Nonlinear computational models of dynamical coding patterns in depression and normal rats: from electrophysiology to energy consumption

Major depressive disorder (MDD) is one of the most serious neuropsychiatric disorders. Exploring the pathogenesis and dynamical coding patterns of MDD can provide new targets for clinical drug treatment and new ideas for the research of other neuropsychiatric and neurodegenerative diseases. We selected the medium spiny neuron (MSN) of nucleus accumbens (NAc) as the research objective. NAc is located in the dopaminergic pathway, regulating rewards, emotions and other behaviors. Abnormalities in these behaviors are considered as the main clinical symptoms of MDD. We simulated the different spike patterns of MSNs in MDD group and control group by dynamical Hodgkin-Huxley model. The simulated results can match the electrophysiological experiments, which occurred due to following reasons: (1) The external stimulus current of MDD group was amplified by the local neural microcircuit; (2) the selective permeability to sodium was abnormally decreased; and (3) the dopamine D2 receptor signaling pathway was abnormal in the MDD group. Furthermore, we proposed a dynamical energy model, and the energy results demonstrated that the energy cost in MDD group was lower, which led to persistent depression in patients with MDD. Simultaneously, the negative-to-total energy ratio of MSN in MDD group was higher than that in control group, and the delay time of the power peak and the potential peak in MDD group was shorter than that in the control group. The results showed that the abnormal firing patterns were the direct cause of abnormal behaviors of MDD and indicated that subthreshold activities of MDD group were more intense.

Automated summary

Investigating the pathogenesis and firing patterns of neurons in major depressive disorder (MDD) has implications for clinical treatment and understanding other neuropsychiatric and neurodegenerative diseases. Simulation and energy analysis revealed that abnormal firing patterns of neurons contribute to the abnormal behaviors in MDD.