Paraventricular Thalamus Projection Neurons Integrate Cortical and Hypothalamic Signals for Cue-Reward Processing

Neuron. 2019 Aug 7;103(3):423-431.e4. doi: 10.1016/j.neuron.2019.05.018. Epub 2019 Jun 10.

Abstract

The paraventricular thalamus (PVT) is an interface for brain reward circuits, with input signals arising from structures, such as prefrontal cortex and hypothalamus, that are broadcast to downstream limbic targets. However, the precise synaptic connectivity, activity, and function of PVT circuitry for reward processing are unclear. Here, using in vivo two-photon calcium imaging, we find that PVT neurons projecting to the nucleus accumbens (PVT-NAc) develop inhibitory responses to reward-predictive cues coding for both cue-reward associative information and behavior. The multiplexed activity in PVT-NAc neurons is directed by opposing activity patterns in prefrontal and lateral hypothalamic afferent axons. Further, we find that prefrontal cue encoding may maintain accurate cue-reward processing, as optogenetic disruption of this encoding induced long-lasting effects on downstream PVT-NAc cue responses and behavioral cue discrimination. Together, these data reveal that PVT-NAc neurons act as an interface for reward processing by integrating relevant inputs to accurately inform reward-seeking behavior.

Keywords: behavioral optogenetics; drug addiction; feeding; lateral hypothalamus; learning; memory; midline thalamus; multiphoton calcium imaging; prelimbic cortex; sucrose seeking.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Association Learning / physiology*
  • Conditioning, Classical
  • Craving / physiology
  • Cues
  • Glutamic Acid / physiology
  • Hypothalamic Area, Lateral / cytology
  • Hypothalamic Area, Lateral / physiology*
  • Mice
  • Midline Thalamic Nuclei / cytology
  • Midline Thalamic Nuclei / physiology*
  • Neural Pathways / physiology
  • Neurons / physiology*
  • Optogenetics
  • Patch-Clamp Techniques
  • Prefrontal Cortex / cytology
  • Prefrontal Cortex / physiology*
  • Reward
  • gamma-Aminobutyric Acid / physiology

Substances

  • Glutamic Acid
  • gamma-Aminobutyric Acid