Ventral midline thalamus lesion prevents persistence of new (learning-triggered) hippocampal spines, delayed neocortical spinogenesis, and spatial memory durability

Brain Struct Funct. 2019 May;224(4):1659-1676. doi: 10.1007/s00429-019-01865-1. Epub 2019 Mar 29.


The ventral midline thalamus contributes to hippocampo-cortical interactions supporting systems-level consolidation of memories. Recent hippocampus-dependent memories rely on hippocampal connectivity remodeling. Remote memories are underpinned by neocortical connectivity remodeling. After a ventral midline thalamus lesion, recent spatial memories are formed normally but do not last. Why these memories do not endure after the lesion is unknown. We hypothesized that a lesion could interfere with hippocampal and/or neocortical connectivity remodeling. To test this hypothesis, in a first experiment male rats were subjected to lesion of the reuniens and rhomboid (ReRh) nuclei, trained in a water maze, and tested in a probe trial 5 or 25 days post-acquisition. Dendritic spines were counted in the dorsal hippocampus and medial prefrontal cortex. Spatial learning resulted in a significant increase of mushroom spines in region CA1. This modification persisted between 5 and 25 days post-acquisition in Sham rats, not in rats with ReRh lesion. Furthermore, 25 days after acquisition, the number of mushroom spines in the anterior cingulate cortex (ACC) had undergone a dramatic increase in Sham rats; ReRh lesion prevented this gain. In a second experiment, the increase of c-Fos expression in CA1 accompanying memory retrieval was not affected by the lesion, be it for recent or remote memory. However, in the ACC, the lesion had reduced the retrieval-triggered c-Fos expression observed 25 days post-acquisition. These observations suggest that a ReRh lesion might disrupt spatial remote memory formation by preventing persistence of early remodeled hippocampal connectivity, and spinogenesis in the ACC.

Keywords: Anterior cingulate cortex; Dendritic spines; Golgi staining; Hippocampus; Medial prefrontal cortex; Rat; Spatial memory; Systems-level consolidation; c-Fos imaging.

MeSH terms

  • Animals
  • CA1 Region, Hippocampal / physiology*
  • Dendritic Spines / physiology*
  • Gyrus Cinguli / physiology
  • Male
  • Maze Learning / physiology
  • Memory, Long-Term / physiology
  • Midline Thalamic Nuclei / physiology*
  • Neuronal Plasticity*
  • Prefrontal Cortex / physiology*
  • Rats, Long-Evans
  • Spatial Memory / physiology*