Enrique Lanuza

The pallial amygdala of amniote vertebrates: evolution of the concept, evolution of the structure

Embryological studies indicate that the amygdala includes pallial structures, namely the cortical amygdala (olfactory and vomeronasal) and the basolateral complex deep to it. In squamate reptiles, the cortical amygdala includes secondary olfactory (the ventral anterior amygdala) and vomeronasal centres (the nucleus sphericus). In birds, the situation is far less clear, due to the relative underdevelopment of the chemosensory systems. The basolateral amygdala of squamate reptiles includes two ventropallial structures: the posterior dorsal ventricular ridge and the lateral amygdala. Like their mammalian counterparts, these centres give rise to glutamatergic projections to the striatal (centromedial) amygdala and the ventromedial hypothalamus. Using the same criteria, the caudal neostriatum and the ventral intermediate archistriatum may represent the ventral pallial amygdala of birds. The basal nucleus of the mammalian amygdala is a lateropallial territory. In reptiles, the lateral pallium includes the dorsolateral amygdala, which, like the mammalian basal nucleus, projects bilaterally to the striatum/accumbens and receives distinct cholinergic and dopaminergic innervations. In the avian brain, the same embryological, hodological, and histochemical criteria are met by the area temporo-parieto-occipitalis, the caudolateral neostriatum and the dorsal intermediate archistriatum. Therefore, the projections from these structures to the paleostriatum and the lobus paraolfactorius are amygdalostriatal, rather than corticostriatal connections.

Attraction to sexual pheromones and associated odorants in female mice involves activation of the reward system and basolateral amygdala

Adult female mice are innately attracted to non‐volatile pheromones contained in male‐soiled bedding. In contrast, male‐derived volatiles become attractive if associated with non‐volatile attractive pheromones, which act as unconditioned stimulus in a case of Pavlovian associative learning. In this work, we study the chemoinvestigatory behaviour of female mice towards volatile and non‐volatile chemicals contained in male‐soiled bedding, in combination with the analysis of c‐fos expression induced by such a behaviour to clarify: (i) which chemosensory systems are involved in the detection of the primary attractive non‐volatile pheromone and of the secondarily attractive volatiles; (ii) where in the brain male‐derived non‐volatile and volatile stimuli are associated to induce conditioned attraction for the latter; and (iii) whether investigation of these stimuli activates the cerebral reward system (mesocorticolimbic system including the prefrontal cortex and amygdala), which would support the view that sexual pheromones are reinforcing. The results indicate that non‐volatile pheromones stimulate the vomeronasal system, whereas air‐borne volatiles activate only the olfactory system. Thus, the acquired preference for male‐derived volatiles reveals an olfactory‐vomeronasal associative learning. Moreover, the reward system is differentially activated by the primary pheromones and secondarily attractive odorants. Exploring the primary attractive pheromone activates the basolateral amygdala and the shell of nucleus accumbens but neither the ventral tegmental area nor the orbitofrontal cortex. In contrast, exploring the secondarily attractive male‐derived odorants involves activation of a circuit that includes the basolateral amygdala, prefrontal cortex and ventral tegmental area. Therefore, the basolateral amygdala stands out as the key centre for vomeronasal‐olfactory associative learning.

Unconditioned stimulus pathways to the amygdala: effects of posterior thalamic and cortical lesions on fear conditioning.

Plasticity in the lateral nucleus of the amygdala is thought to be critical for the acquisition of Pavlovian fear conditioning. The pathways that transmit auditory conditioned stimulus information originate in auditory processing regions of the thalamus and cortex, but the pathways mediating transmission of unconditioned stimuli to the amygdala are poorly understood. Recent studies suggest that somatosensory (footshock) unconditioned stimulus information is also relayed in parallel to the lateral nucleus of the amygdala from the thalamus (the posterior intralaminar thalamic complex, PIT) and the cortex (parietal insular cortex). In the present study we reexamined this issue. Our results showed that bilateral electrolytic lesions of the PIT alone blocked fear conditioning, whereas bilateral excitotoxic PIT lesions had no effect. These electrolytic PIT lesions did not affect fear conditioning using a loud noise as unconditioned stimulus, defining the effects of PIT lesions as a disruption of somatosensory as opposed to auditory processing. Finally, we performed combined bilateral excitotoxic lesions of the PIT nuclei and electrolytic lesions of the parietal insular cortex. These, like excitotoxic lesions of PIT alone, had no effect on the acquisition of fear conditioning. Thus, somatosensory regions of the thalamus and cortex may well be important routes of unconditioned stimulus transmission to the amygdala in fear conditioning, but information about the unconditioned somatosensory stimulus is also transmitted from other sources that send fibers through, but do not form essential synapses in, the thalamus en route to the amygdala.

Efferents and Centrifugal Afferents of the Main and Accessory Olfactory Bulbs in the Snake Thamnophis sirtalis

This study reinvestigates the efferent projections of the main and accessory olfactory bulbs and describes for the first time the centrifugal projections to the main and accessory olfactory bulbs in the snake Thamnophis sirtalis, using the intraaxonal transport of the anterograde and retrograde tracer biotinylated dextran amine and the retrograde tracer horseradish peroxidase. The olfactory projection consists of three tracts: the lateral olfactory tract, which projects bilaterally to the lateral cortex and the rostral amygdala, crossing the midline through the stria medullaris-habenular commissure system; the intermediate olfactory tract, which projects ipsilaterally to the olfactory tubercle and contributes to the contralateral projection; and the medial olfactory tract, which projects ipsilaterally to the dorsomedial retrobulbar formation. The vomeronasal projection is formed by a single tract, the accessory olfactory tract, that projects ipsilaterally to the nucleus of the accessory olfactory tract, the medial amygdala and the nucleus sphericus. The centrifugal projections to the main and accessory olfactory bulb are composed of two components: one that arises in areas that receive the olfactory or vomeronasal input (neurons in the olfactory tubercle, retrobulbar formation and lateral cortex project to the main olfactory bulb; and neurons in the nucleus of the accessory olfactory tract, the medial amygdala and the nucleus sphericus project to the accessory olfactory bulb), and another that arises in areas not directly implicated in processing the chemosensory information (the nucleus of the diagonal band of Broca and the dorsal cortex). These data allow the recognition of the general pattern of organization of the reptilian olfactory and vomeronasal systems.

Identification of the reptilian basolateral amygdala: an anatomical investigation of the afferents to the posterior dorsal ventricular ridge of the lizard Podarcis hispanica

The presence of multimodal association in the telencephalon of reptiles has been investigated by tracing the afferent connections to the posterior dorsal ventricular ridge (PDVR) of the lizard Podarcis hispanica. The PDVR receives telencephalic afferents from the lateral (olfactory) and dorsal cortices, and from the three unimodal areas of the anterior dorsal ventricular ridge, in a convergent manner. From the diencephalon, it receives afferents from the dorsomedial anterior and medial posterior thalamic nuclei, and from several hypothalamic nuclei. Brainstem afferents to the PDVR originate in the dorsal interpeduncular nucleus, the nucleus of the lateral lemniscus and parabrachial nucleus.

Differential efferent projections of the anterior, posteroventral, and posterodorsal subdivisions of the medial amygdala in mice

The medial amygdaloid nucleus (Me) is a key structure in the control of sociosexual behavior in mice. It receives direct projections from the main and accessory olfactory bulbs (AOB), as well as an important hormonal input. To better understand its behavioral role, in this work we investigate the structures receiving information from the Me, by analysing the efferent projections from its anterior (MeA), posterodorsal (MePD) and posteroventral (MePV) subdivisions, using anterograde neuronal tracing with biotinylated and tetrametylrhodamine-conjugated dextranamines. The Me is strongly interconnected with the rest of the chemosensory amygdala, but shows only moderate projections to the central nucleus and light projections to the associative nuclei of the basolateral amygdaloid complex. In addition, the MeA originates a strong feedback projection to the deep mitral cell layer of the AOB, whereas the MePV projects to its granule cell layer. The Me (especially the MeA) has also moderate projections to different olfactory structures, including the piriform cortex (Pir). The densest outputs of the Me target the bed nucleus of the stria terminalis (BST) and the hypothalamus. The MeA and MePV project to key structures of the circuit involved in the defensive response against predators (medial posterointermediate BST, anterior hypothalamic area, dorsomedial aspect of the ventromedial hypothalamic nucleus), although less dense projections also innervate reproductive-related nuclei. In contrast, the MePD projects mainly to structures that control reproductive behaviors [medial posteromedial BST, medial preoptic nucleus, and ventrolateral aspect of the ventromedial hypothalamic nucleus], although less dense projections to defensive-related nuclei also exist. These results confirm and extend previous results in other rodents and suggest that the medial amygdala is anatomically and functionally compartmentalized.

Projections from the posterolateral olfactory amygdala to the ventral striatum: neural basis for reinforcing properties of chemical stimuli

BackgroundVertebrates sense chemical stimuli through the olfactory receptor neurons whose axons project to the main olfactory bulb. The main projections of the olfactory bulb are directed to the olfactory cortex and olfactory amygdala (the anterior and posterolateral cortical amygdalae). The posterolateral cortical amygdaloid nucleus mainly projects to other amygdaloid nuclei; other seemingly minor outputs are directed to the ventral striatum, in particular to the olfactory tubercle and the islands of Calleja.ResultsAlthough the olfactory projections have been previously described in the literature, injection of dextran-amines into the rat main olfactory bulb was performed with the aim of delimiting the olfactory tubercle and posterolateral cortical amygdaloid nucleus in our own material. Injection of dextran-amines into the posterolateral cortical amygdaloid nucleus of rats resulted in anterograde labeling in the ventral striatum, in particular in the core of the nucleus accumbens, and in the medial olfactory tubercle including some islands of Calleja and the cell bridges across the ventral pallidum. Injections of Fluoro-Gold into the ventral striatum were performed to allow retrograde confirmation of these projections.ConclusionThe present results extend previous descriptions of the posterolateral cortical amygdaloid nucleus efferent projections, which are mainly directed to the core of the nucleus accumbens and the medial olfactory tubercle. Our data indicate that the projection to the core of the nucleus accumbens arises from layer III; the projection to the olfactory tubercle arises from layer II and is much more robust than previously thought. This latter projection is directed to the medial olfactory tubercle including the corresponding islands of Calleja, an area recently described as critical node for the neural circuit of addiction to some stimulant drugs of abuse.

Amygdalo-hypothalamic projections in the lizard Podarcis hispanica: a combined anterograde and retrograde tracing study.

The cells of origin and terminal fields of the amygdalo‐hypothalamic projections in the lizard Podarcis hispanica were determined by using the anterograde and retrograde transport of the tracers, biotinylated dextran amine and horseradish peroxidase. The resulting labeling indicated that there was a small projection to the preoptic hypothalamus, that arose from the vomeronasal amygdaloid nuclei (nucleus sphericus and nucleus of the accessory olfactory tract), and an important projection to the rest of the hypothalamus, that was formed by three components: medial, lateral, and ventral. The medial projection originated mainly in the dorsal amygdaloid division (posterior dorsal ventricular ridge and lateral amygdala) and also in the centromedial amygdaloid division (medial amygdala and bed nucleus of the stria terminalis). It coursed through the stria terminalis and reached mainly the retrochiasmatic area and the ventromedial hypothalamic nucleus. The lateral projection originated in the cortical amygdaloid division (ventral anterior and ventral posterior amygdala). It coursed via the lateral amygdalofugal tract and terminated in the lateral hypothalamic area and the lateral tuberomammillary area. The ventral projection originated in the centromedial amygdaloid division (in the striato‐amygdaloid transition area), coursed through the ventral peduncle of the lateral forebrain bundle, and reached the lateral posterior hypothalamic nucleus, continuing caudally to the hindbrain.

Afferent and efferent connections of the nucleus sphericus in the snake Thamnophis sirtalis: Convergence of olfactory and vomeronasal information in the lateral cortex and the amygdala

This paper is an account of the afferent and efferent projections of the nucleus sphericus (NS), which is the major secondary vomeronasal structure in the brain of the snake Thamnophis sirtalis. There are four major efferent pathways from the NS: 1) a bilateral projection that courses, surrounding the accessory olfactory tract, and innervates several amygdaloid nuclei (nucleus of the accessory olfactory tract, dorsolateral amygdala, external amygdala, and ventral anterior amygdala), the rostral parts of the dorsal and lateral cortices, and the accessory olfactory bulb; 2) a bilateral projection that courses through the medial forebrain bundle and innervates the olfactostriatum (rostral and ventral striatum); 3) a commissural projection that courses through the anterior commissure and innervates mainly the contralateral NS; and 4) a meager bilateral projection to the lateral hypothalamus. On the other hand, important afferent projections to the NS arise solely in the accessory olfactory bulb, the nucleus of the accessory olfactory tract, and the contralateral NS.

Evolution of the Amygdala in Vertebrates

The main aim of this article is to identify the homologues of the different components of the mammalian amygdala in the cerebral hemispheres of non-mammals using, primarily, a topological/embryological perspective. Thus, we first consider two main divisions of the amygdala of mammals, namely the pallial and subpallial (striatopallidal) amygdala. The pallial amygdala includes derivatives of both the lateral and ventral embryonic pallium that in the adult conform layered, superficial areas usually called cortical amygdala, and deep nuclei that conform the basolateral division of the amygdala plus the amygdalohippocampal area (AHA). The components of the subpallial amygdala are usually grouped in two divisions known as central (central amygdala plus parts of the bed nucleus of the stria terminalis, BST) and medial (medial amygdala plus the posteromedial BST) extended amygdala (EA). We then characterize each of the pallial and subpallial components of the mammalian amygdala using neurochemical and hodological data from the literature. After dissecting out and characterizing the amygdaloid centers of mammals, we use the same criteria (topological/embryological, neurochemical, and hodological) to identify the different components of the reptilian amygdala. This approach reveals that the cortical amygdala of reptiles is composed of the nucleus sphericus and the ventral anterior amygdala, plus maybe portions of the caudal lateral cortex. The reptilian basolateral amygdala includes the posterior dorsal ventricular ridge and the dorsolateral amygdaloid nucleus. In addition, the ventral posterior amygdala seems the reptilian homologue of the mammalian AHA. As in mammals, centers in the subpallial amygdala of reptiles conform a central (striatoamygdaloid transition area and dorsolateral BST) and medial (medial amygdala plus the ventromedial BST) EA. The strong similarities between the avian and reptilian cerebral hemispheres allow us to make a proposal for the identity of the amygdala and its components in the avian telencephalon. This proposal, which nicely fits the embryological/topological, hodological, and neurochemical criteria used to define the divisions of the mammalian amygdala, suggests that the avian amygdala is much larger than previously believed. Whereas in birds the cortical amygdala is reduced to a small rim of olfacto-recipient tissue in the caudal cerebral hemispheres (posterior cortex piriformis plus the surface of the rostral arcopallium), the avian basolateral amygdala consists of the rest of the arcopallium and most of the caudal nidopallium. In addition, the posterior amygdala is the best candidate for the avian homologue of the AHA of mammals. Finally, the nonpallial centers of avian amygdala can also be grouped into a central (SpA and lateral BST) and a medial (nucleus teniae and medial BST) EA. This thorough comparative analysis suggests that the amygdala is an ancient component of the cerebral hemispheres of tetrapods that includes two functional subsystems, namely the central/basolateral and the medial subsystem (which includes the medial EA and the AHA), involved in managing two different, but closely related, functions. The central/basolateral subsystem coordinates innate and learned reactions of fear/anxiety/aversion (through the descending projections of the central EA) or of attraction/reward-directed behaviors (through its projections to the striatum) to virtually any stimulus. The medial subsystem is primarily involved in the coordination of species-specific behavioral responses to chemosensory stimuli (olfactory and vomeronasal) with a strong emotional component, such as reproductive behaviors, defensive/aggressive behaviors to conspecifics (agonistic behaviors), or to predator-derived chemosignals. The deep interconnections of both subsystems explain why reproductive-agonistic behaviors are strongly emotional and might mediate learned emotional responses to many odorants.