Hippocampal parvalbumin and perineuronal nets: Possible involvement in anxiety‐like behavior in rats

Abstract The excitatory‐inhibitory imbalance has been considered an important mechanism underlying stress‐related psychiatric disorders. In the present study, rats were exposed to 6 days of inescapable foot shock (IFS) to induce stress. The open field test and elevated plus maze test showed that IFS‐exposed rats exhibited increased anxiety‐like behavior. Immunofluorescence showed that IFS rats had a decreased density of GAD67‐immunoreactive interneurons in the dorsal hippocampal CA1 region, while no significant change in the density of CaMKIIα‐immunoreactive glutamatergic neurons was seen. We investigated the expression of different interneuron subtype markers, including parvalbumin (PV), somatostatin (SST), and calretinin (CR), and noted a marked decline in the density of PV‐immunoreactive interneurons in the dorsal CA1 region of IFS rats. The perineuronal net (PNN) is a specialized extracellular matrix structure primarily around PV interneurons. We used Wisteria floribunda agglutinin lectin to label the PNNs and observed that IFS rats had an increased proportion of PNN‐coated PV‐positive interneurons in CA1. The number of PSD95‐positive excitatory synaptic puncta on the soma of PNN‐free PV‐positive interneurons was significantly higher than that of PNN‐coated PV‐positive interneurons. Our findings suggest that the effect of IFS on the hippocampal GABAergic interneurons could be cell‐type‐specific. Loss of PV phenotype in the dorsal hippocampal CA1 region may contribute to anxiety in rats. The dysregulated PV‐PNN relationship in CA1 after traumatic stress exposure might represent one of the neurobiological correlates of the observed anxiety‐like behavior.