Targeting Topics 09q3

Photostimulation of retrotrapezoid nucleus phox2b-expressing neurons in vivo produces long-lasting activation of breathing in rats

Abbott SB, Stornetta RL, Fortuna MG, Depuy SD, West GH, Harris TE, Guyenet PG

J Neurosci 29(18):5806-5819, 2009.

The retrotrapezoid nucleus (RTN) contains a subpopulation of cells that are thought to function as central respiratory chemoreceptors. The authors used bilateral 22-ng injections of anti-DBH-SAP (Cat. #IT-03) into the lateral horn of the second thoracic segment to investigate this hypothesis. Coupled with data generated by lentivirus-driven transgenic expression of a light-activated cationic channel, it is demonstrated that noncatecholaminergic neurons in the RTN function as central respiratory chemoreceptors.

Anti-amnesic properties of (+/-)-PPCC, a novel sigma receptor ligand, on cognitive dysfunction induced by selective cholinergic lesion in rats

Antonini V, Prezzavento O, Coradazzi M, Marrazzo A, Ronsisvalle S, Arena E, Leanza G

J Neurochem 109(3):744-754, 2009.

Sigma-1 receptors are found throughout the central nervous system, and are thought to be a target for regenerative therapy in Alzheimer’s disease. Rats received 3.0 µg or 5.0 µg of 192-IgG-SAP (Cat. #IT-01) injected intracerebroventricularly. The lesioned animals displayed dose-dependent deficits in water maze performance. Treatment with the sigma-1 receptor agonist (±)-PPCC significantly improved both reference and working memory performance in treated animals, indicating that (±)-PPCC-mediated positive effects are probably a function of the sigma-1 receptor.

Cholinergic deafferentation of the neocortex using 192 IgG-saporin impairs feature binding in rats

Botly LC, De Rosa E

J Neurosci 29(13):4120-4130, 2009.

It has been hypothesized that the nucleus basalis magnocellularis (NBM) is the source of cholinergic input to the neocortex that is responsible for incorporating different features of an object into a unified neural representation of said object. Rats received 0.04-µg bilateral injections of 192-IgG-SAP (Cat. #IT-01) into the NBM. In lesioned animals modes of learning requiring feature binding were impaired, while processes not using feature binding were left intact.

Severe Scene Learning Impairment, but Intact Recognition Memory, after Cholinergic Depletion of Inferotemporal Cortex Followed by Fornix Transection

Browning PG, Gaffan D, Croxson PL, Baxter MG

Cereb Cortex 20(2):282-293, 2010.

In this work the authors investigated the link between connections carried by the fornix and cholinergic input to the inferotemporal cortex in scene learning. Monkeys received 56-64 0.02-µg injections of ME20.4-SAP (Cat. #IT-15) into the inferotemporal cortex, and entorhinal cortices. There was a marked impairment in memory for lesioned animals that also received a fornix transection, indicating a synergistic interaction between connections carried by the fornix and cholinergic input to the inferotemporal cortex for episodic memory.

Substance P neurotransmission and violent aggression: the role of tachykinin NK1 receptors in the hypothalamic attack area

Halasz J, Zelena D, Toth M, Tulogdi A, Mikics E, Haller J

Eur J Pharmacol 611(1-3):35-43, 2009.

Stimulation of the hypothalamic attack area elicits biting attacks in rats. The authors eliminated NK1 receptor-expressing neurons in this area with bilateral 6.25-ng injections of SP-SAP (Cat. #IT-07). Violent attacks were dramatically reduced while milder forms of aggression remained unchanged, indicating that these two forms of aggression are controlled via different pathways. Lesioned animals also displayed reduced anxiety-like behavior in the elevated plus-maze, suggesting a connection between the hypothalamic attack area and brain areas controlling anxiety.

Partial ablation of mu-opioid receptor rich striosomes produces deficits on a motor-skill learning task

Lawhorn C, Smith DM, Brown LL

Neuroscience 163(1):109-119, 2009.

The functional role of basal ganglia striosomes is not well understood. In order to examine these cells in the context of motor behavior the authors injected 8.5 ng of dermorphin-SAP (Cat. #IT-12) into several areas of the striatum of mice (saporin, Cat. #PR-01, was used as a control). The animals were then evaluated in complex motor tasks involving the use of striatal circuitry. Animals receiving dermorphin-SAP showed deficits in specific motor tasks corresponding to the extent of the lesion.

Targeted ablation of cardiac sympathetic neurons reduces resting, reflex and exercise-induced sympathetic activation in conscious rats

Lujan HL, Palani G, Chen Y, Peduzzi JD, Dicarlo SE

Am J Physiol Heart Circ Physiol 296(5):H1305-1311, 2009.

Excessive sympathetic activity contributes to most cardiovascular diseases. Thoracic sympathectomy is a non-specific treatment that can alleviate some sympathetic activity, but produces undesirable side effects. The authors lesioned a subset of sympathetic preganglionic neurons with 10 µg of CTB-SAP (Cat. #IT-14) into the left and right stellate ganglion of rats. Treated animals displayed several types of reduced cardiac sympathetic neuronal activity indicating that this may be a useful approach for treating these types of conditions.

Neuroprotective effects of the anti-inflammatory compound triflusal on ischemia-like neurodegeneration in mouse hippocampal slice cultures occur independent of microglia

Montero Dominguez M, Gonzalez B, Zimmer J

Exp Neurol 218(1):11-23, 2009.

In this work the authors looked to clarify the role of microglia in an experimental stroke model. Hippocampal slices were subject to oxygen-glucose deprivation to establish the stroke model. Slices were exposed to 1.3 nM Mac-1-SAP (Cat. #IT-06) for 7 days prior to the experiments. This treatment depleted virtually all of the microglia. See Cover Story for details.

Central chemoreception is a complex system function that involves multiple brain stem sites

Nattie E, Li A

J Appl Physiol 106(4):1464-1466, 2009.

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.

Neurotrophic signaling molecules associated with cholinergic damage in young and aged rats: Environmental enrichment as potential therapeutic agent

Paban V, Chambon C, Manrique C, Touzet C, Alescio-Lautier B

Neurobiol Aging 32(3):470-485, 2011.

This study examined the potential of long-term environmental enrichment as a therapeutic agent for cholinergic damage. Rats received bilateral injections of 192-IgG-SAP (Cat. #IT-01) into the medial septum (37.5 ng per side) and nucleus basalis magnocellularis (75 ng per side). Through the use of cDNA macroarrays the authors associated the therapeutic effects of environmental enrichment with downregulation of gene expression associated with certain cell processes, and upregulation of gene expression associated with signal transduction.

A discrete GABAergic relay mediates medial prefrontal cortical inhibition of the neuroendocrine stress response

Radley JJ, Gosselink KL, Sawchenko PE

J Neurosci 29(22):7330-7340, 2009.

GABAergic neurons have been implicated in the negative regulation of the hypothalamic-pituitary-adrenal axis (HPA). In order to clarify GABAergic input to the paraventricular hypothalamic nucleus the authors injected 0.23 µg of GAT1-SAP
(Cat. #IT-32) into the anterior bed nucleus of the stria terminalis. Both unilateral and bilateral injections were used. Rabbit IgG-SAP (Cat. #IT-35) was used as a control. The data indicate that the GABAergic neuronal population functions as proximate mediator of HPA-inhibitory limbic influences.

Neuropathic pain is maintained by brainstem neurons co-expressing opioid and cholecystokinin receptors

Zhang W, Gardell S, Zhang D, Xie JY, Agnes RS, Badghisi H, Hruby VJ, Rance N, Ossipov MH, Vanderah TW, Porreca F, Lai J

Brain 132(Pt 3):778-787, 2009.

A subpopulation of rostral ventromedial medulla (RVM) neurons express both the mu opioid receptor (MOR) and the cholecystokinin type 2 receptor (CCK2). The authors tested the hypothesis that co-expression of these receptors is necessary for maintaining neuropathic pain. Rats received 50-ng bilateral injections of dermorphin-SAP (Cat. #IT-12), CCK-SAP (Cat. #IT-31), or the control (saporin alone, Cat. #PR-01) into the RVM. The data indicate that neurons co-expressing these receptors facilitate pain and can be directly activated by CCK input to the RVM.

The basal forebrain cholinergic system is required specifically for behaviorally mediated cortical map plasticity

Ramanathan D, Tuszynski MH, Conner JM

J Neurosci 29(18):5992-6000, 2009.

In this work the authors examined what types of neuronal plasticity require the cholinergic system. Selective depletion of the basal forebrain cholinergic system was accomplished by bilateral 112-ng and 75-ng injections of 192-IgG-SAP (Cat. #IT-01) into the nucleus basalis magnocellularis/ substantia inominata. The results indicate a linkage between cholinergic mechanisms and distinct forms of cortical plasticity, supporting the role of the forebrain cholinergic system in modulating plasticity associated with behavioral experience.

Ablation of least shrew central neurokinin NK1 receptors reduces GR73632-induced vomiting

Ray AP, Chebolu S, Ramirez J, Darmani NA

Behav Neurosci 123(3):701-706, 2009.

In this work the authors investigated the role of central and peripheral nervous systems components that mediate the emetic reflex. Least shrews received a 600-ng injection of SSP-SAP (Cat. #IT-11) into the lateral ventricle. Some animals also received a 4.8-µg intraperitoneal injection of SSP-SAP. Blank-SAP (Cat. #IT-21) and unconjugated saporin (Cat. #PR-01) were used as controls. Lesioned animals displayed reduced emesis, but the data indicate that a minor peripheral nervous system component is also present.

Neuropeptide Y receptor-expressing dorsal horn neurons: role in nocifensive reflex responses to heat and formalin

Wiley RG, Lemons LL, Kline RH 4th

Neuroscience 161(1):139-147, 2009.

In order to clarify the role of dorsal horn Y1 neuropeptide Y receptors (Y1R) in nocifensive responses to aversive stimuli, the authors injected 500-750 ng of NPY-SAP (Cat. #IT-28) into the intrathecal space of rats. Blank-SAP (Cat. #IT-21) was used as a control. Lesioned animals displayed specific loss of Y1R and increased latencies on several reflex response tests indicating a role for Y1R in nociception.