sfn2006

Northrop LE, Erskine MS (2006) Noradrenergic nuclei involved in sensory input during mating project to the ventromedial hypothalamus and are involved in mating-induced pseudopregnancy in female rats. Neuroscience 2006 Abstracts 661.23. Society for Neuroscience, Atlanta, GA.

Summary: The ventrolateral region of the ventromedial hypothalamus (VMHvl) is known to control female sexual receptivity through the activity of ovarian steroids in the female rat. These receptors are thought to aide in the steroid-dependent facilitation of the lordosis posture. Besides harboring estrogen and progesterone receptors, dense numbers of noradrenergic receptors are also present in the VMHvl. Previous research has shown that norepinephrine is released in significant amounts within the VMHvl after a female receives vaginocervical stimulation (VCS). At the time of mating, the vaginocervical sensory input travels from the brainstem, through the ventral noradrenergic bundle (VNAB), and finally to the VMH. Sufficient amounts of VCS are necessary for inducing twice daily prolactin surges, which are required for the initiation of pseudopregnancy (PSP). To distinguish whether these cells play a role in mating-induced PSP, they were selectively lesioned using the immunotoxin anti-dopamine-β-hydroxylase-saporin (DBH-SAP) 10 days prior to mating. Females were given bilateral VMHvl infusions of either 60ng/0.6µl of DBH-SAP or 2ng/0.6µl of IGG-SAP (non-specific control). Ten days following infusion on proestrous, females received one of two treatments: no VCS (home cage), or a sufficient amount of VCS (15 intromissions from males) to induce PSP. PSP was measured using vaginal smears and serum PRL concentrations. The next witnessed proestrous day after mating, females were mated again with the same type of stimulus as previously administered and perfused 90 min later. The brainstems were cut in 30µm sections, and ICC was used to visualize DBH and FOS immunoreactivity (IR). FOS-IR and DBH-IR cells were counted in the A2 and A1 cell regions, components of the VNAB. DBH-SAP infused females that received 15I showed 50% induction of PSP whereas IGG-SAP (15I) females showed 100% induction of PSP. None of the home cage rats became PSP . VMHvl DBH-SAP infusions significantly decreased DBH/FOS-IR expression in A2 and A1 nuclei, as well as decreased expression in DBH-IR in A2 nuclei compared to IGG-SAP infused females. Our results show that A1 and A2 noradrenergic cells which innervate the VMHvl are required for initiation of P/PSP.

Related Products: Anti-DBH-SAP (Cat. #IT-03)

Lu J, Yoshida K, Fuller PM, Saper CB (2006) Absence of a systemic febrile response to PGE2 and LPS following targeted saporin lesions of the rostral raphe pallidus. Neuroscience 2006 Abstracts 662.18. Society for Neuroscience, Atlanta, GA.

Summary: Anatomical studies have indicated that the rostral raphe pallidus (RPa) medullary area contains sympathetic premotor neurons that may be required for the fever responses triggered by prostaglandin E2 (PGE2) and lipopolysaccharide (LPS) administration. For example, stimulation of this region increases sympathetic activity to brown adipose tissue (BAT) and arteries of the tail, the two primary thermoregulator effector organ in the rat. In addition, neurons in this region are activated by cold exposure and central administration of PGE2. To better understand the role of the RPa in the systemic febrile response to endogenous and exogenous pyrogenic mediators, we performed targeted orexin-saporin lesions of the RPa. Following lesions of the RPa, the amplitude of core body temperature (Tb), as compared with pre-lesion measurements and controls, was significantly increased (p<0.001). Mean Tb did not differ between groups, however. In addition, fever responses to both i.p. LPS and i.c.v. PGE2 were completely blocked in the RPa lesioned rats. Importantly, following LPS administration, the RPa lesioned animals demonstrated the same pattern of Fos expression in the preoptic area as compared to intact controls, suggesting normal activation of the pyrogen-reception system. These observations establish a critical role for the RPa nucleus in the systemic fever response to the pyrogenic mediators LPS and PGE2.

Related Products: Orexin-B-SAP (Cat. #IT-20)

Torner EK, Flesher MM, Chavez CM, Linton KD, Herbert MS, Butt AE (2006) 192 IgG-saporin lesions of the cholinergic basal forebrain disrupt attention and awareness in Pavlovian trace but not delay conditioning in rats. Neuroscience 2006 Abstracts 667.19. Society for Neuroscience, Atlanta, GA.

Summary: Recent research suggests that Pavlovian trace conditioning, but not delay conditioning, requires awareness or attention, where these processes appear to depend on specific brain systems. For example, past research has shown that although amnesiac humans with damage to the hippocampus (HPC) acquire a normal conditioned response (CR) in delay conditioning paradigms where the conditioned stimulus (CS) and unconditioned stimulus (US) partly overlap, they fail to acquire the CR in trace conditioning paradigms where the CS and US are separated in time. Others have shown that the anterior cingulate cortex (ACC) is similarly necessary for trace but not delay conditioning in rats. Another study in rabbits also suggests medial prefrontal cortex (mPFC) involvement in trace but not delay conditioning. The basal forebrain cholinergic system (BFCS) has projections to mPFC, ACC, and HPC. Given that each of these regions is critical for trace but not delay conditioning, we hypothesized that lesions of the BFCS using 192 IgG-saporin (SAP) would selectively impair trace but not delay appetitive conditioning in rats. Rats received bilateral injections of SAP or saline only (sham lesion control group) into BFCS prior to conditioning with a white noise CS and sucrose pellet US in either a delay or 10 s trace conditioning paradigm. Results supported our hypotheses, with the BFCS lesion group showing normal delay conditioning but impaired trace conditioning. In order to assess the potential for distraction to exacerbate the observed BFCS lesion-induced impairments in trace conditioning, a visual distracter (continuously flashing light) was added to the trace conditioning paradigm in a second experiment. Given evidence suggesting BFCS involvement in attention, it was hypothesized that the addition of a visual distracter to the trace conditioning task would cause a greater degree of impairment in the BFCS lesion group than in the control group tested in that task. Preliminary data support this hypothesis. Together, these experiments suggest that the BFCS is necessary for normal trace conditioning, which is argued to require both awareness and working memory. The additional impairment in trace conditioning caused by the visual distracter further suggests a role for the BFCS in mediating attention.

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

Van Kampen JM, Eckman CB (2006) Cholinergic agonists restore deficits in hippocampal neurogenesis after basal forebrain lesions in the adult rat brain. Neuroscience 2006 Abstracts 674.13. Society for Neuroscience, Atlanta, GA.

Summary: Discrete regions of the adult CNS, including the dentate gyrus of the hippocampus, retain the capacity for neurogenesis. Progenitor cells in these regions may represent a potential source of endogenous cells for replacement therapies in neurodegenerative diseases. In order to facilitate the development of such therapeutic approaches, an understanding of the microenvironmental signals regulating neurogenesis in the adult brain is essential. Small molecule neurotransmitters, such as acetylcholine, have been shown to regulate neurogenesis both during development and in the adult brain. In the studies presented here, we examine the effects of various cholinergic agonists on hippocampal neurogenesis in the adult rat brain. Intraventricular administration of a nicotinic agonist significantly attenuated proliferation, while muscarinic agonists triggered a dose-dependent increase in neurogenesis within the dentate gyrus and CA1 regions of the hippocampus. This effect was blocked by the M1 receptor-selective antagonist, pirenzepine. The basal forebrain provides an abundant source of cholinergic input to the hippocampus, thought to play an important role in learning and memory and Alzheimer’s disease (AD) pathophysiology. Loss of this cholinergic innervation, as occurs in AD, was achieved by a selective immunotoxin and resulted in a significant reduction in hippocampal neurogenesis. This loss of neurogenesis was reversed by intraventricular administration of a muscarinic receptor agonist. The loss of basal forebrain cholinergic inputs observed in AD may contribute to deficits in learning and memory through reductions in hippocampal neurogenesis. The results reported here suggest that pharmacological manipulation of the cholinergic system may represent a means of stimulating hippocampal neurogenesis as a potential treatment strategy.

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

Sengelaub DR, Osborne MC, Little CM, Huyck KD, Verhovshek T (2006) Neuroprotective effects of testosterone in two models of spinal motoneuron injury. Neuroscience 2006 Abstracts 683.12. Society for Neuroscience, Atlanta, GA.

Summary: Following induced death or axotomy of spinal motoneurons remaining motoneurons atrophy, but this atrophy can be reversed or prevented by treatment with testosterone (T). For example, partial depletion of motoneurons from the highly androgen-sensitive spinal nucleus of the bulbocavernosus (SNB) induces dendritic atrophy in remaining motoneurons, and this atrophy is prevented by treatment with T. To test whether T has similar effects in more typical motoneurons, we examined potential neuroprotective effects in motoneurons innervating muscles of the quadriceps. Motoneurons innervating the vastus medialis muscle were selectively killed by intramuscular injection of cholera toxin conjugated saporin. Simultaneously, some saporin-injected rats were given implants containing T or left untreated. Four weeks later, motoneurons innervating the ipsilateral vastus lateralis muscle were labeled with cholera toxin conjugated HRP, and dendritic arbors were reconstructed in 3 dimensions. Compared to intact control males, partial motoneuron depletion resulted in decreased dendritic length (70%) and soma size (13%) in remaining quadriceps motoneurons, but as in the SNB, this atrophy was attenuated by T treatment. In a second model, brain-derived neurotrophic factor (BDNF) and T have a combinatorial effect in the maintenance of motoneurons after axotomy in that dendritic morphology is supported by BDNF treatment, but only in the presence of T. Using immunohistochemical methods, we examined the regulation of the expression of the BDNF receptor, trkB, by T. In both the highly androgen-sensitive motoneurons of the SNB and the more typical quadriceps motoneurons, the expression of trkB receptors was regulated by the presence of T. Motoneurons of castrated animals deprived of T show reduced expression of trkB receptors compared to motoneurons of intact animals or castrated animals given T replacement. This finding suggests that maintenance of trkB receptors with T may be necessary to permit the trophic effects of BDNF in supporting dendritic morphology after axotomy. Together, these findings suggest that T regulates neuroprotective effects through a variety of mechanisms, not only in highly androgen-sensitive motoneurons, but in more typical motoneuron populations as well.

Related Products: CTB-SAP (Cat. #IT-14)

Farias P, Valdes J, Riveros M, Torrealba F (2006) The tuberomammillary nucleus is a key component of the arousal system for the appetitive phase of feeding. Neuroscience 2006 Abstracts 361.24. Society for Neuroscience, Atlanta, GA.

Summary: The histaminergic neurons from the tuberomammilary nucleus (TMN) are important in maintaining a high level of arousal or increased sensory alertness. We have seen TMN activation (assessed by Fos-ir) in three different motivated behaviors: feeding, drinking and sexual. The aim of this work is to prove that TMN neurons are essential to promote the arousal during the appetitive phase of feeding. We evaluated the effect of TMN lesion performed with the neurotoxin-saporin coupled to orexin-B on locomotor activity and on thermal responses during food presentation to hungry rats as well as changes in Fos-ir of arousal nuclei and subcortical regions involved in thermal responses. Rats were implanted with telemetric transponders to measure locomotor activity and body core temperature. The brains were processed for Fos-ir, and counterstained with appropriate antibodies to identify ascending arousal system (AAS) nuclei. Histaminergic neurons in the TMN were identified by adenosine deaminase (ADA)-ir. The lesions significantly decreased the number of ADA ir/mm2. The larger lesion (<54% surviving neurons) produced a significant decreased in locomotion and temperature responses to food enticing, compared to intact rats or rats with smaller lesion. Larger lesion abolished the increase in Fos-ir of the AAS nuclei (except the locus coeruleus), and the increase in Fos-ir in thermoregulatory nuclei observed in intact rats. The activation of the orexin neurons of the lateral hypothalamic area and the increase in locomotor activity during food presentation were correlated with the activation of the dorsal TMN. The increased Fos-ir in locus coeruleus and dorsal raphe, and the increase in body core temperature were correlated with the activation of the ventral TMN. In conclusion the TMN neurons seems to act as a “master switch” since they are necessary to initiate the increased arousal that characterizes motivated behaviors, and they likely engage other arousal nuclei as well as thermoregulatory nuclei during the appetitive phase of feeding.

Related Products: Orexin-B-SAP (Cat. #IT-20)

Kozak R, Brown HD, Bruno JP, Sarter M (2006) Prefrontal cholinergic modulation of attentional performance-associated increases in posterior parietal acetylcholine release. Neuroscience 2006 Abstracts 369.15. Society for Neuroscience, Atlanta, GA.

Summary: Increases in medial prefrontal cortex (mPFC) cholinergic activity were demonstrated to mediate attentional performance, particularly under conditions that require increases in attentional effort such as coping with the detrimental performance effects of distractors. Activation of the mPFC, in part as a result of cholinergic activity, is thought to orchestrate top-down effects for optimization of input processing elsewhere in the cortex. The cholinergic inputs to posterior cortical regions have been conceptualized as a branch of the PFC efferent circuitry mediating such top-down effects. Therefore, cholinergic inputs to the mPFC are expected to modulate performance-associated activation of cholinergic projections to the posterior parietal cortex (PPC). Furthermore, the mPFC modulatory influence should be particularly robust in response to performance challenges. This hypothesis was tested by assessing attentional performance-associated ACh release in the PPC in rats after removal of cholinergic inputs to the mPFC. Attentional task-performing animals were equipped with a guide cannula for insertion of a microdialysis probe into the PPC. Cholinergic projections to the mPFC and medial cingulate region were lesioned bilaterally by infusing 192-IgG saporin into the mPFC. Standard task performance of intact rats increased PPC ACh release by ~100% (over baseline).While lesioned animals’ standard task performance was mildly but significantly impaired, performance-associated increases in PPC ACh release in lesioned animals were higher than those observed in intact rats (150-200% over baseline). Presentation of the distractor impaired the performance of intact animals; the lesion exaggerated the detrimental effects of the distractor. In both intact and lesion animals, distractor performance-associated increases in PPC ACh release were higher than the increases observed during standard task performance. However, while peak ACh levels were observed immediately after distractor onset in intact rats, PPC ACh release in lesioned animals increased toward the end of the session, peaking 16 min after distractor termination. These data support the hypotheses that mPFC cholinergic inputs contribute to the regulation of PPC cholinergic activity, particularly following performance challenges.

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

Norman GJ, Knox DK, Brothers H, Berntson GG (2006) Nucleus basalis magnocellularis cholinergic lesions attenuate approach and approach-avoidance conflict. Neuroscience 2006 Abstracts 369.17. Society for Neuroscience, Atlanta, GA.

Summary: Approach-avoidance conflict is a construct that underlies many behavioral tests that model anxiety. These tests include the elevated plus maze, shock-probe avoidance, and operant suppression. Previous reports have demonstrated that nucleus basalis magnocellularis (NBM) cholinergic lesions attenuate operant suppression induced by aversive stimuli. Furthermore, NBM cholinergic lesions attenuate avoidance behavior induced by predator odor. This suggests that NBM cholinergic lesions impact avoidance behavior during approach-avoidance conflict but the effect of NBM cholinergic lesions on approach behavior has not been evaluated extensively. In this study we attempted to separately evaluate the effect of NBM cholinergic lesions on approach and approach-avoidance conflict. NBM cholinergic lesions were induced using the selective cholinergic immunotoxin 192 IgG saporin. Time required to start consumption of a food reward was used as an index of approach. Time required to start consumption of a food reward in the presence of predator odor (trimethylthiazoline) was used as an index of approach-avoidance conflict. NBM cholinergic lesions attenuated the time required to consume a food reward in the presence and absence of trimethylthiazoline. The methods in the study describe a novel way of indexing approach-avoidance conflict. Furthermore, the results suggest that NBM cholinergic neurons may separately modulate neurobehavioral systems that mediate approach and avoidance.

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

Howe WM, Burk JA (2006) Effects of cholinotoxic and excitotoxic posterior parietal cortical lesions on attention in rats. Neuroscience 2006 Abstracts 369.18. Society for Neuroscience, Atlanta, GA.

Summary: Basal forebrain corticopetal cholinergic neurons are necessary for normal attentional processing. However, the interactions of acetylcholine with processing mediated by particular cortical regions remain unclear. The posterior parietal cortex has been implicated in models of attention, including the ability to attend selectively to target stimuli when distracting stimuli are presented. In the present experiment, rats were trained to perform a two-lever attention task that required discrimination of visual signals and trials when no signal was presented. Animals then received infusions of the cholinotoxin, 192IgG-saporin, the excitotoxin, n-methyl-D-aspartate, or vehicle into the posterior parietal cortex (n=9/group). Postsurgically, rats were tested for 30 sessions in the same task trained before surgery followed by 30 sessions with the houselight flashed one sec prior to a signal or non-signal. Lesions did not differentially affect performance in the task tested immediately following surgery. However, when the houselight was flashed prior to the signal or non-signal, both lesion groups were differentially affected compared to sham-lesioned animals. Sham-lesioned animals showed a decrease in the latency to press a lever following lever extension when the houselight was flashed compared to sessions when it was not flashed. However, cholinotoxic lesioned animals did not show this effect. Furthermore, planned comparisons revealed an elevated omission rate for excitotoxic lesioned animals compared to sham-lesioned animals during sessions when the houselight was flashed. The present data support the idea that the posterior parietal cortex and its cholinergic afferents from the basal forebrain are necessary for maintaining attentional performance when task irrelevant stimuli are presented.

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

Farovik A, Brown VJ (2006) Basal forebrain cholinergic lesions impair endogenous covert orienting of attention in the rat. Neuroscience 2006 Abstracts 369.19. Society for Neuroscience, Atlanta, GA.

Summary: The cholinergic system plays an important role in attention, including covert orienting of spatial attention. Covert orienting of attention results in faster reaction times and also fewer errors if attention is directed towards target location by a preceding cue compared to when a cue misdirects attention away from the upcoming target location. This differential effect of the cue on performance is called the ‘validity effect’ (Posner, 1980 Q J E P 32:3-25) and it reflects the benefit of directed attention and the cost of needing to redirect attention from one location to another. Covert orienting can be exogenously cued (e.g., a visual event) or endogenously cued (e.g., a ‘cognitive’ cue indicating the probable target location). In the rat, covert orienting has been demonstrated using exogenous cues, but not, to date, endogenous cues. We used a reaction time task to examine the effects of basal forebrain cholinergic lesions on endogenously cued covert attention. Rats made a directional (left or right) response according to the spatial location (left or right) of target. The probable location of the target varied as a function time, such at shorter foreperiods, there was a greater probability of a left target while at longer foreperiods, right targets were more probable. Reaction time was linearly related to the a priori target probability, reflecting directed attention. Eleven rats received bilateral injections of the selective immunotoxin 192-IgG saporin (0.25µg/µl) into the basal forebrain at coordinates AP – 0.7 ML ± 2.9 DV – 6.7 (from dura). Eleven control rats received injections of vehicle. Overall, the lesion did not impair accuracy of performance, however, the reaction times no longer reflected attentional orienting in lesioned animals. Lesioned animals continued to show delay-dependent speeding prior to the target similar to controls, suggesting that changes in reaction times were not due to effects on motor readiness. We conclude that endogenous attentional orienting reflects a different, and independent, process from that of response preparation and that normal cholinergic function is required for the former but not the latter.

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