Reduced intrinsic excitability of CA1 pyramidal neurons in human immunodeficiency virus (HIV) transgenic rats

Irina V. Sokolova, Attila Szucs, Pietro Paolo Sanna

Research output: Contribution to journalArticle

Abstract

The hippocampus is involved in key neuronal circuits that underlie cognition, memory, and anxiety, and it is increasingly recognized as a vulnerable structure that contributes to the pathogenesis of HIV-associated neurocognitive disorder (HAND). However, the mechanisms responsible for hippocampal dysfunction in neuroHIV remain unknown. The present study used HIV transgenic (Tg) rats and patch-clamp electrophysiological techniques to study the effects of the chronic low-level expression of HIV proteins on hippocampal CA1 pyramidal neurons. The dorsal and ventral areas of the hippocampus are involved in different neurocircuits and thus were evaluated separately. We found a significant decrease in the intrinsic excitability of CA1 neurons in the dorsal hippocampus in HIV Tg rats by comparing neuronal spiking induced by current step injections and by dynamic clamp to simulate neuronal spiking activity. The decrease in excitability in the dorsal hippocampus was accompanied by a higher rate of excitatory postsynaptic currents (EPSCs), whereas CA1 pyramidal neurons in the ventral hippocampus in HIV Tg rats had higher EPSC amplitudes. We also observed a reduction of hyperpolarization-activated nonspecific cationic current (Ih) in both the dorsal and ventral hippocampus. Neurotoxic HIV proteins have been shown to increase neuronal excitation. The lower excitability of CA1 pyramidal neurons that was observed herein may represent maladaptive homeostatic plasticity that seeks to stabilize baseline neuronal firing activity but may disrupt neural network function and contribute to HIV-associated neuropsychological disorders, such as HAND and depression.

Original languageEnglish
Article number146431
JournalBrain research
Volume1724
DOIs
Publication statusPublished - Dec 1 2019

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Keywords

  • Dementia
  • Neurocognitive disorders
  • Neuronal excitability
  • Synaptodendritic
  • Transgenic
  • neuroHIV

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology

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