Accumbal Histamine Signaling Engages Discrete Interneuron Microcircuits

Area of Science:

• Neuroscience
• Cellular and Molecular Neuroscience
• Neuropharmacology

Background:

• Central histamine (HA) signaling impacts brain circuits, including the nucleus accumbens (NAc), a key area for reward behavior.
• The NAc contains diverse HA receptors that influence neuronal plasticity, but HA's role in NAc interneuron microcircuits is unclear.

Purpose of the Study:

• To investigate how HA modulates microcircuit activity within the NAc shell.
• To determine HA's influence on parvalbumin-expressing fast-spiking interneurons (PV-INs) and tonically active cholinergic interneurons (CINs).

Main Methods:

• Electrophysiology, pharmacology, voltammetry, and optogenetics were used in male transgenic reporter mice.
• Focused on microcircuit motifs controlled by PV-INs and CINs in the NAc shell.

Main Results:

• HA enhanced CIN output via H2 receptors (H2R) and Ca2+-activated K+ channels, with minor H1R and H3R contributions.
• Presynaptic H3Rs reduced feedforward input to PV-INs through AC-cAMP-PKA signaling, inducing long-term depression at specific synapses.
• These actions altered NAc microcircuits, reducing feedforward inhibition and increasing dopamine release.

Conclusions:

• HA differentially targets H1R, H2R, and H3Rs in the NAc shell.
• These targets engage specific mechanisms to bidirectionally regulate PV-IN and CIN activity.
• Findings advance understanding of HA signaling and its modulatory role in the brain.