Hyperexcitable Parvalbumin Interneurons Render Hippocampal Circuitry Vulnerable to Amyloid Beta

Sara Hijazi, Tim S. Heistek, Rolinka van der Loo, Huibert D. Mansvelder, August B. Smit, Ronald E. van Kesteren*

*Corresponding author for this work

Research output: Contribution to JournalArticleAcademicpeer-review


Parvalbumin (PV) interneuron dysfunction is associated with various brain disorders, including Alzheimer disease (AD). Here, we asked whether early PV neuron hyperexcitability primes the hippocampus for amyloid beta-induced functional impairment. We show that prolonged chemogenetic activation of PV neurons induces long-term hyperexcitability of these cells, disrupts synaptic transmission, and causes spatial memory deficits on the short-term. On the long-term, pyramidal cells also become hyperexcitable, and synaptic transmission and spatial memory are restored. However, under these conditions of increased excitability of both PV and pyramidal cells, a single low-dose injection of amyloid beta directly into the hippocampus significantly impairs PV neuron function, increases pyramidal neuron excitability, and reduces synaptic transmission, resulting in significant spatial memory deficits. Taken together, our data show that an initial hyperexcitable state of PV neurons renders hippocampal function vulnerable to amyloid beta and may contribute to an increased risk for developing AD.

Original languageEnglish
Article number101271
Pages (from-to)1-25
Number of pages25
Issue number7
Publication statusPublished - 24 Jul 2020


  • Cellular Neuroscience
  • Neuroscience
  • Systems Neuroscience


Dive into the research topics of 'Hyperexcitable Parvalbumin Interneurons Render Hippocampal Circuitry Vulnerable to Amyloid Beta'. Together they form a unique fingerprint.

Cite this