Relaxin is a potent renal vasodilator in conscious rats.
The kidneys and other nonreproductive organs vasodilate during early gestation; however, the "pregnancy hormones" responsible for the profound vasodilation of the renal circulation during pregnancy are unknown. We hypothesized that the ovarian hormone relaxin (RLX) contributes. Therefore, we tested whether the administration of RLX elicits renal vasodilation and hyperfiltration in conscious adult, intact female rats. After several days of treatment with either purified porcine RLX or recombinant human RLX 2 (rhRLX), effective renal plasma flow (ERPF) and glomerular filtration rate (GFR) increased by 20%-40%. Comparable renal vasodilation and hyperfiltration was also observed in ovariectomized rats, suggesting that estrogen and progesterone are unnecessary for the renal response to rhRLX. The nitric oxide synthase inhibitor Nomega-nitro-L-arginine methyl ester completely abrogated the increase in ERPF and GFR elicited by chronic administration of purified porcine RLX. In contrast, the renal vasoconstrictory response to angiotensin II was attenuated by the RLX treatment. Short-term infusion of purified porcine RLX to conscious rats over several hours failed to increase ERPF and GFR. Plasma osmolality was consistently reduced by the chronic administration of both RLX preparations. In conclusion, the renal and osmoregulatory effects of chronic RLX administration to conscious rats resemble the physiological changes of pregnancy in several respects: (a) marked increases in ERPF and GFR with a mediatory role for nitric oxide; (b) attenuation of the renal circulatory response to angiotensin II; and (c) reduction in plasma osmolality. (+info)
Modulation of long-term synaptic depression in visual cortex by acetylcholine and norepinephrine.
In a slice preparation of rat visual cortex, we discovered that paired-pulse stimulation (PPS) elicits a form of homosynaptic long-term depression (LTD) in the superficial layers when carbachol (CCh) or norepinephrine (NE) is applied concurrently. PPS by itself, or CCh and NE in the absence of synaptic stimulation, produced no lasting change. The LTD induced by PPS in the presence of NE or CCh is of comparable magnitude with that obtained with prolonged low-frequency stimulation (LFS) but requires far fewer stimulation pulses (40 vs 900). The cholinergic facilitation of LTD was blocked by atropine and pirenzepine, suggesting involvement of M1 receptors. The noradrenergic facilitation of LTD was blocked by urapidil and was mimicked by methoxamine, suggesting involvement of alpha1 receptors. beta receptor agonists and antagonists were without effect. Induction of LTD by PPS was inhibited by NMDA receptor blockers (completely in the case of NE; partially in the case of CCh), suggesting that one action of the modulators is to control the gain of NMDA receptor-dependent homosynaptic LTD in visual cortex. We propose that this is a mechanism by which cholinergic and noradrenergic inputs to the neocortex modulate naturally occurring receptive field plasticity. (+info)
Neural encoding in orbitofrontal cortex and basolateral amygdala during olfactory discrimination learning.
Orbitofrontal cortex (OFC) is part of a network of structures involved in adaptive behavior and decision making. Interconnections between OFC and basolateral amygdala (ABL) may be critical for encoding the motivational significance of stimuli used to guide behavior. Indeed, much research indicates that neurons in OFC and ABL fire selectively to cues based on their associative significance. In the current study recordings were made in each region within a behavioral paradigm that allowed comparison of the development of associative encoding over the course of learning. In each recording session, rats were presented with novel odors that were informative about the outcome of making a response and had to learn to withhold a response after sampling an odor that signaled a negative outcome. In some cases, reversal training was performed in the same session as the initial learning. Ninety-six of the 328 neurons recorded in OFC and 60 of the 229 neurons recorded in ABL exhibited selective activity during evaluation of the odor cues after learning had occurred. A substantial proportion of those neurons in ABL developed selective activity very early in training, and many reversed selectivity rapidly after reversal. In contrast, those neurons in OFC rarely exhibited selective activity during odor evaluation before the rats reached the criterion for learning, and far fewer reversed selectivity after reversal. The findings support a model in which ABL encodes the motivational significance of cues and OFC uses this information in the selection and execution of an appropriate behavioral strategy. (+info)
Complete compensation in skilled reaching success with associated impairments in limb synergies, after dorsal column lesion in the rat.
Each of the dorsal columns of the rat spinal cord conveys primary sensory information, by way of the medullary dorsal column nucleus, to the ventrobasal thalamus on the contralateral side; thus the dorsal columns are an important source of neural input to the sensorimotor cortex. Damage to the dorsal columns causes impairments in synergistic proximal or whole-body movements in cats and distal limb impairments in primates, particularly in multiarticulated finger movements and tactile foviation while handling objects, but the behavioral effects of afferent fiber lesions in the dorsal columns of rodents have not been described. Female Long-Evans rats were trained to reach with a forelimb for food pellets and subsequently received lesions of the dorsomedial spinal cord at the C2 level, ipsilateral to their preferred limb. Reaching success completely recovered within a few days of dorsal column lesion. Nevertheless, a detailed analysis of high-speed video recordings revealed that rotatory limb movements (aiming, pronation, supination, etc.) were irreversibly impaired. Compensation was achieved with whole-body and alternate limb movements. These results indicate the following: (1) in the absence of the dorsal columns, other sensorimotor pathways support endpoint success in reaching; (2) sensory input conveyed by the dorsal columns is important for both proximal and distal limb movements used for skilled reaching; and (3) detailed behavioral analyses in addition to endpoint measures are necessary to completely describe the effects of dorsal column lesions. (+info)
Response of hippocampal synapses to natural stimulation patterns.
We have studied the synaptic responses in hippocampal slices to stimulus patterns derived from in vivo recordings of place cell firing in a behaving rodent. We find that synaptic strength is strongly modulated during the presentation of these natural stimulus trains, varying 2-fold or more because of short-term plasticity. This modulation of synaptic strength is precise and deterministic, because the pattern of synaptic response amplitudes is nearly identical from one presentation of the train to the next. The mechanism of synaptic modulation is primarily a change in release probability rather than a change in the size of the elementary postsynaptic response. In addition, natural stimulus trains are effective in inducing long-term potentiation (LTP). We conclude that short-term synaptic plasticity--facilitation, augmentation, and depression--plays a prominent role in normal synaptic function. (+info)
Embryonic and postnatal injections of bromodeoxyuridine produce age-dependent morphological and behavioral abnormalities.
The mitotic marker 5-bromodeoxyuridine (BrdU) was injected twice daily (60 mg/kg) into pregnant hooded rats on one of embryonic days (E) 11, 12, 13, 15, 17, or 21, or into rat pups on postnatal day (P) 10. The principal findings were the following: (1) BrdU exposure on E11 produces profound effects on body morphology, and animals must be fed a special diet because of chronic tooth abnormalities; (2) BrdU exposure at E17 or earlier produces a change in coat spotting pattern, the precise pattern varying with age; (3) BrdU exposure on E15 or earlier produces a reduction in both brain and body weight; (4) BrdU exposure on E17 or earlier reduces cortical thickness; (5) BrdU exposure on E11-E13 and at P10 reduces cerebellar size relative to cerebral size; (6) spatial learning is significantly affected after injections of BrdU at E11-E17, but the largest effect is on E17; (7) the deficit in spatial learning may be related in part to a reduction in visual acuity; and (8) skilled forelimb ability is most disrupted after BrdU exposure at E15 but is also impaired after injections on E13 or earlier. BrdU thus has teratological effects on body, brain, and behavior that vary with the developmental age of the fetus or infant. (+info)
Role of the CNS melanocortin system in the response to overfeeding.
The voluntary suppression of food intake that accompanies involuntary overfeeding is an effective regulatory response to positive energy balance. Because the pro-opiomelanocortin (POMC)-derived melanocortin system in the hypothalamus promotes anorexia and weight loss and is an important mediator of energy regulation, we hypothesized that it may contribute to the hypophagic response to overfeeding. Two groups of rats were overfed to 105 and 116% of control body weight via a gastric catheter. In the first group, in situ hybridization was used to measure POMC gene expression in the rostral arcuate (ARC). Overfeeding increased POMC mRNA in the ARC by 180% relative to levels in control rats. For rats in the second group, the overfeeding was stopped, and they were infused intracerebroventricularly with SHU9119 (SHU), a melanocortin (MC) antagonist at the MC3 and MC4 receptor, or vehicle. Although SHU (0.1 nmol) had no effect on food intake of control rats, intake of overfed rats increased by 265% relative to CSF-treated controls. This complete reversal of regulatory hypophagia not only maintained but actually increased the already elevated weight of overfed rats, whereas CSF-treated overfed rats lost weight. These results indicate that CNS MCs mediate hypophagic signaling in response to involuntary overfeeding and support the hypothesis that MCs are important in the central control of energy homeostasis. (+info)
Pilocarpine toxicity in retinal ganglion cells.
PURPOSE: Muscarinic agents reduce intraocular pressure by enhancing aqueous outflow, probably by stimulating ciliary muscle contraction. However, pilocarpine is a well characterized neurotoxin and is widely used to generate animal seizure models. It was therefore investigated whether pilocarpine was also toxic to retinal ganglion cells. METHODS: Dissociated whole retinal preparations were prepared from postnatal day 16 to 19 rats. Retinal ganglion cells had been previously back-labeled with a fluorescent tracer. Retinal cells were incubated with pilocarpine, lithium, and inositol derivatives, and viability of the retrogradely labeled retinal ganglion cells was assayed after 24 hours. RESULTS: Pilocarpine was toxic to retinal ganglion cells in a dose-dependent fashion. This toxicity was potentiated by lithium and blocked by epi- and myo-inositol. CONCLUSIONS: Pilocarpine is toxic to retinal ganglion cells in a mixed culture assay. This toxicity appears to depend on the inositol pathway and is similar to its mode of action in other neurons. However, 0.4 mM pilocarpine (the lowest concentration that did not affect ganglion cell survival) is roughly 1000-fold higher than the vitreal concentration and 20-fold higher than the scleral concentration that can be obtained with topical administration of 2% pilocarpine in the rabbit eye. (+info)