scholarly journals Optimization of whole-brain rabies virus tracing technology for small cell populations

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Theresia J. M. Roelofs ◽  
Shanice Menting-Henry ◽  
Lieke M. Gol ◽  
Annelijn M. Speel ◽  
Vera H. Wielenga ◽  
...  

AbstractThe lateral hypothalamus (LH) is critically involved in the regulation of homeostatic energy balance. Some neurons in the LH express receptors for leptin (LepRb), a hormone known to increase energy expenditure and decrease energy intake. However, the neuroanatomical inputs to LepRb-expressing LH neurons remain unknown. We used rabies virus tracing technology to map these inputs, but encountered non-specific tracing. To optimize this technology for a minor cell population (LepRb is not ubiquitously expressed in LH), we used LepRb-Cre mice and assessed how different titers of the avian tumor virus receptor A (TVA) helper virus affected rabies tracing efficiency and specificity. We found that rabies expression is dependent on TVA receptor expression, and that leakiness of TVA receptors is dependent on the titer of TVA virus used. We concluded that a titer of 1.0–3.0 × 107 genomic copies per µl of the TVA virus is optimal for rabies tracing. Next, we successfully applied modified rabies virus tracing technology to map inputs to LepRb-expressing LH neurons. We discovered that other neurons in the LH itself, the periventricular hypothalamic nucleus (Pe), the posterior hypothalamic nucleus (PH), the bed nucleus of the stria terminalis (BNST), and the paraventricular hypothalamic nucleus (PVN) are the most prominent input areas to LepRb-expressing LH neurons.

2021 ◽  
Vol 22 (2) ◽  
pp. 759
Author(s):  
Karen P. Briski ◽  
Mostafa M. H. Ibrahim ◽  
A. S. M. Hasan Mahmood ◽  
Ayed A. Alshamrani

The catecholamine norepinephrine (NE) links hindbrain metabolic-sensory neurons with key glucostatic control structures in the brain, including the ventromedial hypothalamic nucleus (VMN). In the brain, the glycogen reserve is maintained within the astrocyte cell compartment as an alternative energy source to blood-derived glucose. VMN astrocytes are direct targets for metabolic stimulus-driven noradrenergic signaling due to their adrenergic receptor expression (AR). The current review discusses recent affirmative evidence that neuro-metabolic stability in the VMN may be shaped by NE influence on astrocyte glycogen metabolism and glycogen-derived substrate fuel supply. Noradrenergic modulation of estrogen receptor (ER) control of VMN glycogen phosphorylase (GP) isoform expression supports the interaction of catecholamine and estradiol signals in shaping the physiological stimulus-specific control of astrocyte glycogen mobilization. Sex-dimorphic NE control of glycogen synthase and GP brain versus muscle type proteins may be due, in part, to the dissimilar noradrenergic governance of astrocyte AR and ER variant profiles in males versus females. Forthcoming advances in the understanding of the molecular mechanistic framework for catecholamine stimulus integration with other regulatory inputs to VMN astrocytes will undoubtedly reveal useful new molecular targets in each sex for glycogen mediated defense of neuronal metabolic equilibrium during neuro-glucopenia.


1989 ◽  
Vol 257 (1) ◽  
pp. R246-R251 ◽  
Author(s):  
M. Lisa ◽  
E. Marmo ◽  
J. H. Wible ◽  
J. A. DiMicco

We have previously shown that the physiological and behavioral manifestations of emotional stress are produced when drugs impairing gamma-aminobutyric acid (GABA)-mediated synaptic inhibition are injected into the posterior hypothalamic nucleus in rats [Wible, J.H., Jr., F.C. Luft, and J.A. DiMicco. Am. J. Physiol. 254 (Regulatory Integrative Comp. Physiol. 23): R680-R687, 1988]. The purpose of this study was to assess further the potential role of GABA receptors in this region in the response to stress using muscimol, a GABAA receptor agonist. In six chronically instrumented conscious rats, air stress after vehicle treatment evoked marked and sustained tachycardia (+130 +/- 14 beats/min at +10 min) accompanied by a less dramatic increase in arterial pressure (+14 +/- 3 mmHg). Microinjection of muscimol (10 ng; 88 pmol) at the same posterior hypothalamic site in which GABA blockade causes cardiovascular changes similar to those seen in stress produced a modest depression of cardiovascular function in unstressed animals (-28 +/- 5 beats/min and -6 +/- 3 mmHg). However, similar treatment with muscimol virtually abolished the stress-induced tachycardia in the same rats (+9 +/- 8 beats/min), while having no significant effect on baroreflex-evoked increases in heart rate caused by intravenous infusion of sodium nitroprusside (4 micrograms). These findings support a role for activation of neurons in the posterior nucleus of the hypothalamus in the generation of stress-induced cardiovascular changes and for control of this mechanism by local GABA receptors.


2021 ◽  
Author(s):  
Kay Tye ◽  
Gillian Matthews ◽  
Mackenzie Lemieux ◽  
Elizabeth Brewer ◽  
Raymundo Miranda ◽  
...  

Abstract Affiliative social connections facilitate well-being and survival in numerous species. Engaging in social interactions requires positive and negative motivational drive, elicited through coordinated activity across neural circuits. However, the identity, interconnectivity, and functional encoding of social information within these circuits remains poorly understood. Here, we focused on downstream projections of dorsal raphe nucleus (DRN) dopamine neurons (DRNDAT), which we previously implicated in ‘negative drive’-induced social motivation. We show that three prominent DRNDAT projections – to the bed nucleus of the stria terminalis (BNST), central amygdala (CeA), and posterior basolateral amygdala (BLP) – play separable roles in behavior, despite substantial collateralization. Photoactivation of the DRNDAT-CeA projection promoted social behavior and photoactivation of the DRNDAT-BNST projection promoted exploratory behavior, while the DRNDAT-BLP projection supported place avoidance, suggesting a negative affective state. Downstream regions showed diverse, region-specific, receptor expression, poising DRNDAT neurons to act through dopamine, neuropeptide, and glutamate transmission. Furthermore, we show ex vivo that the effect of DRNDAT photostimulation on downstream neuron excitability was predicted by baseline cell properties, suggesting cell-type-specific modulation. Collectively, these data indicate that DRNDAT neurons may bias behavior via precise modulation of cellular activity in broadly-distributed target structures.


1991 ◽  
Vol 261 (3) ◽  
pp. H814-H824 ◽  
Author(s):  
J. R. Martin ◽  
M. M. Knuepfer ◽  
T. C. Westfall

Unilateral microinjection of neuropeptide Y (NPY) into the posterior hypothalamic nucleus was previously found to evoke a sympathoexcitatory-mediated increase in mean arterial pressure (MAP) in urethan-anesthetized rats. In this study, the effect of unilateral injection of NPY into the posterior hypothalamic nucleus on the cardiovascular system of conscious, freely moving rats was determined. Microinjection of NPY (0.2-2.4 nmol) or the cholinergic agonist carbachol (0.5-5.5 nmol) resulted in concentration-dependent increases in MAP. Pretreatment of animals with 7.5 mg/kg iv of the ganglionic blocker pentolinium resulted in a blockade of the increase in MAP evoked by microinjection of NPY (2.4 nmol) or carbachol (3.3 nmol). Despite their similarity of effects on MAP, NPY and carbachol evoked different changes in heart rate. NPY increased heart rate, whereas carbachol evoked a biphasic change in heart rate that consisted of an initial increase followed by a decrease. In addition, carbachol caused increases in both hindquarter and mesenteric vascular resistances, whereas NPY caused a short-lasting increase in mesenteric resistance and a tendency toward an increase in hindquarter resistance. Both NPY and carbachol increased total peripheral resistance while NPY decreased stroke volume. Cardiac output was not significantly affected by either NPY or carbachol, although NPY had a tendency to decrease cardiac output. These results suggest that microinjection of NPY or carbachol into the posterior hypothalamic nucleus of conscious rats evokes an increase in MAP primarily as a result of sympathoexcitation and that NPY and carbachol selectively affect autonomic nervous system control of the cardiovascular system.


NeuroImage ◽  
2011 ◽  
Vol 56 (1) ◽  
pp. 35-44 ◽  
Author(s):  
Calvin K. Young ◽  
Andrew R. Brown ◽  
Jordan H.B. Robinson ◽  
Ursula I. Tuor ◽  
Jeff F. Dunn ◽  
...  

Author(s):  
Devendra Pathak ◽  
Neelam Bansal

Background: Hypothalamus is an integral part of the hypothalamo-hypophyseal ovarian axis. It contains several small nuclei that have been implicated in several specialized functions. It is the master endocrine gland because it regulates the activity of the pituitary. The present investigation was planned to elucidate the histomorphological details of different nuclei in the hypothalamus of Indian buffaloes. Methods: The hypothalami of buffaloes (n =52) were collected from local abattoirs and Teaching Veterinary Clinical Complex, GADVASU, Ludhiana. The tissue samples were collected from three levels i.e. the supraoptic, tuberal and the mamillary region of the hypothalamus and processed for paraffin sectioning and the sections were stained with various stains for histomorphological studies. Result: The well-defined cell groups or nuclei were identified both in the coronal and sagittal sections of the hypothalamus in all the reproductive phases. Eight nuclei were distinctly recognized in buffalo hypothalamus at three levels in the coronal sections of the hypothalamus. At the level of optic chiasma, the nuclei were paraventricular nucleus (PVN), supraoptic nucleus (SON) and preopticnucleus (PON); at the tuberal region, there were arcuate nucleus (AN) and ventromedial nucleus (VMN) and at the mammillary region, the lateral mammillary nucleus (LMN), medial mammillary nucleus (MMN) and posterior hypothalamic nucleus (PHN) were identified. Most of the nuclei consisted of a loose or compact heterogeneous collection of neurons. The neurons of the different nuclei were of variable shape. The cytoplasm contained a varied amount of Nissl material. The neurosecretory substance was peripheral in position. Small to large-sized blood vessels were observed in between the neuronal substance. The size of the neurons varied during different stages of reproduction.


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