Effects of ovariectomy on the inputs from the medial nucleus of the amygdala to the ventromedial nucleus of the hypothalamus in young adult rats.

During puberty, sexual hormones induce crucial changes in neural circuit organization, leading to significant sexual dimorphism in adult behaviours. The ventrolateral division of the ventromedial nucleus of the hypothalamus (VMHvl) is the major neural site controlling the receptive component of female sexual behaviour, which is dependent on ovarian hormones. The inputs to the VMHvl, originating from the medial nucleus of the amygdala (MeA), transmit essential information to trigger such behaviour. In this study, we investigated the projection pattern of the MeA to the VMHvl in ovariectomized rats at early puberty. Six-week-old Sprague-Dawley rats were ovariectomized (OVX) and, upon reaching 90 days of age, were subjected to iontophoretic injections of the neuronal anterograde tracer Phaseolus vulgaris leucoagglutinin into the MeA. Projections from the MeA to the VMHvl and to other structures included in the neural circuit responsible for female sexual behaviour were analysed in the Control and OVX groups. The results of the semi-quantitative analysis showed that peripubertal ovariectomy reduced the density of intra-amygdalar fibres. The stereological estimates, however, failed to find changes in the organization of the terminal fields of nerve fibres from the MeA to the VMHvl in the adult. The present data show that ovariectomized rats during the peripubertal phase did not undergo significant changes in MeA fibres reaching the VMHvl; however, they suggest a possible effect of ovariectomy on MeA connectivity under amygdalar subnuclei.

MEMRI detects neuronal activity and connectivity in hypothalamic neural circuit responding to leptin.

Hypothalamus plays the central role in regulating energy homeostasis. To understand the hypothalamic neurocircuit in responding to leptin, Manganese-Enhanced MRI (MEMRI) was applied. Highly elevated signal could be mapped in major nuclei of the leptin signaling pathway, including the arcuate nucleus (ARC), paraventricular nucleus (PVN), ventromedial hypothalamus (VMH) and dorsomedial hypothalamus (DMH) in fasted mice and the enhancement was reduced by leptin administration. However, whether changes in MEMRI signal reflect Ca2+ channel activity, neuronal activation or connectivity in the leptin signaling pathway are not clear. By blocking L-type Ca2+ channels, the signal enhancement in the ARC, PVN and DMH, but not VMH, was reduced. By disrupting microtubule with colchicine, signal enhancement of the secondary neural areas like DMH and PVN was delayed which is consistent with the known projection density from ARC into these regions. Finally, strong correlation between c-fos expression and MEMRI signal increase rate was observed in the ARC, VMH and DMH. Together, we provide experimental evidence that MEMRI signal could represent activity and connectivity in certain hypothalamic nuclei and hence may be used for mapping activated neuronal pathway in vivo. This understanding would facilitate the application of MEMRI for evaluation of hypothalamic dysfunction in metabolic diseases.

Endogenous VMH amylin signaling is required for full leptin signaling and protection from diet-induced obesity.

Amylin enhances arcuate (ARC) and ventromedial (VMN) hypothalamic nuclei leptin signaling and synergistically reduces food intake and body weight in selectively bred diet-induced obese (DIO) rats. Since DIO (125)I-amylin dorsomedial nucleus-dorsomedial VMN binding was reduced, we postulated that this contributed to DIO ventromedial hypothalamus (VMH) leptin resistance, and that impairing VMH (ARC + VMN) calcitonin receptor (CTR)-mediated signaling by injecting adeno-associated virus (AAV) expressing a short hairpin portion of the CTR mRNA would predispose diet-resistant (DR) rats to obesity on high-fat (45%) diet (HFD). Depleting VMH CTR by 80-90% in 4-wk-old male DR rats reduced their ARC and VMN (125)I-labeled leptin binding by 57 and 51%, respectively, and VMN leptin-induced phospho-signal transducer and activator of transcription 3-positive neurons by 59% vs. AAV control rats. After 6 wk on chow, VMH CTR-depleted DR rats ate and gained the equivalent amount of food and weight but had 18% heavier fat pads (relative to carcass weight), 144% higher leptin levels, and were insulin resistant compared with control AAV DR rats. After 6 wk more on HFD, VMH CTR-depleted DR rats ate the same amount but gained 28% more weight, had 60% more carcass fat, 254% higher leptin levels, and 132% higher insulin areas under the curve during an oral glucose tolerance test than control DR rats. Therefore, impairing endogenous VMH CTR-mediated signaling reduced leptin signaling and caused DR rats to become more obese and insulin resistant, both on chow and HFD. These results suggest that endogenous VMH amylin signaling is required for full leptin signaling and protection from HFD-induced obesity.

A probabilistic functional atlas of the VIM nucleus constructed from pre-, intra- and postoperative electrophysiological and neuroimaging data acquired during the surgical treatment of Parkinson's disease patients.

We have previously introduced a concept of a probabilistic functional atlas (PFA) to overcome limitations of the current electronic stereotactic brain atlases: anatomical nature, spatial sparseness, inconsistency and lack of population information. The PFA for the STN has already been developed. This work addresses construction of the PFA for the ventrointermediate nucleus (PFA-VIM). The PFA-VIM is constructed from pre-, intra- and postoperative electrophysiological and neuroimaging data acquired during the surgical treatment of Parkinson's disease patients. The data contain the positions of the chronically implanted electrodes and their best contacts. For each patient, the intercommissural distance, height of the thalamus and width of the third ventricle were measured. An algorithm was developed to convert these data into the PFA-VIM, and to present them on axial, coronal and sagittal planes and in 3-D. The PFA-VIM gives a spatial distribution of the best contacts, and its probability is proportional to best contact concentration in a given location. The region with the highest probability corresponds to the best target. The PFA-VIM is calculated with 0.25-mm3 resolution from 107 best contacts in two situations: with and without lateral compensation against the width of the third ventricle. For the PFA-VIM compensated laterally, the anterior, lateral and dorsal coordinates of the mean value are (in mm) 6.24, 13.83, 1.68 for the left VIM and 6.54, -13.84, 2.10 for the right VIM. The coordinates of the mean value of the highest probability region along with the highest number of the best contacts (P) are: 6.25, 14.25, 1.75, P = 16, for the left VIM, and 6.0, -14.0, 1.00, P = 18, for the right VIM. The coordinate system origin is at the posterior commissure. For the PFA-VIM not compensated laterally, the coordinates of the mean value are 6.24, 13.99, 1.68 for the left VIM and 6.53, -14.13, 2.10 for the right VIM. The coordinates of the mean value of the highest probability region along with the highest number of the best contacts are 5.58, 13.67, 1.33, P = 14, for the left VIM, and 6.36, -14.03, 1.11, P = 17, for the right VIM. The PFA-VIM atlas overcomes several limitations of the current anatomical atlases and can improve targeting of thalamotomies and thalamic stimulations. It is dynamic and can easily be extended with new cases.