Transsynaptic trophic effects of steroid hormones in an avian model of adult brain plasticity

Abstract

The avian song control system provides an excellent model for studying transsynaptic trophic effects of steroid sex hormones. Seasonal changes in systemic testosterone (T) and its metabolites regulate plasticity of this system. Steroids interact with the neurotrophin brain-derived neurotrophic factor (BDNF) to influence cellular processes of plasticity in nucleus HVC of adult birds, including the addition of newborn neurons. This interaction may also occur transsynpatically; T increases the synthesis of BDNF in HVC, and BDNF protein is then released by HVC neurons on to postsynaptic cells in nucleus RA where it has trophic effects on activity and morphology. Androgen action on RA neurons increases their activity and this has a retrograde trophic effect on the addition of new neurons to HVC. The functional linkage of sex steroids to BDNF may be of adaptive value in regulating the trophic effects of the neurotrophin and coordinating circuit function in reproductively relevant contexts.

Keywords: BDNF; Bird; Estrogen; Neurogenesis; Neurotrophin; Plasticity; Season; Songbird; Steroid; Testosterone.

Figure 1

Simplified schematic sagittal view of the avian song control system showing the distribution of steroid receptors. Black arrows connect nuclei in the main descending motor circuit, and gray arrows connect nuclei in the anterior forebrain circuit. Abbreviations: AM- nucleus ambiguus; DLM, Dorsolateral nucleus of the medial thalamus; lMAN, lateral portion of the magnocellular nucleus of the anterior nidopallium; nXIIts, the tracheosyringeal portion of the hypoglossal nucleus; RA, the robust nucleus of the arcopallium; RAm – nucleus retroambigualis; syrinx, vocal production organ; V, lateral ventricle; X, area X of the medial striatum.

Figure 2

Seasonal changes in androgen receptor expression in HVC of White-crowned Sparrows. Bottom panel: AR mRNA is expressed at higher levels in HVC of breeding birds [adapted from 50]. Scale-bar = 0.5 mm. Top panel: The density and immunostaining intensity of cells positive for AR-like protein are greater in HVC of breeding sparrows. Note that nonbreeding birds have fainter staining within cell nuclei [adapted from 48]. Scale bar = 20 μm.

Figure 3

Dark-field photomicrographs of in situ hybridization showing seasonal change in BDNF mRNA expression in HVC of White-crowned Sparrows. BDNF is expressed at higher levels in HVC of breeding birds. Arrows delineate the ventral border of HVC. Scale bar, 300 μm.

Figure 4

Postsynaptic activity influences the addition of new RA-projecting neurons to HVC. Spontaneous activity of neurons in RA was decreased by unilateral infusions of muscimol [2.8 mg/ml 27] or increased by infusion of KCl (100 mM, n = 5 birds; Larson, Wang, and Brenowitz, unpublished observation ). Inhibiting activity decreased neuronal addition and increasing activity increased neurogenesis in HVC.

Figure 5

A summary of the main interactions between photoperiod, hormones, neurotrophins, brain, and behavior that characterize seasonal plasticity of the song system. See text for explanation. (Figure prepared by T. Larson.)