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Front. Behav. Neurosci. | doi: 10.3389/fnbeh.2018.00285

SYNAPTIC CONNECTIVITY IN MEDIUM SPINY NEURONS OF THE NUCLEUS ACCUMBENS: A SEX-DEPENDENT MECHANISM UNDERLYING APATHY IN THE HIV-1 TRANSGENIC RAT

 Kristen A. McLaurin1,  Anna K. Cook1, Hailong Li1,  Alexis F. League1, Charles F. Mactutus1 and  Rosemarie M. Booze1*
  • 1University of South Carolina, United States

Frontal-subcortical circuit dysfunction is commonly associated with apathy, a neuropsychiatric sequelae of human immunodeficiency virus type-1 (HIV-1). Behavioral and neurochemical indices of activity in the nucleus accumbens (NAc), a key brain region involved in frontal-subcortical circuitry, are influenced by the factor of biological sex. Despite evidence of sex differences in HIV-1, the effect of biological sex on medium spiny neurons (MSNs), which are central integrators of frontal-subcortical input, has not been systematically evaluated. In the present study, a DiOlistic labeling technique was used to investigate the role of long-term HIV-1 viral protein exposure, the factor of biological sex, and their possible interaction, on synaptic dysfunction in MSNs of the NAc in the HIV-1 transgenic (Tg) rat. HIV-1 Tg rats, independent of biological sex, displayed profound alterations in synaptic connectivity, evidenced by a prominent shift in the distribution of dendritic spines. Female HIV-1 Tg rats, but not male HIV-1 Tg rats, exhibited alterations in dendritic branching and neuronal arbor complexity relative to control animals, supporting an alteration in glutamate neurotransmission. Morphologically, HIV-1 Tg male, but not female HIV-1 Tg rats, displayed a population shift towards decreased dendritic spine volume, suggesting decreased synaptic area, relative to control animals. Synaptic dysfunction accurately identified presence of the HIV-1 transgene, dependent upon biological sex, with at least 80% accuracy (i.e., Male: 80%; Female: 90%). Collectively, these results support a primary alteration in circuit connectivity, the mechanism of which is dependent upon biological sex. Understanding the effect of biological sex on the underlying neural mechanism for HIV-1 associated apathy is vital for the development of sex-based therapeutics and cure strategies.

Keywords: HIV-1 transgenic rat, Biological sex, Medium Spiny Neuron (MSN), Dopamine, Apathy

Received: 05 Sep 2018; Accepted: 05 Nov 2018.

Edited by:

Etsuro Ito, Waseda University, Japan

Reviewed by:

Carla Cannizzaro, Università degli Studi di Palermo, Italy
Anna Brancato, Università degli Studi di Palermo, Italy
Ja Wook Koo, Korea Brain Research Institute, South Korea  

Copyright: © 2018 McLaurin, Cook, Li, League, Mactutus and Booze. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. Rosemarie M. Booze, University of South Carolina, Columbia, United States, booze@mailbox.sc.edu