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Newton S Canteras

Publications and source records attributed to Newton S Canteras.

14 recordsLinked to original sources
PubMed2007

Pre-training to find a hidden platform in the Morris water maze can compensate for a deficit to find a cued platform in a rat model of Parkinson's disease.

The bilateral intranigral infusion of 1 micromol 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in adult male Wistar rats caused a specific and partial loss of substantia nigra pars compacta (SNc) dopamine neurons, a partial depletion of striatal dopamine, and a deficit to learn the intra-maze cued version of the Morris water maze. Pre-training the SNc rats in the spatial version of the water maze or simply maintaining the animals on the water maze platform reversed this deficit. This improvement was even observed when the order of the extra-maze cues presented to the rats during pre-training of the spatial version was changed during training of the intra-maze cued version. However, this deficit was not reversed either by maintaining the animals on the platform if the spatial cues were surrounded and covered with a curtain or by swimming sessions in the maze without the escape platform and the curtain. These findings suggest that none of the following elements alone, learned during the spatial task pre-training, could help SNc rats learn the intra-maze cued task: improvement of swimming skills or knowledge of the existence of the escape platform; distance between the platform and the border of the pool; location of a particular extra-maze cue; relations among extra-maze cues. However, the simultaneous presence of the escape platform and extra-maze cues (irrespective of their relational configuration) during the pre-training sessions proved to be necessary for this improving effect to occur.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed2006

Periaqueductal gray cholecystokinin infusions block morphine-induced disruption of maternal behavior.

Cholecystokinin (CCK) and opiates interaction is critical for maintaining maternal behavior during lactation. Morphine inhibits while CCK restores maternal behavior. Recently we have shown that periaqueductal gray (PAG) is a region critically involved in the opioidergic blockade of maternal behavior. A critical level of morphine-induced activation of the rostral lateral PAG is required to inhibit maternal behavior in lactating rats. Since central CCK injections reverted morphine-induced inhibition of maternal behavior, we tested whether this peptide would act similarly in the PAG. This hypothesis was confirmed in experiments showing that morphine's inhibitory effect on maternal responsiveness was blocked by 1.0 and 0.2 nmol CCK injections into the rostral PAG, but not in nearby regions of the mesencephalic reticular nucleus. To test for possible compensatory changes the CCK2 receptor due to morphine treatments the expression of CCK2 receptor mRNA was evaluated in the PAG. PAG CCK2 receptor cDNA amplification revealed no difference in morphine treated animals. These results broaden understanding of the role played by CCK in the PAG. This CCK action might not depend on changes in its receptor.

Animals↗
PubMed2006

The supragenual nucleus: a putative relay station for ascending vestibular signs to head direction cells.

Head direction (HD) cells located in several regions of the brain, including the postsubiculum, retrosplenial cortex, lateral dorsal thalamic nucleus, anterior dorsal thalamic nucleus, and lateral mammillary nucleus, provide a signal of the rat's momentary directional heading. Experimental evidence suggests that vestibular inputs are critical for the maintenance these cells' directional sensitivity. However, it is still unclear how vestibular information is conveyed to the HD cell-related circuitry. In a recent study, the supragenual nucleus (SG) was suggested as a putative relay of vestibular inputs to this circuitry. In the present study, using anterograde and retrograde tract-tracing methods, we first investigated whether the SG is in a position to convey vestibular inputs. Next, we examined the projections of the SG with the Phaseolus vulgaris leucoagglutinin method. Our results indicate that the SG receives direct inputs from the medial vestibular nucleus and projects to elements of the HD cell-related circuitry, providing a massive input to the contralateral dorsal tegmental nucleus and a moderately dense projection to the shell region of the lateral mammillary nucleus. Overall, the present findings serve to clarify how vestibular inputs reach the HD cell-related circuit and point out the SG as an important interface to this end.

Animals↗
PubMed2006

Place learning strategy of substantia nigra pars compacta-lesioned rats.

The substantia nigra pars compacta (SNc) and the dorsal striatum are often considered to be necessary for stimulus-response (S-R) habit learning, whereas the dorsal hippocampus is considered to be necessary for relational (declarative) memory. Spatial learning is a kind of relational learning that occurs when a rat is released from different locations (variable start) in a water maze to find a submerged platform that is kept in a constant location. However, when the rat is always released from the same starting position (constant start), it can learn to find the platform oriented by a fixed configuration of cues, that is, by S-R learning. To test the critical role of the SNc in S-R and relational learning, the authors tested adult male Wistar rats, sham-operated or with a lesion in the SNc, in these 2 versions of the water maze task. The SNc lesion was induced by bilateral intranigral infusion of 0.5 micromol 1-methyl-4-phenyl- 1,2,3,6-tetrahydropyridine. Although the SNc-lesioned rats learned the variable-start version as effectively as sham rats did, they were significantly impaired in learning the constant-start version of the task.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed2005

Projections from the subfornical region of the lateral hypothalamic area.

The L-shaped anterior zone of the lateral hypothalamic area's subfornical region (LHAsfa) is delineated by a pontine nucleus incertus input. Functional evidence suggests that the subfornical region and nucleus incertus modulate foraging and defensive behaviors, although subfornical region connections are poorly understood. A high-resolution Phaseolus vulgaris-leucoagglutinin (PHAL) structural analysis is presented here of the LHAsfa neuron population's overall axonal projection pattern. The strongest LHAsfa targets are in the interbrain and cerebral hemisphere. The former include inputs to anterior hypothalamic nucleus, dorsomedial part of the ventromedial nucleus, and ventral region of the dorsal premammillary nucleus (defensive behavior control system components), and to lateral habenula and dorsal region of the dorsal premammillary nucleus (foraging behavior control system components). The latter include massive inputs to lateral and medial septal nuclei (septo-hippocampal system components), and inputs to bed nuclei of the stria terminalis posterior division related to the defensive behavior system, intercalated amygdalar nucleus (projecting to central amygdalar nucleus), and posterior part of the basomedial amygdalar nucleus. LHAsfa vertical and horizontal limb basic projection patterns are similar, although each preferentially innervates certain terminal fields. Lateral hypothalamic area regions immediately medial, lateral, and caudal to the LHAsfa each generate quite distinct projection patterns. Combined with previous evidence that major sources of LHAsfa neural inputs include the parabrachial nucleus (nociceptive information), defensive and foraging behavior system components, and the septo-hippocampal system, the present results suggest that the LHAsfa helps match adaptive behavioral responses (either defensive or foraging) to current internal motivational status and external environmental conditions.

Animals↗
PubMed2005

Lesions of structures showing FOS expression to cat presentation: effects on responsivity to a Cat, Cat odor, and nonpredator threat.

Exposure of rats to a cat elicits Fos activity in a number of brain areas or structures. Based on hodological relationships of these, Canteras has proposed a medial hypothalamic defense system, with input from several forebrain sites. Both electrolytic and neurotoxic lesions of the dorsal premammillary nucleus, which shows the strongest Fos response to cat exposure, produce striking decrements in a number of defensive behaviors to a cat or to cat odor stimuli, but do not have a major effect on either postshock freezing, or responsivity to the odor of a female in estrus. Neurotoxic lesions of the medial amygdala produce decrements in defensiveness to predator stimuli, particularly odor stimuli, that are consistent with a view of this structure as involved with allomonal cues. While dorsal hippocampal lesions had little effect on responsivity to predator stimuli, neurotoxic lesions of the ventral hippocampus reduced freezing and enhanced a variety of nondefensive behaviors to both cat odor and footshock, with similar reductions in defensiveness during context conditioning tests for cat odor, cat exposure and footshock. These results support the view that the dorsal premammillary nucleus is strongly and selectively involved in control of responsivity to predator stimuli. Structures with important input into the medial hypothalamic defense system appear also to be functionally involved with antipredator defensive behaviors, and these lesion studies may suggest specific hypotheses as to the particular defense functions of different areas.

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PubMed2005

Lesion of the substantia nigra, pars compacta impairs delayed alternation in a Y-maze in rats.

Adult male Wistar rats with bilateral substantia nigra, pars compacta (SNc) lesion induced by intranigral administration of 0.5 mumol 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) were used as a model of early phase Parkinson's disease (PD). This treatment caused loss of dopaminergic cells in the SNc and a partial depletion of striatal dopamine. Animals trained up to 80% correct choices presented significantly worse scores after SNc lesion compared to sham-operated animals and spent almost 6 days to reach this criterion again, while sham-operated animals reached this criterion within about 2 days. When naive animals had their SNc lesioned before training, they scored worse than sham-operated animals and took 18 days to reach the 80% correct choices criterion, while sham-operated controls reached this criterion after only 10 days. These results suggest that lesion of the SNc impairs working memory in rats performing this task, in agreement with the working memory impairment in PD patients reported in clinical studies.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed2004

Modulation of predatory odor processing following lesions to the dorsal premammillary nucleus.

Previous studies have shown that electrolytic lesions of the dorsal premammillary nucleus (PMd) produce robust reductions in responsivity of rats to the presence of a live predator as well as to its odor, suggesting a critical role for the PMd in the modulation of defense. The present study investigated whether disruptions in defensive responding were specific to predators or if they may indicate a more general deficit in responding to pheromonal odors. Sexually naive male rats with bilateral ibotenic acid lesions of the PMd were exposed to the odor of a female rat in estrus as well as to the presence of cat odor, and, a live cat. PMd lesions produced a dramatic reduction in freezing and avoidance to the cat odor; and, reductions in freezing, enhanced activity and risk assessment to cat exposure. However, PMd lesions produced no changes in response to the presentation of the female odorant. These results confirm earlier findings of attenuation in defensiveness following electrolytic PMd lesions while extending these findings to suggest that the reduced defensiveness occurs specifically in response to predatory odors.

Animals↗
PubMed2003

Evidence for the substantia nigra pars compacta as an essential component of a memory system independent of the hippocampal memory system.

The aim of the present study was to test if the nigrostriatal pathway is an essential component for a water maze cued task learning and if it works independently of the hippocampal memory system. This hypothesis was tested using an animal model of Parkinson's disease in which male Wistar rats were lesioned in the substantia nigra pars compacta (SNc) by the intranigral infusion of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), thus causing a partial depletion of striatal dopamine. SNc-lesioned and sham-operated animals were implanted bilaterally with guide cannulae above the dorsal hippocampus in order to be tested after the administration of 0.4 microl 2% lidocaine or saline into this structure. The animals were tested in a spatial or in a cued version of the water maze, memory tasks previously reported to model hippocampal-dependent spatial/relational and striatal-dependent S-R learning, respectively. Hippocampal inactivation, but not SNc lesion, impaired learning and memory in the spatial version of the water maze. An opposite situation was observed with the cued version. No significant interaction was observed between the SNc lesion and hippocampal inactivation conditions affecting scores in the spatial or in the cued version of the water maze. These results suggest that the nigrostriatal pathway is an essential part of the memory system that processes S-R learning and that it works independently of the hippocampal memory system that processes spatial/relational memories.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed2003

A direct projection from superior colliculus to substantia nigra for detecting salient visual events.

Midbrain dopaminergic neurons respond to unexpected and biologically salient events, but little is known about the sensory systems underlying this response. Here we describe, in the rat, a direct projection from a primary visual structure, the midbrain superior colliculus (SC), to the substantia nigra pars compacta (SNc) where direct synaptic contacts are made with both dopaminergic and non-dopaminergic neurons. Complementary electrophysiological data reveal that short-latency visual responses in the SNc are abolished by ipsilateral lesions of the SC and increased by local collicular stimulation. These results show that the tectonigral projection is ideally located to relay short-latency visual information to dopamine-containing regions of the ventral midbrain. We conclude that it is within this afferent sensory circuitry that the critical perceptual discriminations that identify stimuli as both unpredicted and biologically salient are made.

Animals↗
PubMed2003

A role for the periaqueductal grey in opioidergic inhibition of maternal behaviour.

Opiates are known to be involved in the regulation of various events surrounding parturition and lactation, such as maternal behaviour in rats. The onset of this behaviour has been closely linked to opiate action in the medial pre-optic area, where administration of morphine disrupts maternal behaviour during lactation. By combining the use of Fos protein immunohistochemical detection and pharmacological manipulations, in the present paper we show that the periaqueductal grey (PAG) is another region critically involved in the opioidergic blockade of maternal behaviour. According to our observations, a critical level of morphine-induced activation of the rostral lateral PAG appears to be required to inhibit maternal behaviour in lactating rats. This hypothesis was further confirmed in experiments showing that morphine's inhibitory effect on maternal responsiveness was blocked by unilateral naloxone injection into the rostral PAG, but not into nearby regions of the mesencephalic reticular nucleus. Therefore, only a partial inhibition of the opiate's effect on the rostral PAG was needed to block the inhibitory effect of morphine on maternal behaviour. Further studies are needed to ascertain whether the rostral lateral PAG plays a role in the natural onset of maternal behaviour, playing a complementary role to the medial pre-optic area, or merely inhibits maternal behaviour in response to this specific pharmacological challenge. Conversely, the present findings may well reflect a more general role of the PAG, seemingly providing an important piece of information for proposing a hitherto unexplored concept of the PAG as an important centre for the selection of adaptive behavioural responses.

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PubMed2002

The medial hypothalamic defensive system: hodological organization and functional implications.

The hypothalamus is a relatively small division of the vertebrate forebrain that plays especially important roles in neural mechanisms assuring homeostasis, defense, and reproduction. Previous studies from our laboratory have suggested a distinct circuit in the medial hypothalamic zone as critically involved in the organization of innate defensive behavior. Thus, after exposure to a natural predator known to elicit innate defensive responses, increased Fos levels in the medial zone of the hypothalamus have been found restricted to the anterior hypothalamic nucleus, dorsomedial part of the ventromedial nucleus, and dorsal premammillary nucleus (PMd). Previous anatomical studies have shown that these Fos-responsive cell groups in the medial hypothalamus are interconnected in a distinct neural system, in which the PMd appears to be a critical element for the expression of defensive responses elicited by the presence of a predator. The purpose of this review is to provide an overview of what is currently known about the functional and hodological organization of this hypothalamic circuit subserving defensive responses.

Animals↗
PubMed2002

The lesion of the rat substantia nigra pars compacta dopaminergic neurons as a model for Parkinson's disease memory disabilities.

1. In this article we review the studies of memory disabilities in a rat model of Parkinson's disease (PD). 2. Intranigral administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to rats causes a partial lesion in the substantia nigra, compact part (SNc) and a specific loss of dopamine and its metabolites in the striatum of rats. 3. These animals present learning and memory deficits but no sensorimotor impairments, thus modeling the early phase of PD when cognitive impairments are observed but the motor symptoms of the disease are barely present. 4. The cognitive deficits observed in these animals affect memory tasks proposed to model habit learning (the cued version of the water maze task and the two-way active avoidance task) and working memory (a working memory version of the water maze), but spare long-term spatial memory (the spatial reference version of the Morris water maze). 5. The treatment of these animals with levodopa in a dose that restores the striatal level of dopamine does not reverse these memory impairments, probably because this treatment promotes a high level of dopamine in extrastriatal brain regions, such as the prefrontal cortex and the hippocampus. 6. On the other hand, the adenosine receptor antagonist, caffeine, partly reverse the memory impairment effect of SNc lesion in these rats. This effect may be due to caffeine action on nigrostriatal neurons, since it induces dopamine release and modulates the interaction between adenosine and dopamine receptor activity. 7. These results suggest that the MPTP SNc-lesioned rats are a good model to study memory disabilities related to PD and that caffeine and other selective A(2A) adenosine receptor antagonists are promising drugs to treat this symptoms in PD patients.

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