Regulation of Kainate Receptor Subunit mRNA by Stress and Corticosteroids in the Rat Hippocampus

Kainate receptors are a class of ionotropic glutamate receptors that have a role in the modulation of glutamate release and synaptic plasticity in the hippocampal formation. Previous studies have implicated corticosteroids in the regulation of these receptors and recent clinical work has shown that polymorphisms in kainate receptor subunit genes are associated with susceptibility to major depression and response to anti-depressant treatment. In the present study we sought to examine the effects of chronic stress and corticosteroid treatments upon the expression of the mRNA of kainate receptor subunits GluR5-7 and KA1-2. Our results show that, after 7 days, adrenalectomy results in increased expression of hippocampal KA1, GluR6 and GluR7 mRNAs, an effect which is reversed by treatment with corticosterone in the case of KA1 and GluR7 and by aldosterone treatment in the case of GluR6. 21 days of chronic restraint stress (CRS) elevated the expression of the KA1 subunit, but had no effect on the expression of the other subunits. Similarly, 21 days of treatment with a moderate dose of corticosterone also increased KA1 mRNA in the dentate gyrus, whereas a high corticosterone dose has no effect. Our results suggest an interaction between hippocampal kainate receptor composition and the hypothalamic-pituitary-adrenal (HPA) axis and show a selective chronic stress induced modulation of the KA1 subunit in the dentate gyrus and CA3 that has implications for stress-induced adaptive structural plasticity

Vocal Handedness: The Emergence of Lateralization at Fledging

Adult waterslager canaries produce the majority of their song under the control of the left hemisphere / left syringeal half. Unilateral section of the left treacheosyringeal nerve results in near complete loss of song while right denervation affects only a subset of call elements. This strong asymmetry for the production of a learned vocalization is reminiscent of the left hemisphere control for language in humans and provides a potentially powerful animal model to study lateralized behaviors in the vertebrate brain. ! Earlier work on another songbird, the European chaffinch, Friungilla crebes, suggested that the onset of lateralized vocalizations occured before song learning took place, but did not provide information about when and where this functional asymmetry first occurred. This “when†and “how†became the focus of my thesis. ! In chapter 2, I describe the vocal ontogeny of begging calls in the canary, Serinus canaria. I describe the major call types, focusing primarily on two calls I named type A and type B. I show that the two calls are not interchangeable and are produced in different contexts as well as in different positions in the begging bout. Moreover, I show that B calls first appear as modifications of A calls and are mechanically produced differently by the bird. Using call structure analysis, I suggest that B calls may provide location information to parents, a suggestion that is supported by my finding that the emergence of B calls coincides with the time when young canaries leave the nest, which is referred to as ‘fledging.’ ! In chapter 3, I performed unilateral denervations across begging call ontogeny and found that late, but not early begging calls are asymmetrically produced. I further show that this onset of asymmetric contributions to the begging call by the syrinx emerges suddenly across one day -the day B calls appear and birds fledge. Call analysis revealed that both A and B calls are affected and thus, fascinatingly, A calls, which are little affected by syringeal denervation before P15, fall asymmetrically under the influence of the left syringeal half at P16. Track tracing experiments reveal that the descending motor pathway for food begging in canaries projects ipsilaterally, suggesting that the left / right differences in vocal control observed at the level of the syrinx, mirror left / right differences in control that occur at higher brain areas. ! In chapter 4, I describe that food deprivation can shift the timing of fledging earlier. Furthermore, fledging earlier was accompanied by B call production and the onset of lateralized begging calls. The correlative emergence of these phenomena in stressed and unstressed canaries is striking and I propose that B calls serve a new communicative need that arises with leaving the nest -namely, locatability. The emergence of vocal lateralization when the bird leaves the nest, regardless of age at which it occurs, is also curious and I posit that if lateralization of function is a way of compartmentalizing the complex world, then perhaps laterality arises when this world is first met

Representative photomicrographs showing KA2 mRNA signal on the right and GluR5 mRNA on the left.

<p>We did not observe changes in expression of either of these transcripts.</p

ROD of KA1 mRNA in the dentate gyrus (A) and CA3 (B) after 21 day treatment with either vehicle, 25 µg/ml or 400 µg/ml corticosterone in drinking water.

<p>*-significantly different from vehicle treated animals (p<0.05, n = 8).</p

ROD of GluR6 mRNA in the dentate gyrus (A) CA3 (B) and CA1 (C) after adrenalectomy and treatment with vehicle (ADX), aldosterone (ADX+Aldo) RU28,362 (ADX+RU362) or corticosterone (ADX+CORT).

<p>(D) A representative autoradiogram of GluR6 mRNA. *-significantly different from sham and ADX+CORT (p<0.05, n = 8).</p

ROD of KA1 mRNA in the dentate gyrus (A) and CA3 (B) after adrenalectomy and treatment with vehicle (ADX), aldosterone (ADX+Aldo) RU28,362 (ADX+RU362) or corticosterone (ADX+CORT).

<p>(C) A representative autoradiogram of KA1 mRNA. *-significantly different from sham and ADX+Cort (p<0.05, n = 8). **-significantly different from ADX (p<0.05, n = 8).</p

ROD of KA1 mRNA in the dentate gyrus (A) and CA3 (B) after CRS.

<p>*-significantly different from unstressed controls (p<0.05, n = 8).</p