HIV-1 Tat alters neuronal intrinsic excitability

Abstract

ObjectiveIn HIV+ individuals, the virus enters the central nervous system and invades innate immune cells, producing important changes that result in neurological deficits. We aimed to determine whether HIV plays a direct role in neuronal excitability. Of the HIV peptides, Tat is secreted and acts in other cells. In order to examine whether the HIV Tat can modify neuronal excitability, we exposed primary murine hippocampal neurons to that peptide, and tested its effects on the intrinsic membrane properties, 4 and 24 h after exposure.ResultsThe exposure of hippocampal pyramidal neurons to Tat for 4 h did not alter intrinsic membrane properties. However, we found a strong increase in intrinsic excitability, characterized by increase of the slope (Gain) of the input–output function, in cells treated with Tat for 24 h. Nevertheless, Tat treatment for 24 h did not alter the resting membrane potential, input resistance, rheobase and action potential threshold. Thus, neuronal adaptability to Tat exposure for 24 h is not applicable to basic neuronal properties. A restricted but significant effect on coupling the inputs to the outputs may have implications to our knowledge of Tat biophysical firing capability, and its involvement in neuronal hyperexcitability in neuroHIV.

[3H]Dopamine Uptake through the Dopamine and Norepinephrine Transporters is Decreased in the Prefrontal Cortex of Transgenic Mice Expressing HIV-1 Transactivator of Transcription Protein

“…Together, these observations suggest that decreased action potential firing of prelimbic cortex pyramidal neurons in iTat-tg mice is not directly related to Tat effects on DA transport. HIV-1 Tat may, however, affect action potential generation through mechanisms independent of DA uptake, with a variety of bidirectional effects reported by previous studies (Krogh et al, 2014;Ngwainmbi et al, 2014;Francesconi et al, 2018;Mohseni Ahooyi et al, 2018).…”

HIV-1 Tat and Morphine Differentially Disrupt Pyramidal Cell Structure and Function and Spatial Learning in Hippocampal Area CA1: Continuous versus Interrupted Morphine Exposure

“…Tat additionally reduced intrinsic excitability, which is also seen with prolonged Tat applications ( Francesconi et al, 2018 ). Analysis of contrasts assessing possible morphine and Tat interactions revealed that changes in membrane potential and rheobase were largely driven by Tat.…”

“…Analysis of contrasts assessing possible morphine and Tat interactions revealed that changes in membrane potential and rheobase were largely driven by Tat. Interestingly, more protracted exposure to Tat does not alter intrinsic membrane properties despite altered excitability ( Francesconi et al, 2018 ), suggesting the network effects of Tat precede its direct effects on CA1 pyramidal cells. However, based on morphologic measures and past studies, Tat is likely affecting both the pyramidal cells and the interneuron network ( Fitting et al, 2013 ; Marks et al, 2016 ; Francesconi et al, 2018 ).…”