Neurochemical Research

, Volume 44, Issue 1, pp 234–246 | Cite as

Scaling Synapses in the Presence of HIV

  • Matthew V. Green
  • Jonathan D. Raybuck
  • Xinwen Zhang
  • Mariah M. Wu
  • Stanley A. ThayerEmail author
Original Paper


A defining feature of HIV-associated neurocognitive disorder (HAND) is the loss of excitatory synaptic connections. Synaptic changes that occur during exposure to HIV appear to result, in part, from a homeostatic scaling response. Here we discuss the mechanisms of these changes from the perspective that they might be part of a coping mechanism that reduces synapses to prevent excitotoxicity. In transgenic animals expressing the HIV proteins Tat or gp120, the loss of synaptic markers precedes changes in neuronal number. In vitro studies have shown that HIV-induced synapse loss and cell death are mediated by distinct mechanisms. Both in vitro and animal studies suggest that HIV-induced synaptic scaling engages new mechanisms that suppress network connectivity and that these processes might be amenable to therapeutic intervention. Indeed, pharmacological reversal of synapse loss induced by HIV Tat restores cognitive function. In summary, studies indicate that there are temporal, mechanistic and pharmacological features of HIV-induced synapse loss that are consistent with homeostatic plasticity. The increasingly well delineated signaling mechanisms that regulate synaptic scaling may reveal pharmacological targets suitable for normalizing synaptic function in chronic neuroinflammatory states such as HAND.


HIV-1 Homeostatic plasticity NMDA receptor Synaptic scaling HIV-associated neurocognitive disorder 



This work was supported by the National Institute on Drug Abuse—National Institutes of Health Grant DA07304.

Compliance with Ethical Standards

Conflict of interest

The authors declare they have no competing interests.


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Authors and Affiliations

  1. 1.Department of PharmacologyUniversity of Minnesota Medical SchoolMinneapolisUSA

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