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PD-1 deficiency disrupts in vivo neural activity in mouse Hippocampus and cortex
Minghui Hu1, Cui Lv2, Jianping Zhu3
1Key Laboratory of Traditional Chinese Medicine Classical Theory, Ministry of Education, Shandong University of Traditional Chinese Medicine, Jinan, China; Shandong Provincial Engineering Research Center for the Prevention and Treatment of Major Brain Diseases with Traditional Chinese Medicine (PTMBD), Shandong University of Traditional Chinese Medicine, Jinan, China; Chinese Medicine and Brain Science Interdisciplinary Research Center (CMBS), Shandong University of Traditional Chinese Medicine, Jinan, China.
Abstract:
Programmed cell death 1 (PD-1), encoded by the Pdcd1 gene, was identified as a target in cancer immunotherapy but may result in the overactivation of T cell function and emotional changes such as anxiety. The dynamic changes in neuronal activity related to the anxious status caused by Pdcd1-/- remain unclear. In this study, we addressed these physiological issues by simultaneously recording neuronal activity (spikes) and local field potentials (LFPs) in the medial prefrontal cortex (mPFC) and hippocampal CA3 region using in vivo multi-channel electrodes. Our results demonstrate that PD-1 deficiency induces anxiety-like behaviours and extensive neuronal firing disorders in the mPFC and CA3 regions of mice. The key finding was that in pyramidal neuron and interneurons in the CA3 region, the in vivo firing and spike-LFP encoding was disordered in the opposite direction by Pdcd1-/-. These changes leaded to abnormal oscillations in mPFC and CA3 and disturbed mPFC neuronal firing. Targeting the activation of excitatory neurons in CA3 regions could rescue anxiety-like behaviours in Pdcd1-/- mice. This study provides physiological insights into the dynamic cooperation mechanisms between the mPFC and CA3 circuits in anxiety-like behaviours caused by Pdcd1-/- and other mental disorders associated with autoimmune problems.
Insights
Programmed cell death 1 (PD-1) deficiency in mice causes anxiety and neuronal firing disorders. Targeting CA3 excitatory neurons may reverse these anxiety-like behaviors.
Area of Science:
- Neuroscience
- Immunology
- Behavioral Science
Background:
- Programmed cell death 1 (PD-1) is an immunotherapy target, but its deficiency can cause anxiety.
- The neural mechanisms underlying PD-1 deficiency-induced anxiety are not fully understood.
Purpose of the Study:
- To investigate the dynamic changes in neuronal activity in the medial prefrontal cortex (mPFC) and hippocampus (CA3) associated with anxiety in Programmed cell death 1 knockout mice (Pdcd1-/-).
- To explore the role of mPFC-CA3 circuit cooperation in anxiety-like behaviors.
Main Methods:
- Simultaneous in vivo recording of neuronal spikes and local field potentials (LFPs) in the mPFC and CA3 regions of Pdcd1-/- mice.
- Assessment of anxiety-like behaviors.
- Targeted activation of excitatory neurons in the CA3 region.
Main Results:
- PD-1 deficiency induced significant anxiety-like behaviors and widespread neuronal firing abnormalities in the mPFC and CA3.
- Spike-LFP encoding in CA3 neurons (types A and C) showed opposite imbalances in Pdcd1-/- mice.
- Activation of CA3 excitatory neurons ameliorated anxiety-like behaviors in Pdcd1-/- mice.
Conclusions:
- PD-1 deficiency disrupts neuronal activity in the mPFC and CA3, contributing to anxiety-like behaviors.
- Imbalanced spike-LFP encoding in the CA3 region is a key feature of PD-1 deficiency-induced anxiety.
- Targeting CA3 excitatory neurons offers a potential therapeutic strategy for anxiety associated with PD-1 dysfunction.
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