sfn2002

Truitt WA, McKenna KE, Coolen LM (2002) Lesions of spinothalamic neurons in lumbar spinal cord disrupt ejaculatory reflexes in male rats. Neuroscience 2002 Abstracts 69.2. Society for Neuroscience, Orlando, FL.

Summary: Previously we tested the significance of a population of lumbar spinothalamic (LUST) cells for male sexual behavior in rats. Anatomically, LUST cells are positioned to relay ejaculation-related sensory signals from reproductive organs to the brain and express substance P receptors as well as several neuropeptides including galanin. Ablation of LUST neurons by the selective toxin SSP-saporin resulted in a complete disruption of ejaculatory behavior. These results suggested that LUST cells play a pivotal role in generation of ejaculatory behavior and may be part of a spinal ejaculation generator. To test this hypothesis, we investigated ejaculatory reflexes in male rats with LUST lesions, using the urethrogenital reflex model. SSP-saporin (4 ng/µl) was injected bilaterally into L3-L4 region in sexually experienced male Sprague Dawley rats. Ten days following surgery, animals were deeply anesthetized and spinal cords were transected at upper thoracic levels. Next, urethral stimulation was provided and muscle contractions were recorded in the bulbocavernous muscle (BCM). Following the experiment, animals were sacrificed and lesions were confirmed using immunostaining for galanin, a marker for LUST cells. In non-lesioned animals (n=5), urethral stimulation produced stereotypical reflex contraction of the BCM, and penile reflexes were observed. In contrast, in animals with complete lesions of LUST cells (n=5) the urogenital reflex was severely attenuated. These results indicate that LUST cells are involved in control of ejaculatory reflexes and are part of a spinal ejaculation generator. Supported by: NIH R01 MH60781(LMC)

Related Products: SSP-SAP (Cat. #IT-11)

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Mattsson A, Lindqvist E, Ögren SO, Olson L (2002) Amphetamine hyperresponses in cholinergically denervated rats and alpha7 nAChR knockout mice, and effects of nicotinic agonists. Neuroscience 2002 Abstracts 136.7. Society for Neuroscience, Orlando, FL.

Summary: We have recently shown that cholinergic denervation of the basal forebrain in adult rats, using intracerebroventricular injections of the cholinergic immunotoxin 192-saporin, leads to overreactivity in dopaminergic systems, in the form of enhanced amphetamine-induced hyperactivity. This increased sensitivity to amphetamine in cholinergically denervated rats can be partially counteracted by nicotine if given before the amphetamine challenge. The results provide a possible link between deficits in central cholinergic systems and overactivity in dopaminergic systems, which might be of relevance for the pathogenesis of schizophrenia. To further evaluate the role of cholinergic dysfunction for dopaminergic hyperactivity we have focused on the α7 nAChR due to its presumed involvement in schizophrenia. First, we tested if a selective α7 nAChR agonist, AR-R17779, could mimic the effect of nicotine (partial blockade of amphetamine hyperresponse) in cholinergically denervated rats. Second, we tested if mice lacking the α7 nAChR gene have a similar increased sensitivity to amphetamine, as cholinergically denervated rats. Preliminary results from these studies show that AR-R17779 normalizes the effect of amphetamine cholinergically denervated rats, and further, that lack of the α7 nAChR gene leads to an increased sensitivity to amphetamine. Cholinergic deficiencies that cause dopaminergic overactivity are compatible with a role of the α7 nAChR in schizophrenia and may suggest a role for the cholinergic system in other psychotic states.

Related Products: 192-IgG-SAP (Cat. #IT-01)

Dinh TT, Duffy P, Ritter S (2002) Immunotoxin lesion of spinally projecting catecholamine neurons impairs the adrenal medullary response to glucoprivation and the sympathetic response to forced swim. Neuroscience 2002 Abstracts 76.5. Society for Neuroscience, Orlando, FL.

Summary: Distinct populations of hindbrain catecholamine neurons project spinally to innervate sympathetic and adrenal medullary preganglionic neurons. Previously we injected the immunotoxin, saporin conjugated to anti-dopamine beta hydroxylase (DSAP), into the spinal cord to selectively lesion these neurons. DSAP lesions abolished adrenal medullary Fos expression following insulin-induced hypoglycemia or 2-deoxy-D-glucose (2DG) and eliminated the hyperglycemic response to 2DG, which is mediated by adrenal medullary epinephrine (E) secretion. Here we examine the plasma E and norepinephrine (NE) responses to 2DG (250 mg/kg, s.c.) and to 5 min of forced swim in rats injected at T2-T4 with DSAP or unconjugated saporin (SAP) control solution. Blood was sampled remotely via jugular catheters between 0 and 240 min after 2DG or swim. Immunohistochemistry confirmed loss of dopamine B-hydroxylase throughout the spinal cord of DSAP rats. In DSAPs, both plasma E and hyperglycemic responses to 2DG were abolished or severely impaired compared to SAPs. 2DG did not elevate plasma NE in either group. Swim stress increased NE in both SAPs and DSAPs, but the DSAP response was only 60% of the SAP response. Results show for the first time that the selective activation of the adrenal medulla by glucoprivation, described previously, is mediated by spinally projecting catecholamine neurons. Results also demonstrate that spinal catecholamine terminals, presumeably arising from different hindbrain neurons, contribute to, but are not entirely responsible for, sympathetic neuronal responses to swim stress.

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Varga C, Grosche J, Brauer K, Seeger J, Harkany T, Hartig W (2002) Cholinergic neurons in the rabbit forebrain: Chemoarchitecture, in vivo labeling, immunolesions. Neuroscience 2002 Abstracts 35.3. Society for Neuroscience, Orlando, FL.

Summary: While the rabbit basal forebrain and its cholinergic components became useful targets for modeling of neuropathological changes associated with Alzheimer’s disease, their neuroanatomical organization is still largely elusive. Hence, we focused on (i) the number of cholinergic basal forebrain neurons (CBFN)in the major nuclei based on choline acetyltransferase (ChAT) immunoperoxidase labeling, (ii) the density of ChAT-immunoreactive fibers in distinct neocortical and hippocampal areas, (iii) mapping of projecting CBFN by low-affinity neurotrophin receptor p75 (p75NTR ) staining and (iv) the double fluorescence labeling of ChAT and the neuronal markers p75NTR, nitric oxide synthase (NOS), calbindin, calretinin, parvalbumin, tyrosine hydroxylase and substance P. While cholinergic interneurons were found in the hippocampus, they were not detectable in the neocortex. CBFN were shown to abundantly co-express p75NTR, except in the substantia innominata and ventral pallidum. Whereas cholinergic neurons were devoid of most investigated markers, a subset also contained calbindin or NOS. The selective in vivo labeling of CBFN was achieved with intracerebroventricularly (i.c.v.) injected carbocyanine 3-conjugated ME20.4IgG that recognizes an extracellular epitope of p75NTR. Parallel experiments revealed that the i.c.v. injection of ME20.4IgG-saporin conjugates led to the specific immunolesion of cholinergic cells in about one week, whereas long-term effects of the immunotoxin remain to be further elucidated.

Related Products: ME20.4-SAP (Cat. #IT-15)

Turchi JN, Saunders RC, Mishkin M (2002) Effects of cholinergic deafferentation of rhinal cortex on visual recognition in monkeys. Neuroscience 2002 Abstracts 82.5. Society for Neuroscience, Orlando, FL.

Summary: Excitotoxic lesions of the rhinal (perirhinal/entorhinal) cortices yield substantial deficits in visual recognition (Baxter and Murray, 2001; Malkova et al., 2001). To evaluate the mnemonic role of cholinergic inputs to this region, we compared the visual recognition performance of untreated monkeys with that of monkeys given rhinal cortex infusions of the selective cholinergic immunotoxin ME20.4-SAP. This toxin binds to the p75 receptor, borne by corticopetal cholinergic neurons of the basal forebrain, and is retrogradely transported to the cell body where it permanently destroys ribosomal function. Both groups were first trained to criterion in the rule for delayed nonmatching-to-sample (DNMS) with trial-unique stimuli at a 10-s delay in a Wisconsin General Testing Apparatus. This was followed by treatment and recovery for the experimental group (n=3) and an equivalent rest period for the control group (n=4), after which both groups were retrained on the DNMS rule and then given a memory performance test with increasing delays (30, 60, and 120 s) and list lengths (3, 5, 10, and 20 stimuli). The experimental group relearned the DNMS rule without significant impairment but then demonstrated robust deficits when tested with increasing delays (a mean of 83% vs 95% for controls) and list lengths (67% vs 86% for controls). The findings complement results obtained in a study of muscarinic receptor blockade in the perirhinal cortex (Tang et al., 1997) and indicate that cholinergic integrity of the rhinal cortex is critical for visual recognition memory.

Related Products: ME20.4-SAP (Cat. #IT-15)