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Peer-reviewedCC BY-NC-ND 4.0Brain Structure & Function

Abstinence from heroin self-administration increases dendritic spine head diameter and the proportion of mushroom spines in rat prelimbic cortical neurons projecting to the paraventricular thalamus

  1. 1Department of Integrative Physiology and Neuroscience, Washington State University, Pullman, WA 99164 USA

Abstract

Relapse to opioid use remains the principal obstacle to recovery, often driven by enduring neuroadaptations that sustain vulnerability across abstinence. We have previously shown that the projection from the rat prelimbic cortex (PL) to the paraventricular thalamus (PVT) is functionally potentiated following abstinence from heroin self-administration and is necessary for cued heroin seeking, yet whether this pathway undergoes structural remodeling remains unknown. Using an intersectional viral strategy to selectively label PL neurons projecting to the PVT in rats, we reconstructed their apical tuft dendritic spines in three dimensions following 14 days of home-cage abstinence from heroin self-administration. We found that abstinence significantly increased spine head diameter (dH) and shifted the entire head-diameter distribution without altering overall spine density. Using an unsupervised model-based clustering to avoid arbitrary morphometric thresholds, we identified three distinct spine populations corresponding to classical thin, stubby, and mushroom categories. We found that abstinence reduced the density of thin-like spines and increased the density of mushroom-like spines. Overall, these findings identify the structural potentiation of excitatory inputs onto PL→PVT projection neurons as a fundamental component of the enduring circuit plasticity that sustains heroin seeking.

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BibTeX
@article{nash2026abstinence,
  title = {{Abstinence from heroin self-administration increases dendritic spine head diameter and the proportion of mushroom spines in rat prelimbic cortical neurons projecting to the paraventricular thalamus}},
  author = {Maya A. Nash and Giuseppe Giannotti},
  journal = {Brain Structure \& Function},
  year = {2026},
  month = nov,
  doi = {10.1007/s00429-026-03217-2},
  url = {https://doi.org/10.1007/s00429-026-03217-2},
  note = {CC BY-NC-ND 4.0},
}
RIS
TY  - JOUR
TI  - Abstinence from heroin self-administration increases dendritic spine head diameter and the proportion of mushroom spines in rat prelimbic cortical neurons projecting to the paraventricular thalamus
AU  - Maya A. Nash
AU  - Giuseppe Giannotti
PY  - 2026
DA  - 2026/11/05
JO  - Brain Structure & Function
DO  - 10.1007/s00429-026-03217-2
UR  - https://doi.org/10.1007/s00429-026-03217-2
AB  - Relapse to opioid use remains the principal obstacle to recovery, often driven by enduring neuroadaptations that sustain vulnerability across abstinence. We have previously shown that the projection from the rat prelimbic cortex (PL) to the paraventricular thalamus (PVT) is functionally potentiated following abstinence from heroin self-administration and is necessary for cued heroin seeking, yet whether this pathway undergoes structural remodeling remains unknown. Using an intersectional viral strategy to selectively label PL neurons projecting to the PVT in rats, we reconstructed their apical tuft dendritic spines in three dimensions following 14 days of home-cage abstinence from heroin self-administration. We found that abstinence significantly increased spine head diameter (dH) and shifted the entire head-diameter distribution without altering overall spine density. Using an unsupervised model-based clustering to avoid arbitrary morphometric thresholds, we identified three distinct spine populations corresponding to classical thin, stubby, and mushroom categories. We found that abstinence reduced the density of thin-like spines and increased the density of mushroom-like spines. Overall, these findings identify the structural potentiation of excitatory inputs onto PL→PVT projection neurons as a fundamental component of the enduring circuit plasticity that sustains heroin seeking.
SN  - 1863-2653
SN  - 1863-2661
ER  -