Newton Sabino Canteras

Organization of projections from the medial nucleus of the amygdala: a PHAL study in the rat.

The organization of axonal projections from the four recognized parts of the medial amygdalar nucleus (MEA) were characterized with the Phaesolus vulgaris leucoagglutinin (PHAL) method in male rats. The results indicate that the MEA consists of two major divisions, ventral and dorsal, and that the former may also consist of rostral and caudal regions. As a whole, the MEA generates centrifugal projections to several parts of the accessory and main olfactory sensory pathways, and projections to (a) several parts of the intrahippocampal circuit (ventrally); (b) the ventral striatum, ventral pallidum, and bed nuclei of the stria terminalis (BST) in the basal telencephaon; (c) many parts of the hypothalamus; (d) midline and medial parts of the thalamus; and (e) the periaqueductal gray, ventral tegmental area, and midbrain raphé. The dorsal division of the MEA (the posterodorsal part) is characterized by projections to the principal nucleus of the BST, and to the anteroventral periventricular, medial, and central parts of the medial preoptic, and ventral premammillary hypothalamic nuclei. These hypothalamic nuclei project heavily to neuroendocrine and autonomic‐related parts of the hypothalamic periventricular zone. The ventral division of the MEA (the anterodorsal, anteroventral, and posteroventral parts) is characterized by dense projections to the transverse and interfascicular nuclei of the BST, and to the lateral part of the medial preoptic, anterior hypothalamic, and ventromedial hypothalamic nuclei. However, dorsal regions of the ventral division provide rather dense inputs to the medial preoptic region and capsule of the ventromedial nucleus, whereas ventral regions of the ventral division preferentially innervate the anterior hypotha lamic, dorsomeclial, and ventral parts of the ventromedial nuclei. Functional evidence suggests that circuits associated with dorsal regions of the ventral division may deal with reproductive behavior, whereas circuits associated with ventral regions of the ventral division may deal preferentially with agonistic behavior.

Combinatorial amygdalar inputs to hippocampal domains and hypothalamic behavior systems.

The expression of innate reproductive, defensive, and ingestive behaviors appears to be controlled by three sets of medial hypothalamic nuclei, which are modulated by cognitive influences from the cerebral hemispheres, including especially the amygdala and hippocampal formation. PHAL analysis of the rat amygdala indicates that a majority of its cell groups project topographically (a) to hypothalamic behavior systems via direct inputs, and (b) to partly overlapping sets of hypothalamic behavior control systems through inputs to ventral hippocampal functional domains that in turn project to the medial hypothalamus directly, and by way of the lateral septal nucleus. Amygdalar cell groups are in a position to help bias or prioritize the temporal order of instinctive behavior expression controlled by the medial hypothalamus, and the memory of associated events that include an emotional or affective component.

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.

Afferent connections of the subthalamic nucleus: a combined retrograde and anterograde horseradish peroxidase study in the rat.

A comprehensive characterization of the afferent connections of the subthalamic nucleus of Luys (STN) is a necessary step in the unraveling of extrapyramidal mechanisms. In the present study, the STN afferents in the rat were systematically investigated with the aid of retrograde and anterograde horseradish peroxidase tracer techniques. The results indicate that, besides a massive input from the dorsal pallidum, the STN receives substantial projections from several districts of the cerebral cortex (the medial division of the prefrontal cortex, the first motor and primary somatosensory areas, and the granular insular territory), the ventral pallidum, the parafascicular nucleus of the thalamus and the pedunculopontine tegmental nucleus, as well as a modest innervation from the dorsal raphe nucleus. In spite of the fact that many additional structures were found to contain retrogradely labeled neurons after tracer injections in the STN, no other projection to the latter nucleus could be effectively established in our anterograde experimental series.

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.

The many paths to fear

Fear is an emotion that has powerful effects on behaviour and physiology across animal species. It is accepted that the amygdala has a central role in processing fear. However, it is less widely appreciated that distinct amygdala outputs and downstream circuits are involved in different types of fear. Data show that fear of painful stimuli, predators and aggressive members of the same species are processed in independent neural circuits that involve the amygdala and downstream hypothalamic and brainstem circuits. Here, we discuss data supporting multiple fear pathways and the implications of this distributed system for understanding and treating fear.

Fos-like immunoreactivity in the periaqueductal gray of rats exposed to a natural predator

In the present study we examined, in rats exposed to a predator (cat), the distribution of neurons expressing Fos along the continuum formed by the central gray surrounding the caudal pole of the third ventricle and the periaqueductal gray (PAG). After the predatory encounter, a distinct cluster of Fos-immunoreactive cells was observed in the precommissural nucleus. In the rostral two-thirds of the PAG, Fos expression was mostly seen in the dorsomedial and dorsolateral regions. In contrast, at caudal levels of the PAG, most of the Fos-labelled neurons were distributed in the lateral and ventrolateral PAG. These results are discussed and compared with the pattern of the PAG activation after fear conditioned to a context or elicited by aversive foot shock.

Connections of the nucleus incertus.

The nucleus incertus (NI) is a distinct cell group in caudoventral regions of the pontine periventricular gray, adjacent to the ventromedial border of the caudal dorsal tegmental nucleus. Recent interest in the NI stems from evidence that it represents one of the periventricular sites with the highest expression levels of mRNA encoding the type 1 corticotropin‐releasing hormone (CRH) receptor, which has a high affinity for naturally occurring CRH, perhaps accounting for some of the extrapituitary actions of the peptide on autonomic and behavioral components of the stress response. However, almost nothing is known about NI function and hodological relationships. In this paper, we present the results of a systematic analysis of NI inputs and outputs using cholera toxin B subunit as a retrograde tracer and Phaseolus vulgaris‐leucoagglutinin as an anterograde tracer. Our retrograde tracer experiments indicate that the NI is in a strategic position to integrate information related to behavioral planning (from the prefrontal cortex), lateral habenular processing, hippocampal function, and oculomotor control. Based on its efferent connections, the NI is in a position to exert significant modulating influences on prefrontal and hippocampal cortical activity, and the nucleus is also in a position to influence brain sites known to control locomotor behavior, attentive states, and learning processes. Overall, the present results support the idea that the NI is a distinct region of the pontine periventricular gray, and together with the superior central (median raphé) and interpeduncular nuclei the NI appears to form a midline behavior control network of the brainstem. J. Comp. Neurol. 438:86–122, 2001.

Comparison of bilaterally 6-OHDA- and MPTP-lesioned rats as models of the early phase of Parkinson's disease: histological, neurochemical, motor and memory alterations.

This study compares histological, neurochemical, behavioral, motor and cognitive alterations as well as mortality of two models of Parkinsons disease in which 100 microg 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) or 6 microg 6-hydroxydopamine (6-OHDA) was bilaterally infused into the central region of the substantia nigra, compact part, of adult male Wistar rats. Both neurotoxins caused a significant loss of nigral tyrosine hydroxylase-immunostained cells and striatal dopamine depletion, but 6-OHDA caused more widespread and intense cell loss, more intense body weight loss and more mortality than MPTP. Both 6-OHDA- and MPTP-lesioned rats presented similar deficits in performing a working memory and a cued version of the Morris water maze task and few exploratory/motor alterations in the open field and catalepsy tests. However, rats presented a significant and transitory increase in locomotor activity after the MPTP lesion and a hypolocomotor behavior tended to be present after the 6-OHDA lesion. The picture of mild motor effects and robust impairment of habit learning and spatial working memory observed in MPTP-lesioned rats models the early phase of Parkinsons disease.

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.