Timing-dependent modulation of working memory by VTA dopamine release in medial prefrontal cortex

Chaofan Ge, Zhaoqin Chen, Fangmiao Sun, Ruiqing Hou, Hongmei Fan, Yulong Li, Chengyu T. Li
2023 · doi:10.1101/2023.09.01.555676
preprint OA: closed CC-BY-NC-ND-4.0
📄 Open PDF View at publisher

Abstract

SUMMARY Dopamine significantly modulates working memory (WM) 1–8 , a fundamental cognitive function that maintains information during a brief delay period 9–11 . The temporal precision of dopaminergic modulation in WM and related neural mechanisms remain elusive. Here we unveiled the pivotal role of dopamine timing in WM performance with head-fixed mice engaged in learning an olfactory WM task. Through electrophysiology and optogenetics, we found that dopaminergic neurons in the ventral tegmental area (VTA) could encode WM information during the delay period, and manipulating dopaminergic neuronal activity bidirectionally modulated WM performance in an inverted U-shaped manner. Optogenetic manipulation of VTA activity also induced bidirectional changes in WM-related neural activity in the medial prefrontal cortex (mPFC). Imaging with a dopamine-sensitive GPCR-activation-based sensor (GRAB DA ) 12,13 revealed transient dopamine peaks in the mPFC specifically during the early-delay period. Optogenetic stimulation of VTA-to-mPFC dopaminergic projections during the early- and late-delay period enhanced and impaired WM performance, respectively. Manipulations outside these periods or involving the nucleus accumbens had no effect. Single-unit recordings demonstrated that optogenetic excitation of VTA-to-mPFC projections could modulate mPFC neuronal activity in a manner consistent with behavioral modulation. Thus, the timing of dopamine release is critical in modulation of neuronal activity and behavior.

My notes (saved in your browser only)

Citation neighborhood (no data yet)

We don't have any in-corpus citations linked to this paper yet. The paper's references may be in our DB but unresolved to ``paper_id`` (resolution happens at ingest when the cited DOI matches a row we already have). Run the cross-source citation reconcile pass to retry.

References (66)

Source provenance

crossref
last seen: 2026-07-13T06:45:31.467121+00:00
europepmc
last seen: 2026-05-19T01:45:01.086888+00:00
unpaywall
last seen: 2026-05-22T02:00:06.705733+00:00
License: CC-BY-NC-ND-4.0