Transcriptomic profile of the subiculum-projecting VIP GABAergic neurons in the mouse CA1 hippocampus

Brain Struct Funct. 2019 Jul;224(6):2269-2280. doi: 10.1007/s00429-019-01883-z. Epub 2019 May 16.

Abstract

In cortical circuits, the vasoactive intestinal peptide (VIP+)-expressing GABAergic cells represent a heterogeneous but unique group of interneurons that is mainly specialized in network disinhibition. While the physiological properties and connectivity patterns have been elucidated in several types of VIP+ interneurons, little is known about the cell type-specific molecular repertoires important for selective targeting of VIP+ cell types and understanding their functions. Using patch-sequencing approach, we analyzed the transcriptomic profile of anatomically identified subiculum-projecting VIP+ GABAergic neurons that reside in the mouse hippocampal CA1 area, express muscarinic receptor 2 and coordinate the hippocampo-subicular interactions via selective innervation of interneurons in the CA1 area and of interneurons and pyramidal cells in subiculum. We explored the VIP+ cell gene expression within major gene families including ion channels, neurotransmitter receptors, neuromodulators, cell adhesion and myelination molecules. Among others, a large variety of genes involved in neuromodulatory signaling, including acetylcholine (Chrna4), norepinephrin (Adrb1), dopamine (Drd1), serotonin (Htr1d), cannabinoid (Cnr1), opioid (Oprd1, Oprl1) and neuropeptide Y (Npy1r) receptors was detected in these cells. Many genes that were enriched in other local VIP+ cell types, including the interneuron-selective interneurons and the cholecystokinin-coexpressing basket cells, were detected in VIP+ subiculum-projecting cells. In addition, the neuronatin (Nnat) and the Purkinje Cell Protein 4 (Pcp4) genes, which were detected previously in long-range projecting GABAergic neurons, were also common for the subiculum-projecting VIP+ cells. The expression of some genes was validated at the protein level, with proenkephalin being identified as an additional molecular marker of this VIP+ cell type. Together, our data indicate that the VIP+ subiculum-projecting cells share molecular identity with other VIP+ and long-range projecting GABAergic neurons, which can be important for specific function of these cells associated with their local and distant projection patterns.

Keywords: Inhibition; Patch-sequencing; Subiculum-projecting GABAergic cell; Vasoactive intestinal peptide.

MeSH terms

  • Acetylcholine / metabolism
  • Animals
  • Cholecystokinin / metabolism
  • GABAergic Neurons / metabolism*
  • Hippocampus / metabolism*
  • Interneurons / metabolism*
  • Mice, Transgenic
  • Nerve Tissue Proteins / metabolism
  • Presynaptic Terminals / metabolism
  • Pyramidal Cells / metabolism*
  • Receptors, Muscarinic / metabolism

Substances

  • Nerve Tissue Proteins
  • Receptors, Muscarinic
  • Cholecystokinin
  • Acetylcholine