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Functional convergence of dopaminergic and cholinergic input is critical for hippocampus-dependent working memory.
Wisman L, Sahin G, Maingay M, Leanza G, Kirik D (2008) Functional convergence of dopaminergic and cholinergic input is critical for hippocampus-dependent working memory. J Neurosci 28:7797-7807. doi: 10.1523/JNEUROSCI.1885-08.2008
Summary: Analysis of cholinergic alterations in PD patients may help to understand and treat the nonmotor symptoms of the disease.
Usage: Cholinergic neurons in theNBMand the MS/vDBB were lesioned by bilateral injection of the immunotoxin 192 IgG-SAP (0.85 µl of dissolved at a concentration of 0.142 µg/µl in PBS).
Related Products: 192-IgG-SAP (Cat. #IT-01)
Reduced cholinergic status in hippocampus produces spatial memory deficits when combined with kainic acid induced seizures.
Craig LA, Hong NS, Kopp J, McDonald RJ (2008) Reduced cholinergic status in hippocampus produces spatial memory deficits when combined with kainic acid induced seizures. Hippocampus 18(11):1112-1121. doi: 10.1002/hipo.20471
Summary: The loss of cholinergic neurons in the medial septum and seizures are both associated with Alzheimer’s disease. The authors investigated links between these factors using 192-IgG-SAP (Cat. #IT-01) and kainic acid. Rats received 0.15 µg of 192-IgG-SAP delivered to the medial septum and vertical limb of the diagonal band of Broca in four injections. Animals receiving both 192-IgG-SAP and kainic acid performed significantly worse in water maze tests than control animals, indicating that loss of cholinergic neurons and seizures interact in Alzheimer’s disease.
Related Products: 192-IgG-SAP (Cat. #IT-01)
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)
Neuromodulatory role of acetylcholine in visually-induced cortical activation: Behavioral and neuroanatomical correlates.
Dotigny F, Ben Amor AY, Burke M, Vaucher E (2008) Neuromodulatory role of acetylcholine in visually-induced cortical activation: Behavioral and neuroanatomical correlates. Neuroscience 154(4):1607-1618. doi: 10.1016/j.neuroscience.2008.04.030
Summary: Acetylcholine is thought to have a neuromodulatory role in visual processing. After rats were treated with 192-IgG-SAP (Cat. #IT-01, 2 µl of 2.4 µg/µl into the lateral ventricle) visual acuity and performance in a visual water maze task were analyzed. Lesioned animals displayed no loss in acuity, but were less able to learn a new orientation discrimination task. These data suggest that the cholinergic system in the basal forebrain plays an important role in post-synaptic visual processing.
Related Products: 192-IgG-SAP (Cat. #IT-01)
Amygdala intercalated neurons are required for expression of fear extinction.
Likhtik E, Popa D, Apergis-Schoute J, Fidacaro GA, Pare D (2008) Amygdala intercalated neurons are required for expression of fear extinction. Nature 454(7204):642-645. doi: 10.1038/nature07167
Summary: Scientists have been using fear learning in animals to study human anxiety disorders. In order to investigate the contribution of amygdala plasticity to fear learning, rats received 0.25-µl bilateral infusions of 3-µM dermorphin-SAP (Cat. #IT-12) into the amygdala. Blank-SAP (Cat. #IT-21) was used as a control. Lesioned rats displayed extinction expression deficits, indicating that the eliminated intercalated amygdala neurons play a large role in the extinction process.
Related Products: Dermorphin-SAP / MOR-SAP (Cat. #IT-12), Blank-SAP (Cat. #IT-21)
Apoptosis or Necrosis?
Q: Do targeted toxin-treated cells die by apoptosis?
A: There are, allegedly, two ways for cells to die: by apoptosis or necrosis. According to Fiorenzo Stirpe (the discoverer of saporin), saporin-intoxicated cells die both ways, some by one, others by the other.
There is good literature that states that cells die by apoptosis. Saporin and apoptosis gives 25 hits in PubMed. For instance:
Bergamaschi G, Perfetti V, et al. (1996). Saporin, a ribosome-inactivating protein used to prepare immunotoxins, induces cell death via apoptosis. Brit J Haemat 93:789-794.
However, Seeger et al., did not find evidence of apoptosis in an electron microscopy study with cells dying from 192-IgG-SAP and concluded they die from necrosis. Saporin and necrosis gives 11 hits in PubMed.
So, saporin-treated cells seem to die by both apoptosis and necrosis. The customer is always right.
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)
Read the featured article in Targeting Trends.
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Unilateral ablation of preBotzinger Complex disrupts breathing during sleep but not wakefulness.
McKay LC, Feldman JL (2008) Unilateral ablation of preBotzinger Complex disrupts breathing during sleep but not wakefulness. Am J Respir Crit Care Med 178(1):89-95. doi: 10.1164/rccm.200712-1901OC
Summary: Previous data has shown that ablation of preBötzinger complex (preBötC) neurokinin 1 expressing (NK1R) neurons disrupts breathing patterns in both sleep and wakefulness. The initial disruption is during sleep, with the eventual onset of ataxic breathing while the animals are awake. Here rats received a unilateral injection of SP-SAP (Cat. #IT-07, 6.7 ng) into the left preBötC. SP plus unconjugated saporin (Cat. #PR-01) was used as a control. Unilaterally treated rats did not develop disrupted breathing patterns during wakefulness.
Related Products: SP-SAP (Cat. #IT-07), Saporin (Cat. #PR-01)
GDNF hyperalgesia is mediated by PLCgamma, MAPK/ERK, PI3K, CDK5 and Src family kinase signaling and dependent on the IB4-binding protein versican.
Bogen O, Joseph EK, Chen X, Levine JD (2008) GDNF hyperalgesia is mediated by PLCgamma, MAPK/ERK, PI3K, CDK5 and Src family kinase signaling and dependent on the IB4-binding protein versican. Eur J Neurosci 28:12-19. doi: 10.1111/j.1460-9568.2008.06308.x
Summary: C-fiber nociceptors have been divided into NGF and GDNF classes. Here the authors examined the function of an isolectin B4-binding subpopulation of these nocicepetors. Rats received 40 ng of IB4-SAP (Cat. #IT-10) into the intrathecal space between the fifth and sixth lumbar vertebrae. The results demonstrate that GDNF sensitizes IB4+ C-fiber nociceptors and causes mechanical hyperalgesia.
Related Products: IB4-SAP (Cat. #IT-10)
Environmental enrichment mitigates the effects of basal forebrain lesions on cognitive flexibility.
De Bartolo P, Leggio MG, Mandolesi L, Foti F, Gelfo F, Ferlazzo F, Petrosini L (2008) Environmental enrichment mitigates the effects of basal forebrain lesions on cognitive flexibility. Neuroscience 154(2):444-453. doi: 10.1016/j.neuroscience.2008.03.069
Summary: The basal forebrain cholinergic system is a crucial participant in various facets of learning and memory. This work examines whether environmental enrichment can reduce the effect of cholinergic lesions on learning and memory tasks. Rats received bilateral injections of 192-IgG-SAP (Cat. #IT-01) into the cholinergic projection to the neocortex. Deficits caused by the lesion were attenuated in rats experiencing an enriched environment.
Related Products: 192-IgG-SAP (Cat. #IT-01)