Postnatal Fluoxetine Treatment Alters Perineuronal Net Formation and Maintenance in the Hippocampus

Area of Science:

• Neuroscience
• Developmental Biology
• Neuropharmacology

Background:

• Postnatal fluoxetine (PNFlx) exposure during critical developmental periods may disrupt limbic circuit formation.
• Perineuronal nets (PNNs) are extracellular matrix structures crucial for stabilizing neural circuits and marking the end of critical plasticity periods.

Purpose of the Study:

• To investigate the impact of PNFlx treatment on PNN formation and maintenance in the developing rat hippocampus.
• To assess associated changes in neuronal populations, dendritic complexity, and neuronal activation.

Main Methods:

• Sprague Dawley rat pups were treated with PNFlx during specific postnatal windows.
• Immunohistochemistry was used to quantify PNNs and specific interneuron populations (PV, CalR, Reelin, SST).
• GABA-A receptor subunit composition, dendritic complexity, and c-Fos expression were analyzed in adult animals.

Main Results:

• PNFlx treatment significantly reduced PNN numbers, particularly around parvalbumin (PV) interneurons, in the hippocampus at postnatal day 21.
• This PNN reduction persisted in adulthood in the CA1 subfield, though PV-PNN colocalization normalized.
• Adult PNFlx-treated rats showed increased somatostatin (SST)-positive interneurons, altered GABA-A receptor composition, increased dendritic complexity, and heightened neuronal activation (c-Fos).

Conclusions:

• PNFlx exposure disrupts PNN formation in the developing hippocampus, suggesting a potential mechanism for long-term mood-related behavioral disruptions.
• Altered PNNs may contribute to changes in excitation-inhibition (E/I) balance within the hippocampus.
• These findings highlight the sensitivity of early brain development to serotonergic modulation and its lasting impact on neural circuit stability.