A midbrain–cortical circuit mediated by a claustrum neuronal ensemble orchestrates drug-paired context memory processing
Ziheng Zhao, Yuhong He, Yang Liu, Quying Feng, Hee Young Kim, Yu Fan, Xiaowei Guan
Ziheng Zhao, Yuhong He, Yang Liu, Quying Feng, Hee Young Kim, Yu Fan, Xiaowei Guan
View: Text | PDF
Research Article Neuroscience Public Health

A midbrain–cortical circuit mediated by a claustrum neuronal ensemble orchestrates drug-paired context memory processing

Abstract

Drug-associated environmental cues can trigger drug-seeking behavior and precipitate relapse. In this study, we determined that the claustrum (CL) connects the ventral tegmental area (VTA) with the medial prefrontal cortex (mPFC), forming the VTA–CL–mPFC circuit. Using a methamphetamine (METH) conditioned place preference (CPP) model in male mice, we found that manipulating the VTA–CL–mPFC circuit or CL neuronal ensemble receiving projections from VTA and projecting to mPFC (VTA–CL–mPFC) could disrupt the retrieval of METH-paired context memory, resulting in the blockage of the acquisition of METH CPP in male mice. During the process, dopamine release and dopamine 1-like receptor–mediated activation of CL neurons were required for the retrieval of METH-induced reward memory in male mice. These findings reveal a midbrain–cortical circuit orchestrated by CL neurons that plays an essential role in the retrieval of drug-paired environmental cue memory.

Authors

Ziheng Zhao, Yuhong He, Yang Liu, Quying Feng, Hee Young Kim, Yu Fan, Xiaowei Guan

×

Figure 1

The VTATH–CLGlu–mPFC circuit and the VTA–CL–mPFC neuronal ensemble.

Options: View larger image (or click on image) Download as PowerPoint
The VTATH–CLGlu–mPFC circuit and the VTA–CL–mPFC neuronal ensemble. (A) ...
(A) Schematic of viral transfection. (B) Representative image of tdTomato+ neurons in VTA. (C) Schematic of viral transfection. (D) Representative images of mGFP+mRuby+ axon terminals around CLGlu neurons. (E) Schematic of viral transfection. (F) Representative images of CTB-555+TH+ neurons in VTA. (G) Schematic of viral transfection. (H) Heatmap of DA3h fluorescence (left), quantification (middle), and AUC (right) of ΔF/F in CL. n = 4 mice/group. (I) Schematic of viral transfection. (J) Example traces and quantification of the number of APs. n = 6 cells from 6 mice/group. (K) Schematic of viral transfection. (L) Representative images of mRuby+ axon terminals in mPFC. (M) Schematic of viral transfection. (N) Representative images of CaMKII+mCherry+ neurons in CL. (O) Schematic of viral transfection. (P) Example traces and quantification of the amplitude of EPSCs. n = 5 cells from 6 mice/group. (Q) Schematic of viral transfection. (R) Representative images of EGFP+ neurons in CL and EGFP+ axon terminals in mPFC. (S) Schematic of viral transfection. (T) Representative images of EGFP+ neurons in CL. NS, P > 0.05, *P < 0.05, **P < 0.01. Two-way ANOVA with Šidák’s multiple-comparison test (H and J); 2-tailed paired t test (P). Scale bars: 100 μm (B, D, F, L, N, R, and T).