[Abstract Title]. - Society for Neuroscience

Title: Altered wiring of emotional-somatomotor, but not limbic-autonomic, circuits in rat models
of depression
Authors: *I. A. KERMAN, S. M. CLINTON, P. R. BURGHARDT, N. MUZAMHINDO, N.
VACHHANI, C. SHABRANG, J. BEALS, H. AKIL, S. J. WATSON;
Molec & Behav Neurosci Inst., Univ. Michigan, Ann Arbor, MI
Abstract: In addition to cognitive and affective disturbances, major depression is characterized
by physical symptoms, including dysregulation of motor control and autonomic dysfunction. We
hypothesized that such functional alterations may be due to differential organization of brain
circuits that regulate these functions. To test this hypothesis, we used a virally-mediated transsynaptic
tract-tracing approach to delineate emotional-somatomotor, limbic-autonomic and
somatomotor-sympathetic circuits in the rat using distinct pseudorabies virus (PRV)
recombinants. Experiments were carried out in two models of depression: the Wistar-Kyoto
(WKY) rat (compared to the Sprague-Dawley (SD) rat) and the Low Responder (LR) rat
(compared to the High Responder (HR) rat). Behavioral studies confirmed the expression of
depressive-like phenotypes in WKY and LR rats. Specifically, WKY rats exhibited significantly
more immobility (91.3 ± 2.7% vs. 12.6 ± 5.5%; p < 0.01), and significantly less swimming (8.7 ±
2.7% vs. 70.8 ± 6.6%; p < 0.01) and climbing (0% vs. 16.6 ± 4.7%; p < 0.01) compared to SD
controls on the forced swim test (FST). Likewise, LR rats were significantly more immobile
(68.5 ± 9.3% vs. 28.6 ± 7.5%; p < 0.01) and swam significantly less (24.0 ± 4.8% vs. 52.5 ±
5.3%; p < 0.01) on the FST compared to their HR counterparts. Virally-mediated transsynaptic
tract-tracing studies revealed large differences in the numbers of neurons with poly-synaptic
projections to skeletal muscle, but not to the adrenal gland, in the paraventricular nucleus of the
hypothalamus (PVN) in both depression models compared to their respective controls.
Accordingly, SD rats contained approximately three times as many neurons with poly-synaptic
projections to skeletal muscle compared to WKY rats, while similar differences were detected
between HR and LR rats. There were no WKY/SD or LR/HR differences in the numbers of
neurons with poly-synaptic projections to the adrenal gland, or in the numbers of neurons with
collateralized poly-synaptic projections to both muscle and adrenal gland. Likewise, there were
no WKY/SD or LR/HR differences in the numbers of labeled gastrocnemius motoneurons,
suggesting that observed differences in the PVN were not due to disparate PRV entry into firstorder
neurons. Overall, these data suggest differential wiring of emotional-somatomotor circuits
in two different genetic rat models of depression, which may underlie their distinct behavioral
phenotypes.
Disclosures: I.A. Kerman , None; S.M. Clinton, None; P.R. Burghardt, None; N.
Muzamhindo, None; N. Vachhani, None; C. Shabrang, None; J. Beals, None; H. Akil,
None; S.J. Watson, None.
Poster
283. Stress-Regulated Pathways II