Ventral Subiculum Stimulation Promotes Persistent Hyperactivity of Dopamine Neurons and Facilitates Behavioral Effects of Cocaine

Cell Rep. 2015 Dec 15;13(10):2287-96. doi: 10.1016/j.celrep.2015.10.076. Epub 2015 Nov 25.

Abstract

The ventral subiculum (vSUB) plays a key role in addiction, and identifying the neuronal circuits and synaptic mechanisms by which vSUB alters the excitability of dopamine neurons is a necessary step to understand the motor changes induced by cocaine. Here, we report that high-frequency stimulation of the vSUB (HFSvSUB) over-activates ventral tegmental area (VTA) dopamine neurons in vivo and triggers long-lasting modifications of synaptic transmission measured ex vivo. This potentiation is caused by NMDA-dependent plastic changes occurring in the bed nucleus of the stria terminalis (BNST). Finally, we report that the modification of the BNST-VTA neural circuits induced by HFSvSUB potentiates locomotor activity induced by a sub-threshold dose of cocaine. Our findings unravel a neuronal circuit encoding behavioral effects of cocaine in rats and highlight the importance of adaptive modifications in the BNST, a structure that influences motivated behavior as well as maladaptive behaviors associated with addiction.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cocaine / pharmacology*
  • Cocaine-Related Disorders / physiopathology
  • Disease Models, Animal
  • Dopamine Uptake Inhibitors / pharmacology*
  • Dopaminergic Neurons / drug effects*
  • Dopaminergic Neurons / physiology
  • Electric Stimulation
  • Hippocampus / drug effects*
  • Hippocampus / physiology
  • Immunohistochemistry
  • Motor Activity / drug effects
  • Motor Activity / physiology
  • Neural Pathways / drug effects
  • Neural Pathways / physiology
  • Patch-Clamp Techniques
  • Rats
  • Rats, Sprague-Dawley
  • Synaptic Transmission / drug effects*
  • Synaptic Transmission / physiology

Substances

  • Dopamine Uptake Inhibitors
  • Cocaine