex circuit alleviates MK-801 induced social and cognitive deficits of schizophrenia

Abstract

IntroductionSchizophrenia is a severe psychiatric disorder with a high prevalence worldwide, however, its pathogenesis remains poorly understood.Methods and resultsIn this study, we used the non-competitive NMDA receptor antagonist MK-801 to induce schizophrenia-like behaviors and confirmed that mice exhibited stereotypic rotational behavior and hyperlocomotion, social interaction defects and cognitive dysfunction, similar to the clinical symptoms in patients. Here, the anterior cingulate cortex (ACC) and basolateral amygdala (BLA) were involved in the schizophrenia-like behaviors induced by MK-801. Furthermore, we confirmed BLA sent glutamatergic projection to the ACC. Chemogenetic and optogenetic regulation of BLA-ACC projecting neurons affected social and cognitive deficits but not stereotypic rotational behavior in MK-801-treated mice.DiscussionOverall, our study revealed that the BLA-ACC circuit plays a major role and may be a potential target for treating schizophrenia-related symptoms.

Chemogenetic attenuation of PFC pyramidal neurons restores deficits in recognition memory following adolescent NMDA receptor blockade

“…Previously we have shown that endocannabinoid enhancement reversed the early-adolescence MK-801-induced cognitive deficits via cannabinoid receptor 2 activation, and the social deficits via cannabinoid receptor 1 activation (Bauminger et al, 2022), highlighting that social and cognitive behaviors rely on different neural mechanisms. Social behavior abnormalities in the current model may be related to other circuits, such as the ventral tegmental area-nucleus accumbens pathway (Gunaydin et al, 2014) or the basolateral amygdala-anterior cingulate cortex pathway (Huang et al, 2022). Future studies should examine the ability to reverse the early-adolescence MK-801-induced social behavior abnormalities using chemogenetic tools in other cell types or neural circuits.…”

Dysfunction of the triple-network model is associated with cognitive impairment in patients with cerebral small vessel disease

“…A previous study indicated that patients with mild cognitive impairment exhibited altered whole-brain functional connectivity (FC) of the cingulate cortex, including decreased FC patterns in the ACC [ 44 ], similar to our results. Additionally, an experimental animal study showed that the activation of the ACC might alleviate cognitive deficits [ 45 ]. Furthermore, the disengagement of the DMN from the SN and CEN under high cognitive load was caused by reduced outflow signals from the PCC [ 43 ].…”

Neural circuits regulating visceral pain

“…The anterior part of the BLA has dense, direct and reciprocal connections with areas of the ACC 49 , 50 . The induction of synaptic plasticity is favored by the coordinated timing of action potentials across populations of neurons with rising oscillations of different frequencies, recorded as local field potentials (LFPs) 51 .…”