Glutamate and opioid antagonists modulate dopamine levels evoked by innately attractive male chemosignals in the nucleus accumbens of female rats

Sexual chemosignals detected by vomeronasal and olfactory systems mediate intersexual attraction in rodents, and act as a natural reinforcer to them. The mesolimbic pathway processes natural rewards, and the nucleus accumbens receives olfactory information via glutamatergic projections from the amygdala. Thus, the aim of this study was to investigate the involvement of the mesolimbic pathway in the attraction toward sexual chemosignals. Our data show that female rats with no previous experience with males or their chemosignals display an innate preference for male-soiled bedding. Focal administration of the opioid antagonist b-funaltrexamine into the posterior ventral tegmental area does no…

Attraction to male pheromones and sexual behaviour show different regulatory mechanisms in female mice.

In rodents, female sexual behaviour is under hormonal control. The attraction females show for male-derived nonvolatile chemicals (pheromones) can be regarded as the first step of this behaviour, but it is unknown whether this attraction is also modulated by sexual steroids. To test this possibility, ovariectomized adult female mice with no experience of chemical signals from adult males were randomly assigned to four groups that received oil (control), progesterone, estradiol (E) or estradiol+progesterone (E+P) injections, respectively. Females were then tested for their attraction to male-soiled bedding and, subsequently, for their proceptive behaviour when confronted to adult males. Fema…

Fiber Connections of the Amygdaloid Formation of the Lizard <i>Podarcis hispanica</i>

The amygdaloid formation of the lizard Podarcis hispanica can be divided into three main groups of nuclei on the basis of their input from the main and accessory olfactory bulbs: the vomeronasal amygdala, the olfactory amygdala and the dorsal amygdaloid group, the latter group receiving afferents from neither the main (MOB) or the accessory olfactory bulb (AOB). The vomeronasal amygdala has a centrifugal projection to the AOB, an important commissural connection to the contralateral vomeronasal amygdala, a minor projection to nucleus accumbens, and a bilateral projection to the lateral cortex. The olfactory amygdala displays a bilateral afferents from the MOB, receives a contralateral affer…

The maternal hormone in the male brain: Sexually dimorphic distribution of prolactin signalling in the mouse brain.

Research of the central actions of prolactin is highly focused on females, but this hormone has also documented roles in male physiology and behaviour. Here, we provide the first description of the pattern of prolactin-derived signalling in the male mouse brain, employing the immunostaining of phosphorylated signal transducer and activator of transcription 5 (pSTAT5) after exogenous prolactin administration. Next, we explore possible sexually dimorphic differences by comparing pSTAT5 immunoreactivity in prolactin-supplemented males and females. We also assess the role of testosterone in the regulation of central prolactin signalling in males by comparing intact with castrated prolactin-supp…

Intraspecific Communication Through Chemical Signals in Female Mice: Reinforcing Properties of Involatile Male Sexual Pheromones

In rodents, social and reproductive behaviors critically depend on chemical signals, including sexual pheromones that have been suggested (but not demonstrated) to be rewarding. In this work, we analyze this issue by studying the chemoinvestigatory behavior of adult female mice (without experience with male-derived chemicals) toward 1) the synthetic odorant citralva, 2) bedding soiled by different conspecifics (females, males, and castrated males), and 3) volatiles derived from bedding soiled by males and castrated males (confronted in 2-choice tests). We also study whether these chemical signals are able to induce conditioned place preference, a reliable test for rewarding properties of st…

Sexual pheromones and the evolution of the reward system of the brain: the chemosensory function of the amygdala.

The amygdala of all tetrapod vertebrates receives direct projections from the main and accessory olfactory bulbs, and the strong similarities in the organization of these projections suggest that they have undergone a very conservative evolution. However, current ideas about the function of the amygdala do not pay sufficient attention to its chemosensory role, but only view it as the core of the emotional brain. In this study, we propose that both roles of the amygdala are intimately linked since the amygdala is actually involved in mediating emotional responses to chemical signals. The amygdala is the only structure in the brain receiving pheromonal information directly from the accessory …

Pregnancy Changes the Response of the Vomeronasal and Olfactory Systems to Pups in Mice

Motherhood entails changes in behavior with increased motivation for pups, induced in part by pregnancy hormones acting upon the brain. This work explores whether this alters sensory processing of pup-derived chemosignals. To do so, we analyse the expression of immediate early genes (IEGs) in the vomeronasal organ (VNO; Egr1) and centers of the olfactory and vomeronasal brain pathways (cFos) in virgin and late-pregnant females exposed to pups, as compared to buttons (socially neutral control). In pup-exposed females, we quantified diverse behaviors including pup retrieval, sniffing, pup-directed attack, nest building and time in nest or on nest, as well as time off nest. Pups induce Egr1 ex…

Afferent and efferent connections of the olfactory bulbs in the lizard Podarcis hispanica.

The connections of the olfactory bulbs of Podarcis hispanica were studied by tract-tracing of injected horseradish peroxidase. Restricted injections into the main olfactory bulb (MOB) resulted in bilateral terminallike labeling in the medial part of the anterior olfactory nucleus (AON) and in the rostral septum, lateral cortex, nucleus of the lateral olfactory tract, and ventrolateral amygdaloid nucleus. Bilateral retrograde labeling was found in the rostral lateral cortex and in the medial and dorsolateral AON. Ipsilaterally the dorsal cortex, nucleus of the diagonal band, lateral preoptic area, and dorsolateral amygdala showed labeled cell bodies. Retrogradely labeled cells were also foun…

Ascending projections from the optic tectum in the lizard Podarcis hispanica.

The ascending projections of the optic tectum, including their cells of origin, have been studied in the lizard Podarcis hispanica by means of a two-step experimental procedure. First, tracers were injected in the tectum to study the anterograde labeling in the forebrain. Second, the cells of origin of these projections have been identified by analyzing the retrograde labeling after tracer injections in the thalamus, hypothalamus, and pretectum. Three main tectal ascending pathways have been described: the dorsal tecto-thalamic tract (dtt), the medial tecto-thalamic tract (mtt), and the ventral tecto-thalamic tract (vtt). The dtt originates in radial cells of layers 5 and 7 and bipolar cell…

Amygdaloid projections to the ventral striatum in mice: direct and indirect chemosensory inputs to the brain reward system

Rodents constitute good models for studying the neural basis of socio-sexual behaviour. Recent findings in mice have revealed the molecular identity of the some pheromonal molecules triggering intersexual attraction. However, the neural pathways mediating this basic socio-sexual behaviour remain elusive. Since previous work indicates that the dopaminergic tegmento-striatal pathway is not involved in pheromone reward, the present report explores alternative pathways linking the vomeronasal system with the tegmento-striatal system (the limbic basal ganglia) by means of tract-tracing experiments studying direct and indirect projections from the chemosensory amygdala to the ventral striato-pall…

Evidence for the plant-specific intercellular transport of the Arabidopsis copper chaperone CCH

Summary Arabidopsis copper chaperone (CCH) belongs to a family of eukaryotic proteins that participates in intracellular copper homeostasis by delivering this metal to the secretory pathway. In this work we show that the CCH protein is mainly located along the vascular bundles of senescing leaves and petioles, as shown by tissue prints and immunohistochemical detection. CCH protein also accumulates in stem sieve elements and is collected in phloem exudates. Accordingly, Arabidopsis CCH is the only member of the metallochaperone family described to function intercellularly to date. Moreover, the CCH protein remains stable when plants are subjected to excess copper that causes a rapid and spe…

Calcium-binding proteins in the dorsal ventricular ridge of the lizardPsammodromus algirus

The aim of the present work was to study further the intrinsic organization of the dorsal ventricular ridge of lizards. For that purpose, the morphology and distribution of cells and fibers containing the calcium-binding proteins calbindin-D28k, parvalbumin, and calretinin were investigated by using immunohistochemical methods. Colocalization of calcium-binding proteins with the neurotransmitter gamma-aminobutyric acid (GABA) was also studied because they are shown to coexist in many areas of the telencephalon where they define distinct subpopulations of GABAergic local circuit neurons. Neurons containing calcium-binding proteins are limited to the anterior part of the dorsal ventricular ri…

Avoidance and contextual learning induced by a kairomone, a pheromone and a common odorant in female CD1 mice

Copyright © 2015 Fortes-Marco, Lanuza, Martínez-García and Agustín-Pavón.

Distribution of corticotropin-releasing factor-immunoreactive neurons in the central nervous system of the domestic chicken and Japanese quail

In birds, as in mammals, corticotropin-releasing factor (CRF) is present in a number of extrahypothalamic brain regions, indicating that CRF may play a role in physiological and behavioral responses other than the control of adrenocorticotropin hormone release by the pituitary. To provide a foundation for investigation of the roles of CRF in the control of avian behavior, the distribution of CRF immunoreactivity was determined throughout the central nervous system of the domestic chicken (Gallus domesticus) and Japanese quail (Coturnix japonica). The distribution of CRF-immunoreactive (-ir) perikarya and fibers in the chicken and quail brain was found to be more extensive than previously re…

Distribution of CGRP-like immunoreactivity in the chick and quail brain

Calcitonin gene-related peptide (CGRP)-containing neurones have been implicated in the transmission of visceral sensory information to the cortex and in the control of arterial blood pressure in mammals. However, little is known about its function in other vertebrates. As a first step toward investigating the function of CGRP in birds, its distribution was studied in the domestic chick and quail brain by means of immunocytochemistry, by using antibodies against rat CGRP. The distribution of CGRP immunoreactivity in the chick and quail central nervous system was found to be similar. CGRP-immunoreactive (CGRPi) perikarya were not present in the telencephalon. In the diencephalon, CGRPi perika…

Chemosensory Function of the Amygdala

The chemosensory amygdala has been traditionally divided into two divisions based on inputs from the main (olfactory amygdala) or accessory (vomeronasal amygdala) olfactory bulbs, supposedly playing different and independent functional roles detecting odors and pheromones, respectively. Recently, there has been increased anatomical evidence of convergence inputs from the main and accessory bulbs in some areas of the amygdala, and this is correlated with functional evidence of interrelationships between the olfactory and the vomeronasal systems. This has lead to the characterization of a third division of the chemosensory amygdala, the mixed chemosensory amygdala, providing a new perspective…

Vomeronasal inputs to the rodent ventral striatum.

Vertebrates sense chemical signals through the olfactory and vomeronasal systems. In squamate reptiles, which possess the largest vomeronasal system of all vertebrates, the accessory olfactory bulb projects to the nucleus sphericus, which in turn projects to a portion of the ventral striatum known as olfactostriatum. Characteristically, the olfactostriatum is innervated by neuropeptide Y, tyrosine hydroxylase and serotonin immunoreactive fibers. In this study, the possibility that a structure similar to the reptilian olfactostriatum might be present in the mammalian brain has been investigated. Injections of dextran-amines have been aimed at the posteromedial cortical amygdaloid nucleus (th…

Striato-amygdaloid transition area lesions reduce the duration of tonic immobility in the lizard Podarcis hispanica.

Neuroanatomical data suggest that the lizard striato-amygdaloid transition area is homologous with the mammalian central amygdala. In order to investigate possible functional similarities, tonic immobility was induced in adult lizards and its duration recorded. Each lizard was then randomly assigned to one of three treatments: (1) bilateral striato-amygdaloid transition area lesions, (2) bilateral dorsal cortex lesions or (3) untreated controls. Three days after trial 1, each lizard was subjected to a second trial and the tonic immobility duration recorded. The mean tonic immobility duration in lizards with striato-amygdaloid transition area lesions was significantly shorter (80.5%; p < 0.0…

Sex pheromones are not always attractive: changes induced by learning and illness in mice

A male-specific major urinary protein named darcin is attractive to female mice, Mus musculus, stimulates a learned attraction to volatile components of a male's urinary odour and induces spatial learning. In this article we show that darcin also induces learned attraction for a previously neutral olfactory stimulus (the odorant isoamyl acetate), acquired by repeated presentation of both stimuli together. We hypothesize that this is a case of olfactory–vomeronasal associative learning, in which darcin acts as the unconditioned reinforcer. However, the presence of darcin is not always attractive to adult female mice. Urine from males parasitized by the nematode Aspiculuris tetraptera has no …

Amygdalostriatal projections in reptiles: A tract-tracing study in the lizardPodarcis hispanica

Whereas the lacertilian anterior dorsal ventricular ridge contains unimodal sensory areas, its posterior part (PDVR) is an associative center that projects to the hypothalamus, thus being comparable to the amygdaloid formation. To further understand the organization of the reptilian cerebral hemispheres, we have used anterograde and retrograde tracing techniques to study the projections from the PDVR and adjoining areas (dorsolateral amygdala, DLA; deep lateral cortex, dLC; nucleus sphericus, NS) to the striatum in the lizard Podarcis hispanica. This information is complemented with a detailed description of the organization of the basal telencephalon of Podarcis. The caudal aspect of the d…

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 (centro…

What is the amygdala? A comparative approach.

Elucidating the genetic susceptibility of hypertension associated microalbuminuria: genome wide scan

Objective: To identify genetic susceptibility variants for hypertension associated microalbuminuria. Methods: The study design was a nested case-control genetic association study. Three hundred and three patients were selected from one prospective cohort recruited in the hypertension clinic of two different hospitals with the objective of identify clinical factors associated with microalbuminuria. All the patients were less than 50y, hypertensive grade I and naïve regarding to the treatment at the time of the recruitment. Cases were those who developed microalbuminuria (UAE>=30 mg/day) during the follow up and controls were those who remained with an UAE less than 30 mg/day. UAE was assesse…

Septal complex of the telencephalon of the lizardPodarcis hispanica. II. afferent connections

The afferent connections to the septal complex were studied in the lizard Podarcis hispanica (Lacertidae) by means of a combination of retrograde and anterograde tracing. The results of these experiments allow us to classify the septal nuclei into three main divisions. The central septal division (anterior, lateral, dorsolateral, ventrolateral, and medial septal nuclei plus the nucleus of the posterior pallial commissure) receives a massive, topographically organized, cortical projection (medial, dorsal, and ventral areas) and widespread afferents from the tuberomammillary hypothalamus and the basal telencephalon. Moreover, it receives discrete projections from the dorsomedial anterior thal…

Neural Substrate to Associate Odorants and Pheromones: Convergence of Projections from the Main and Accessory Olfactory Bulbs in Mice

In rodents olfactory stimuli are essential for socio-sexual behaviour. Volatile stimuli mainly activate the main olfactory system, whereas non-volatile ones, some of them considered as pheromones, activate the accessory olfactory system. Traditionally, it has been considered that the efferent projections of the main and the accessory olfactory bulbs innervate different telencephalic areas. Recent studies performed in rats and mice have challenged this view. In this work we explore in mice, through the use of anterograde tracer injections in the olfactory bulbs, the brain centres where olfactory and vomeronasal information might converge.

Role of the vomeronasal system in intersexual attraction in female mice

Although it is generally accepted that rodents' sociosexual behavior relies mainly on chemosignals, the specific roles played by the vomeronasal and olfactory systems in detecting these signals are presently unclear. This work reports the results of three experiments aimed at clarifying the role of the vomeronasal system on gender recognition and intersexual attraction, by analyzing the effects of lesions of the accessory olfactory bulbs (AOB) in chemically naive female mice. The first experiment demonstrates that lesions of the AOB abolish the preference that females show for male-soiled bedding in tests in which the females can contact the bedding, thus having access to both volatile and …

Brain met-enkephalin immunostaining after subacute and subchronic exposure to benzene

Benzene is used in a wide variety of domestic and occupational activities, and due to its lipophilic nature, it accumulates in lipid-rich tissues like the brain. In this sense, neurotoxic action has long been associated with organic solvent exposure and it has been shown that benzene, injected in a single dose or during a prolongued administration, modifies the content of dopamine, noradrenaline, serotonin and its main metabolite 5-hydroxy indolacetic acid, in several brain regions of the rat, then revealing a stimulating action on brain monoamine synthesis and turnover. However, information concerning neurotoxic action of benzene exposure in vivo on peptidergic neuromodulatory systems is s…

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 behaviour in mice. It receives direct projections from the main and accessory olfactory bulbs, as well as an important hormonal input. To better understand its behavioural 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 nucl…

Refining the dual olfactory hypothesis: Pheromone reward and odour experience

In rodents, sexual advertisement and gender recognition are mostly (if not exclusively) mediated by chemosignals. Specifically, there is ample evidence indicating that female mice are ‘innately’ attracted by male sexual pheromones that have critical non-volatile components and are detected by the vomeronasal organ. These pheromones can only get access to the vomeronasal organ by active pumping mechanisms that require close contact with the source of the stimulus (e.g. urine marks) during chemoinvestigation. We have hypothesised that male sexual pheromones are rewarding to female mice. Indeed, male-soiled bedding can be used as a reinforcer to induce conditioned place preference, provided co…

Synchronized Activity in The Main and Accessory Olfactory Bulbs and Vomeronasal Amygdala Elicited by Chemical Signals in Freely Behaving Mice

AbstractChemosensory processing in mammals involves the olfactory and vomeronasal systems, but how the activity of both circuits is integrated is unknown. In our study, we recorded the electrophysiological activity in the olfactory bulbs and the vomeronasal amygdala in freely behaving mice exploring a battery of neutral and conspecific stimuli. The exploration of stimuli, including a neutral stimulus, induced synchronic activity in the olfactory bulbs characterized by a dominant theta rhythmicity, with specific theta-gamma coupling, distinguishing between vomeronasal and olfactory structures. The correlated activation of the bulbs suggests a coupling between the stimuli internalization in t…

Focal Lesions within the ventral striato-pallidum abolish attraction for male chemosignals in female mice

In rodents, socio-sexual behaviour is largely mediated by chemosensory cues, some of which are rewarding stimuli. Female mice display an innate attraction towards male chemosignals, dependent on the vomeronasal system. This behaviour likely reflects the hedonic value of sexual chemosignals. The anteromedial aspect of the olfactory tubercle, along with its associated islands of Calleja, receives vomeronasal inputs and sexually-dimorphic vasopressinergic innervation. Thus, we hypothesised that this portion of the ventral striato-pallidum, known to be involved in reward processing, might be important for sexual odorant-guided behaviours. In this study, we demonstrate that lesions of this regio…

Corrigendum: Wired for motherhood: induction of maternal care but not maternal aggression in virgin female CD1 mice

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

Abstract Background Vertebrates 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. Results Although the olfactory projections have been previously described in the literature, injection of dextran-amines into the rat main olfactory bulb was performed with …

Retinal ganglion cells projecting to the optic tectum and visual thalamus of lizards.

Retinal ganglion cells projecting to the optic tectum and visual thalamus have been investigated in the lizard, Podarcis hispanica. Injections of biotinylated dextran-amine in the optic tectum reveal seven morphological cell varieties including one displaced ganglion cell type. Injections in the visual thalamus yield similar ganglion cell classes plus four giant ganglion cells, including two displaced ganglion cell types. The present study constitutes the first comparison of tectal versus thalamic ganglion cell types in reptiles. The situation found in lizards is similar to that reported in mammals and birds where some cell types projecting to the thalamus are larger than those projecting t…

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…

The vomeronasal cortex - afferent and efferent projections of the posteromedial cortical nucleus of the amygdala in mice

Most mammals possess a vomeronasal system that detects predominantly chemical signals of biological relevance. Vomeronasal information is relayed to the accessory olfactory bulb (AOB), whose unique cortical target is the posteromedial cortical nucleus of the amygdala. This cortical structure should therefore be considered the primary vomeronasal cortex. In the present work, we describe the afferent and efferent connections of the posteromedial cortical nucleus of the amygdala in female mice, using anterograde (biotinylated dextranamines) and retrograde (Fluorogold) tracers, and zinc selenite as a tracer specific for zinc-enriched (putative glutamatergic) projections. The results show that t…

Afferent and efferent projections of the anterior cortical amygdaloid nucleus in the mouse

The anterior cortical amygdaloid nucleus (ACo) is a chemosensory area of the cortical amygdala that receives afferent projections from both the main and accessory olfactory bulbs. The role of this structure is unknown, partially due to a lack of knowledge of its connectivity. In this work, we describe the pattern of afferent and efferent projections of the ACo by using fluorogold and biotinylated dextranamines as retrograde and anterograde tracers, respectively. The results show that the ACo is reciprocally connected with the olfactory system and basal forebrain, as well as with the chemosensory and basomedial amygdala. In addition, it receives dense projections from the midline and posteri…

Amygdalo-hypothalamic projections in the lizardPodarcis 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 rid…

Identification of the reptilian basolateral amygdala: an anatomical investigation of the afferents to the posterior dorsal ventricular ridge of the lizardPodarcis 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.…

Maternal Motivation: Exploring the Roles of Prolactin and Pup Stimuli

Motherhood entails increased motivation for pups, which become strong reinforcers and guide maternal behaviours. This depends on steroids and lactogens acting on the brain of females during pregnancy and postpartum. Since virgin female mice exposed to pups are nearly spontaneously maternal, the specific roles of endocrine and pup-derived signals in the induction of maternal motivation remain unclear. This work investigates maternal motivation in dams and virgin female mice, using a novel variant of the pup retrieval paradigm, the motivated pup retrieval test. We also analyse the role of prolactin (PRL) and of stimuli derived from a litter of pups and its mother, in the acquisition of matern…

Afferent and Efferent Connections of the Cortex-Amygdala Transition Zone in Mice

The transitional zone between the ventral part of the piriform cortex and the anterior cortical nucleus of the amygdala, named the cortex-amygdala transition zone (CxA), shows two differential features that allow its identification as a particular structure. First, it receives dense cholinergic and dopaminergic innervations as compared to the adjacent piriform cortex and amygdala, and second, it receives projections from the main and accessory olfactory bulbs. In this work we have studied the pattern of afferent and efferent projections of the CxA, which are mainly unknown, by using the retrograde tracer Fluorogold and the anterograde tracer biotinylated dextranamine. The results show that …

Selective dopaminergic lesions of the ventral tegmental area impair preference for sucrose but not for male sexual pheromones in female mice

The role of the meso-accumbens dopaminergic pathway in reward-related behaviours is the subject of intense investigation. In this regard, here we analyse the effects of specific lesions of dopaminergic cells of the ventral tegmental area (VTA) of female mice on two goal-directed behaviours, namely sucrose preference (intake of sucrose solution vs. water) and preference for male sexual pheromones (exploration of male-soiled vs. clean bedding). The results indicate that partial lesions of the VTA that impair neither locomotion nor general exploratory behaviour reduce the preference for sucrose (over a 48-h period) but do not alter the innate attraction that females display for male sexual phe…

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…

Attractive properties of sexual pheromones in mice

Abstract It is generally assumed that chemical signals (sexual pheromones) constitute the primary stimulus for sexual attraction in many mammals. However, it is unclear whether these pheromones are volatile or nonvolatile and which sensory systems are involved in their detection (vomeronasal and/or olfactory). Moreover, it has been demonstrated that experience influences the behavioral response to sexual pheromones and the sensory systems implicated. In order to clarify this issue, the attractive properties of volatile and nonvolatile components of the male-soiled bedding have been analyzed in female mice that had no previous experience with adult male-derived chemical signals (chemically n…

Distribution of calcitonin gene-related peptide-like immunoreactivity in the brain of the lizardPodarcis hispanica

The present work studies the distribution of calcitonin gene-related peptide-immunoreactive (CGRP-li) neurons and fibers in the brain of a reptile, the lizard Podarcis hispanica. CGRP-li perikarya were not present in the telencephalon. In the thalamus, CGRP-li perikarya were restricted to the posteromedial and posterolateral nuclei. In the hypothalamus, CGRP-li cells were found mainly in the supramammillary and mammillary nuclei. In the midbrain and brainstem, CGRP-li cells appeared in the ventral tegmental area, the parabrachial nucleus, and the motor nuclei of the III-VII, IX, X, and XII cranial nerves. Motoneurons of the ventral horn of the spinal cord were also immunoreactive for CGRP. …

Adaptive Function and Brain Evolution

Comparing brains is not a mere intellectual exercise but also helps to understand how the brain enables adaptive behavioral strategies to cope with an ever-changing world and how this complex organ has evolved during the phylogeny. For instance, comparative neurobiology helps understanding the specific features of our species, an issue that attracted scientists since the time of Santiago Ramon y Cajal. Following this tradition, 20 years ago Hans ten Donkelaar and Gerhard Roth started the European Conferences on Comparative Neurobiology (ECCN). This e-book includes some of the contributions to the last meeting, the sixth ECCN (Valencia, Spain; April 22-24 2010), plus selected works by severa…

Motherhood‐induced gene expression in the mouse medial amygdala: Changes induced by pregnancy and lactation but not by pup stimuli

During lactation, adult female mice display aggressive responses toward male intrud-ers, triggered by male- derived chemosensory signals. This aggressive behavior is not shown by pup- sensitized virgin females sharing pup care with dams. The genetic mechanisms underlying the switch from attraction to aggression are unknown. In this work, we investigate the differential gene expression in lactating females ex-pressing maternal aggression compared to pup- sensitized virgin females in the me-dial amygdala (Me), a key neural structure integrating chemosensory and hormonal information. The results showed 197 genes upregulated in dams, including genes encoding hormones such as prolactin, growth h…

Piriform Cortex and Amygdala

Publisher Summary A ventral view of the cerebral hemispheres of mammals shows an array of structures ultimately connected with the olfactory bulbs through the olfactory tracts. This is the basis for the old concept of rhinencephalon, a series of neural centers in the cerebral hemispheres, located ventral to the rhinal fissure, for which an olfactory role was assumed. Although mice lack a conspicuous rhinal fissure, their “rhinencephalon” is well developed. The concept of the rhinencephalon is difficult to sustain nowadays, as it includes neural centers of diverse origin, organization and nature. The rhinencephalon comprises several allocortical areas that constitute the olfactory cortex, de…

Hippocampal dopamine receptors modulate cFos expression in the rat nucleus accumbens evoked by chemical stimulation of the ventral hippocampus

Recently, we have shown that D1 and D2 receptors in the ventral hippocampus (VH) modulate both the locomotor activation and the increase in dopamine (DA) levels in the rat nucleus accumbens (NAc) induced by NMDA stimulation of the VH. In the present study we analyze the possible role of VH D1 and D2 receptors in the modulation of the cFos expression in NAc (core and shell subregions) and in dorsal striatum. This was assessed by immunohistochemical analysis of cFos expression in the rat brains after retro-dialysis application of NMDA (50mM, 10 min) into VH, in absence and in presence of either the D1/D5 receptor antagonist SCH 23390 (100 and 250 microM, 60 min) or the D2 receptor antagonist …

Projections from the medial cortex in the brain of lizards: correlation of anterograde and retrograde transport of horseradish peroxidase with Timm staining

Efferent projections of the medial cortex of the lizards Podarcis hispanica and Gallotia stehlinii were studied by examining the transport of horseradish peroxidase; results were correlated with those from Timm-stained sections. Two efferent systems were found. The first reaches the distal part of the outer plexiform layer in the medial, dorsomedial, and dorsal cortices, i.e., zones that are negative to Timm staining, and possibly originates from horizontal fusiform neurons. The second reaches the Timm-positive zones in the cortex and septum and is topographically arranged: the vertical portion of the intermediate and caudal medial cortex and the entire rostral medial cortex project to the …

Pyramidal and nonpyramidal callosal cells in the striate cortex of the adult rat

The aim of this study has been to determine the neuronal types (pyramidal and nonpyramidal) within the rat's visual cortex, which project through the corpus callosum. To this end, the morphology and laminar distribution of callosal cells have been investigated by combining Diamidino Yellow retrograde tracing with intracellular injection of Lucifer Yellow in slightly fixed tissue slices. The visual callosal projection arises from pyramidal cells of diverse morphology in layers II to VIb, as well as from several modified pyramids located mainly in layers II, IV (star pyramids) and VIb (horizontal or inverted pyramids and related forms of spiny stellate cells). Our results indicate that in rat…

Lesions of the dopaminergic innervation of the nucleus accumbens medial shell delay the generation of preference for sucrose, but not of sexual pheromones

Male sexual pheromones are rewarding stimuli for female mice, able to induce conditioned place preference. To test whether processing these natural reinforcing stimuli depends on the dopaminergic innervation of the nucleus accumbens, as for other natural rewards, we compare the effects of specific lesions of the dopaminergic innervation of the medial shell of the nucleus accumbens on two different appetitive behaviours, ‘pheromone seeking’ and sucrose preferential intake. Female mice, with no previous experience with either adult male chemical stimuli or with sucrose, received injections of 6-hydroxydopamine (or vehicle) in the medial shell of the accumbens. Then, we analyzed their preferen…

Corrigendum: Wired for motherhood: induction of maternal care but not maternal aggression in virgin female CD1 mice

Virgin adult female mice display nearly spontaneous maternal care towards foster pups after a short period of sensitization. This indicates that maternal care is triggered by sensory stimulation provided by the pups and that its onset is largely independent on the physiological events related to gestation, parturition and lactation. Conversely, the factors influencing maternal aggression are poorly understood. In this study, we sought to characterize two models of maternal sensitization in the outbred CD1 strain. To do so, a group of virgin females (godmothers) were exposed to continuous cohabitation with a lactating dam and their pups from the moment of parturition, whereas a second group …

Afferents to the red nucleus in the lizardPodarcis hispanica: Putative pathways for visuomotor integration

The afferents to the red nucleus from visual and nonvisual forebrain centers have been investigated in the lizard Podarcis hispanica by using both retrograde and anterograde transport of tracers. Because the red nucleus constitutes a key structure in the limb premotor system, these sensory afferents probably are involved in visuomotor and other forms of sensorimotor integration. After tracer injections aimed at the red nucleus, retrograde labeling was found in the reticular thalamus, the subthalamus, the nucleus of the posterior commissure, as well as in two retinorecipient nuclei, namely, the ventral lateral and pretectal geniculate nuclei, where labeled cells are especially abundant. Thes…

Evolution of vertebrate survival circuits

Evolution selects those adaptive features that increase reproductive probabilities and facilitate survival. Analysing the brain circuits mediating risk-avoidance (e.g. defense) and those allowing reward-seeking (motivated) behaviours in different vertebrates leads to several main conclusions. First, circuits mediating risk-avoidance are similar in all studied vertebrates, where they include amygdala homologues located in the posterior half of the cerebral hemispheres, in close relationship with the chemosensory systems. Second, in all vertebrates, reward-seeking behaviours involve the activity of tegmento-striatal dopaminergic pathways, plus other inputs to the ventral striatum, including a…

Role of nitric oxide in pheromone-mediated intraspecific communication in mice

Nitric oxide is known to take part in the control of sexual and agonistic behaviours. This is usually attributed to its role in neural transmission in the hypothalamus and other structures of the limbic system. However, socio-sexual behaviours in rodents are mainly directed by chemical signals detected by the vomeronasal system, and nitric oxide is abundant in key structures along the vomeronasal pathway. Thus, here we check whether pharmacological treatments interfering with nitrergic transmission could affect socio-sexual behaviour by impairing the processing of chemical signals. Treatment with an inhibitor of nitric oxide synthesis (Nomega-Nitro-l-arginine methyl ester hydrochloride, L-N…

The GABAergic system of the dorsal cortex of lizards: a combined HRP-GABA immunohistochemistry study.

Abstract γ-Aminobutyric acid (GABA)-like immunoreactive (GABA-LI) neurons were found throughout the mediolateral and rostrocaudal axis of the dorsal cortex. They were horizontal, vertical and multipolar cells, mainly distributed in layers 1 and 3. GABA-LI boutons were diffusely distributed in layers 1 and 3, as well as forming basket-like images around layer 2 pyramidal perikarya. Double labelling experiments indicate that GABA-LI cells are an origin of and a target for rostrocaudal intrinsic projections within the dorsal cortex.

Amygdala

The amygdala is considered a key center in managing emotional information and its dysfunction is at the base of disorders ranging through anxiety, depression, PTSD and autism. However, the amygdala seems heterogeneous both structurally (with pallial and supallial components) and functionally. Thus, whereas cortical and thalamic multimodal sensory inputs enter the basolateral complex, the corticomedial amygdala is dominated by olfactory and vomeronasal inputs. Intrinsic amygdaloid circuitry, connects these two amygdaloid divisions and convey processed information to the main amygdala outputs. The pallial amygdala is the main source for telencephalic outputs to associative cortical areas (e.g…

Two interconnected functional systems in the amygdala of amniote vertebrates.

The amygdala shows ventropallial and lateropallial derivatives that can be compared among vertebrates according to their topological position, either superficial (cortical amygdala) or deep (basolateral amygdala and amygdalo-hippocampal area), connections and histochemical features. On the other hand, the subpallial amygdala, also called extended amygdala, is composed of medial and central divisions. In mammals, both divisions consist of an intra-amygdaloid portion and a part of the bed nucleus of the stria terminalis. In non-mammals, the intratelencephalic trajectory of the stria terminalis is short and both poles of the extended amygdala are close together. Like its mammalian counterpart,…

Septal complex of the telencephalon of lizards: III. Efferent connections and general discussion.

The projections of the septum of the lizard Podarcis hispanica (Lacertidae) were studied by combining retrograde and anterograde neuroanatomical tracing. The results confirm the classification of septal nuclei into three main divisions. The nuclei composing the central septal division (anterior, lateral, medial, dorsolateral, and ventrolateral nuclei) displayed differential projections to the basal telencephalon, preoptic and anterior hypothalamus, lateral hypothalamic area, dorsal hypothalamus, mammillary complex, dorsomedial anterior thalamus, ventral tegmental area, interpeduncular nucleus, raphe nucleus, torus semicircularis pars laminaris, reptilian A8 nucleus/ substantia nigra and cen…

The septal complex of the telencephalon of the lizardPodarcis hispanica. I. chemoarchitectonical organization

In this paper we study the septal complex architecture in the lizard Podarcis hispanica (Lacertidae). Histochemical and immunohistochemical techniques were used to define the distribution of zinc (Timm stain), acetyl cholinesterase (AChase), gamma-aminobutyric acid (GABA), tyrosine hydroxylase (TH), dopamine (DA), serotonin (5-HT), and two neuropeptides: leu-enkephalin (L-ENK) and substance P (SP). These reactions delineate a coherent map of nine septal nuclei that are named with a topographical nomenclature: anterior, lateral, ventromedial, medial, dorsolateral, ventrolateral, and dorsal septal nuclei, nucleus septalis impar, and nucleus of the posterior pallial commissure. The anterior se…