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Noradrenergic innervation of the dorsal medial prefrontal cortex modulates hypothalamo-pituitary-adrenal responses to acute emotional stress.
Radley JJ, Williams B, Sawchenko PE (2008) Noradrenergic innervation of the dorsal medial prefrontal cortex modulates hypothalamo-pituitary-adrenal responses to acute emotional stress. J Neurosci 28:5806-5816. doi: 10.1523/JNEUROSCI.0552-08.2008
Summary: Hypothalamo-pituitary-adrenal (HPA) responses to emotional stress are in part controlled by the medial prefrontal cortex (mPFC). The locus ceruleus (LC) is also thought to be involved in this system, leading to the question of what interaction might exist between the mPFC and LC. Rats were injected with 90-120 nl of 0.475-µg/µl anti-DBH-SAP (Cat. #IT-03) into the cortical field containing noradrenergic neurons that project to the dorsal mPFC. The results indicate that the LC functions as an upstream component in mPFC modulation of HPA activation due to emotional stress.
Related Products: Anti-DBH-SAP (Cat. #IT-03)
Featured Article: Noradrenergic innervation of the dorsal medial prefrontal cortex modulates hypothalamo-pituitary-adrenal responses to acute emotional stress
Radley JJ (2008) Featured Article: Noradrenergic innervation of the dorsal medial prefrontal cortex modulates hypothalamo-pituitary-adrenal responses to acute emotional stress. Targeting Trends 9(3)
Related Products: Anti-DBH-SAP (Cat. #IT-03), Mouse IgG-SAP (Cat. #IT-18)
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Brainstem catecholaminergic neurons modulate both respiratory and cardiovascular function.
Li A, Emond L, Nattie E (2008) Brainstem catecholaminergic neurons modulate both respiratory and cardiovascular function. (eds. Poulin MJ, Wilson RJA). In: Integration in Respiratory Control. Advances in Experimental Medicine and Biology 605:371-376. Springer, New York, NY. doi: 10.1007/978-0-387-73693-8_65
Summary: The authors examined the role of brainstem catecholamine (CA) neurons in various aspects of breathing and chemoreception. Rats received 5-µg injections of anti-DBH-SAP (Cat. #IT-03) into the 4th ventricle; mouse IgG-SAP (Cat. #IT-18) was used as a control. This method of lesioning left the CA neurons in the peripheral nervous system intact. Lesioned animals displayed a constant decrease in breathing frequency, reduced response to CO2, and increased variability of breathing during REM sleep. Inhibitory cardiovascular effects were also seen.
Related Products: Anti-DBH-SAP (Cat. #IT-03), Mouse IgG-SAP (Cat. #IT-18)
Central chemoreception is a complex system function that involves multiple brain stem sites.
Nattie E, Li A (2009) Central chemoreception is a complex system function that involves multiple brain stem sites. J Appl Physiol 106:1464-1466. doi: 10.1152/japplphysiol.00112.2008
Summary: This short review discusses central chemoreception and the different neuronal subtypes that play roles in this process. The use of anti-SERT-SAP (Cat. #IT-23) and anti-DBH-SAP (Cat. #IT-03) is mentioned in the context of how the loss of each of these cell types affects CO2 response in rats.
Related Products: Anti-SERT-SAP (Cat. #IT-23), Anti-DBH-SAP (Cat. #IT-03)
Noradrenergic, but not cholinergic, deafferentation of prefrontal cortex impairs attentional set-shifting.
McGaughy J, Ross RS, Eichenbaum H (2008) Noradrenergic, but not cholinergic, deafferentation of prefrontal cortex impairs attentional set-shifting. Neuroscience 153:63-71. doi: 10.1016/j.neuroscience.2008.01.064
Summary: Norepinephrine and acetylcholine are involved in the mediation of attention, however, it is not yet clear whether the roles of these molecules are unique. This work utilizes a specific task shown to dissociate the roles played by the dorsolateral prefrontal cortex and the orbitofrontal cortex in primates. Rats received 5-ng infusions of anti-DBH-SAP (Cat. #IT-03) or 192-IgG-SAP (Cat. #IT-01) into each hemisphere. The type of lesion had an effect on attentional shifts and reaction to irrelevant stimuli.
Related Products: Anti-DBH-SAP (Cat. #IT-03), 192-IgG-SAP (Cat. #IT-01)
Effects of saporin-induced lesions of three arousal populations on daily levels of sleep and wake.
Blanco-Centurion C, Gerashchenko D, Shiromani PJ (2007) Effects of saporin-induced lesions of three arousal populations on daily levels of sleep and wake. J Neurosci 27:14041-14048. doi: 10.1523/JNEUROSCI.3217-07.2007
Summary: Orexin neurons in the basal forebrain, tuberomammillary nucleus (TMN), and locus ceruleus (LC) are thought to regulate arousal. Rats were injected with two or three of the following targeted conjugates: anti-DBH-SAP (Cat. #IT-03), 0.25 µl bilateral injections of 1 µg/µl into the LC; orexin-SAP (Cat. #IT-20), 0.25 µl injection of 0.25 µg/µl into the TMN; 192-IgG-SAP (Cat. #IT-01), 3 µl injection of 2 µg/µl into the lateral ventricle. Small differences were observed in sleep architecture, but the data do not support the traditional hypothesis that these three areas of the brain are essential links in the control of wake levels.
Related Products: Anti-DBH-SAP (Cat. #IT-03), Orexin-B-SAP (Cat. #IT-20), 192-IgG-SAP (Cat. #IT-01)
Prefrontal cortical norepinephrine depletion does not impair spatial working memory in rats
King M, Jentsch JD (2007) Prefrontal cortical norepinephrine depletion does not impair spatial working memory in rats. Neuroscience 2007 Abstracts 645.16/CCC18. Society for Neuroscience, San Diego, CA.
Summary: The midbrain dopamine neurons are thought to encode a reward prediction error signal (Schultz et al., 1997; Bayer & Glimcher, 2005). Parkinson’s disease (PD) is characterized by a loss of nigral dopamine neurons. Dopaminergic drugs including the dopamine precursor L-Dopa and D2 receptor agonists are taken to relieve disease symptoms. We hypothesized that patients with moderate PD (1) show atypical reinforcement learning off dopaminergic medication due to dopamine neuron loss, and (2) show more normal reinforcement learning on dopaminergic drug therapy. We developed a method to rapidly assess reinforcement learning in human subjects (Rutledge et al., SfN 2005) adapted from matching law tasks used in monkeys (Sugrue et al., 2004; Lau & Glimcher, 2005). On each trial, subjects choose one of two animated crab traps. Rewards (crabs worth $0.10) were scheduled for the two targets with different independent rates. Scheduled rewards remained available until the associated target was chosen, as in the original matching law experiments (Herrnstein, 1961). After a 5-minute training period, subjects completed 800 trials as we varied reward probabilities across blocks. PD patients (n=19) completed one session on and one off dopaminergic medication. Age-matched controls (n=21) and healthy young subjects (n=20) completed one session. We found that young and elderly control subjects had similar reinforcement learning rates, but learning rates were reduced in PD patients (when tested off medication). Learning rates in the same PD patients were restored to control levels when dopaminergic drugs were administered. We also found that the reinforcement-independent strategies of our subjects were influenced by dopamine. Young subjects tended to alternate targets independent of reward history. In contrast, elderly subjects (who suffer some dopamine neuron loss) had a tendency to perseverate in their choices. This tendency was increased in PD patients (off medication), but restored to control levels when dopaminergic drugs were administered. This effect on choice is not explained by existing models of dopamine function. These data support a role for dopamine in human reinforcement learning. Future models of decision making in reinforcement learning tasks must also account for a reward-independent effect of dopamine on choice behavior.
Related Products: Anti-DBH-SAP (Cat. #IT-03)
Locus coeruleus (LC) is involved in sustaining arousal
Gompf HS, Fuller PM, Saper CB, Lu J (2007) Locus coeruleus (LC) is involved in sustaining arousal. Neuroscience 2007 Abstracts 736.3/UU16. Society for Neuroscience, San Diego, CA.
Summary: The locus coeruleus (LC) has traditionally been thought to be involved in arousal; however, lesions of the LC have minimal effects on basal sleep-wake behavior. We propose that the LC instead may be required to sustain arousal under conditions of environmental challenge. To test this hypothesis, we intraventricularly injected saline, or 0.25, 0.5, or 1µg anti-DBH-saporin (DBH-SAP selectively lesions the LC), and implanted EEG/EMG electrodes. On recording days, each animal was paired with a normal rat (social interaction) and presented with novel objects every hour for 5 hours from ZT 6 to ZT 11. We then repeated the same experiment for 2.5 hrs and immunostained tissue for Fos and TH or Fos and DBH. We also repeated the same experiment in rats with unilateral LC lesion by 6-OHDA. During 5 hr of stimulation with novel objects and social interaction (distracting stimuli, DS), controls or partial LC lesioned animals (0.25 µg DBH-SAP) spent 83 ± 8% and 92 ± 4% awake respectively (n = 3 and 4, p = 0.4) whereas animals with complete LC lesions (0.5 and 1 µg) spent significantly less time in wakefulness (59 ± 4% and 66 ± 5% respectively, n = 3 and 4, p = 0.0005). The reduction of wakefulness occurred primarily during the second 30 mins of each hour. Following DS exposure, Fos was highly expressed in the cerebral cortex in both LC lesioned groups and controls. Furthermore, we found a correlation (R2 = 0.79) between the remaining LC neurons and wakefulness under DS. Rats with loss of one LC showed no changes in wakefulness, and Fos was highly and symmetrically induced in the cerebral cortex. Our results suggest that the LC is specifically involved in sustaining arousal.
Related Products: Anti-DBH-SAP (Cat. #IT-03)
Noradrenergic denervation of dorsal medial prefrontal cortex (mPFC) modulates paraventricular hypothalamic responses to acute restraint stress
Radley JJ, Sawchenko PE (2007) Noradrenergic denervation of dorsal medial prefrontal cortex (mPFC) modulates paraventricular hypothalamic responses to acute restraint stress. Neuroscience 2007 Abstracts 198.4/ZZ13. Society for Neuroscience, San Diego, CA.
Summary: The dorsal mPFC is implicated in restricting the hypothalamo-pituitary-adrenal (HPA) axis response to acute emotional stress via its influence on neuroendocrine effector mechanisms represented in the paraventricular hypothalamic nucleus (PVH). The afferents that provide for mPFC engagement during stress may include ascending noradrenergic projections from the locus coeruleus (LC), which are known to be stress-responsive and capable of modulating attentional mechanisms and other aspects of mPFC function. Arguing against such a role for LC-mPFC projections is evidence that LC lesions attenuate PVH/HPA responses to acute emotional stress. Here we sought to clarify the role of the noradrenergic innervation of mPFC in acute stress-induced PVH activation. Rats received injections of the axonally transported catecholamine immunotoxin, anti-dopamine-β-hydroxylase (DBH)-saporin, centered in the prelimbic area, or sham injections of IgG-saporin or saline. 14 days later, rats were subjected to 30 min of restraint and perfused 2 h later. Immunohistochemical localization of the immediate-early gene product, Fos, was employed as an index of cellular activation in PVH. Cell counts revealed that acute stress reliably provoked marked increases in the number of Fos-labeled neurons in the PVH of all restrained groups relative to unstressed controls. Among stressed groups, anti-DBH-saporin lesions in the dorsal mPFC decreased activational responses in the PVH by 30%, relative to sham-lesioned animals, that were focused in the hypophysiotropic (dorsal medial parvocellular) subdivision. DBH immunostaining revealed a virtually complete noradrenergic denervation of the prelimbic area in immunotoxin-treated animals, while the ventral mPFC (infralimbic area) remained intact. Cortical fields dorsally and laterally adjoining the target area displayed a partial denervation, consistent with local collateralization of prelimbic-projecting LC neurons. While these data are consistent with a role for LC-mPFC projections in facilitating restraint-induced PVH engagement, it remains to be determined how this perspective may be reconciled with prior evidence indicating that mPFC serves normally to inhibit PVH/HPA responses to acute emotional stress.
Related Products: Anti-DBH-SAP (Cat. #IT-03)
Experimental dissociation of neural circuits underlying conditioned avoidance and hypophagic responses to lithium chloride.
Rinaman L, Dzmura V (2007) Experimental dissociation of neural circuits underlying conditioned avoidance and hypophagic responses to lithium chloride. Am J Physiol Regul Integr Comp Physiol 293(4):R1495-1503. doi: 10.1152/ajpregu.00393.2007
Summary: Lithium chloride (LiCl) is frequently used to study neural attributes of “sickness behavior.” Previous work by these authors showed that noradrenergic neurons (NA) in the nucleus of the solitary tract (NST) are involved in the inhibition of food uptake by cholecystokinin. Here, 20 ng total of anti-DBH-SAP (Cat. #IT-03) was injected into the NST of rats. Lesioned animals demonstrated significantly reduced inhibition of food intake in response to LiCl, but conditioned flavor avoidance was left intact.
Related Products: Anti-DBH-SAP (Cat. #IT-03)