Targeting Topics 02q2

GABAergic septohippocampal neurons are not necessary for spatial memory.

Pang KC, Nocera R, Secor AJ, Yoder RM.

Hippocampus 11(6):814-827, 2001. PMID: 11811676

The medial septum and diagonal band of Broca (MSDB) are necessary for spatial memory. Both cholinergic and GABAergic neuronal populations are present in the MSDB. 192-Saporin (Cat. #IT-01) was used to eliminate cholinergic populations and kainic acid was used to reduce numbers of GABAergic neurons. Both agents were injected (independently or in combination) into the medial septum and each diagonal band of rats (192-Saporin 250 ng MS, 150 ng DB) to determine the importance of GABAergic neurons in the MSDB for spatial memory. The results showed elimination of GABAergic neurons has no impact on spatial memory, while elimination of cholinergic neurons has a mild impact.

Selective immunolesioning of cholinergic neurons in nucleus basalis magnocellularis impairs prepulse inhibition of acoustic startle.

Ballmaier M, Casamenti F, Zoli M, Pepeu G, Spano P.

Neuroscience 108(2):299-305, 2001. PMID: 11734362

One of the measures for schizophrenia is a deficit in sensorimotor gating (the ability of the brain to filter sensory input to focus on selective stimuli) measured by prepulse inhibition (PPI) of the startle reflex. The authors injected 300 nl of 400 ng/μl 192-Saporin (Cat. #IT-01) into each side of the nucleus basalis magnocellularis (NBM) in rats to examine the effect of NBM cholinergic neuron elimination on the startle reflex. The data show a significant, persistent disruption of the PPI independent of the amplitude of the startle reflex. This suggests the NBM may play an important role in information processing in schizophrenia.

Lack of effect of moderate Purkinje cell loss on working memory.

Wrenn CC, Wiley RG.

Neuroscience 107(3):433-445, 2001. PMID: 11718998

When 192-Saporin (Cat. #IT-01) is injected intracerebroventricularly, some p75-expressing cerebellar Purkinje cells are eliminated along with cholinergic neurons. To verify that the effects of basal forebrain lesions on working memory were not caused by loss of these Purkinje cells the authors compared doses of 1 μg OX7-SAP (Cat. #IT-02) and either 2 μg or 4 μg of 192-Saporin injected into the lateral ventricle. The data show that although similar amounts of Purkinje cells were eliminated by OX7-SAP and the lower dose of 192- Saporin, no working memory deficits resulted. Only the 4-μg dose of 192- Saporin produced working memory deficits, they conclude that this is not due to Purkinje cell loss, but the loss of cholinergic neurons.

Central cholinergic depletion induced by 192 IgG-saporin alleviates the sedative effects of propofol in rats.

Pain L, Jeltsch H, Lehmann O, Lazarus C, Laalou FZ, Cassel JC.

Br J Anaesth 85(6):869-873, 2000. PMID: 11732522

In order to examine the effect of cholinergic depletion on the sedative potency of propofol in rats the authors injected 1 μg of 192-Saporin (Cat. #IT-01) into each lateral ventricle. The findings indicate a ~50% reduction in sedative potency in lesioned rats.

Transverse patterning reveals a dissociation of simple and configural association learning abilities in rats with 192 IgG-saporin lesions of the nucleus basalis magnocellularis.

Butt AE, Bowman TD.

Neurobiol Learn Mem 77(2):211-233, 2002. PMID: 11848720

Using 80 ng bilateral infusions of 192-Saporin (Cat. #IT-01) into each of the medial and lateral target sites of the nucleus basalis magnocellularis (NBM) in rats, the authors demonstrate that lesioning the cholinergic systems of the NBM impairs a more complicated learning technique, while leaving simple association learning intact. The results also show that the transition between these two learning strategies is impaired in lesioned animals.

Facilitation of dopamine-mediated locomotor activity in adult rats following cholinergic denervation.

Mattsson A, Ogren SO, Olson L.

Exp Neurol 174(1):96-108, 2002. PMID: 11869038

It has been hypothesized that hyperactivity of dopaminergic systems is involved in schizophrenia. The authors examine the effect of central cholinergic denervation on dopamine-mediated functions. Adult rats received bilateral injections of 2.5 μg of 192-Saporin (Cat. #IT-01) into the lateral ventricles. Neonatal rats received 400 ng 192-Saporin in bilateral i.c.v. injections. The results indicate that severe cholinergic deficiencies in the forebrain can lead to dopaminergic overfunction, one of the possible mechanisms in schizophrenia.

Isoflurane and nociception: spinal alpha2A adrenoceptors mediate antinociception while supraspinal alpha1 adrenoceptors mediate pronociception.

Kingery WS, Agashe GS, Guo TZ, Sawamura S, Davies MF, Clark JD, Kobilka BK, Maze M.

Anesthesiology 96(2):367-374, 2002. PMID: 11818770

The authors injected 3 μg/3 μl of anti-DBH-SAP (Cat. #IT-03) into the lateral ventricle of rats to determine whether noradrenergic brainstem nuclei and descending spinal pathways are responsible for the antinociceptive actions of isoflurane. The results indicate that isoflurane modulates nociception by as many as three mechanisms, utilizing various combinations of noradrenergic neurons, adrenoceptors, and descending spinal pathways.

Cytotoxic targeting of isolectin IB4-binding sensory neurons.

Vulchanova L, Olson TH, Stone LS, Riedl MS, Elde R, Honda CN.

Neuroscience 108(1):143-155, 2001. PMID: 11738138

Vulchanova et al. examine the role of IB4-binding neurons in nociception. IB4-SAP (Cat. #IT-10) was injected into rats (2 μg in left sciatic nerve). The resulting ablation of IB4-binding neurons provides evidence for their role in nociceptive processing and demonstrates a rapid compensatory response to signalling of acute pain.

Lesions of the nucleus basalis magnocellularis induced by 192 IgG-saporin block memory enhancement with posttraining norepinephrine in the basolateral amygdala.

Power AE, Thal LJ, McGaugh JL.

Proc Natl Acad Sci U S A 99(4):2315-2319, 2002. PMID: 11830635

There is evidence that memory consolidation (retention) can be modulated by drugs and stress hormones acting in the basolateral amygdala (BLA). The BLA sends projections to the nucleus basalis magnocellularis (NBM), which in turn sends cholinergic projections to the neocortex. The authors used 100 ng bilateral infusions of 192-Saporin (Cat. #IT-01) in 500 nl 0.1 M PBS to investigate whether lesions of the cholinergic NBM projections affect BLA modulation of memory. 192- Saporin lesions blocked memory enhancement normally induced by norepinephrine infusions into the BLA. This finding suggests NBM- cortex projections may mediate BLA modulation of memory storage or processing in the neocortex.

Cholinergic and noncholinergic septal neurons modulate strategy selection in spatial learning.

Cahill JF, Baxter MG.

Eur J Neurosci 14(11):1856-1864, 2001. PMID: 11860481

The authors compared ibotenic acid (IA)-treated rats with those injected with 45 ng and 30 ng of 192-Saporin (Cat. #IT-01) into two separate coordinates of the medial septum/vertical limb of the diagonal band (MS/VDB) to investigate the role of basal forebrain projections in modulating strategy selection in spatial learning. While rats with IA lesions in the MS/VDB demonstrated significant disruption of the learning process, the 192-Saporin-lesioned rats did not show this effect.