Vomeronasal Amygdala Research Articles

Integrating pheromonal and spatial information in the amygdalo-hippocampal network

Vomeronasal information is critical in mice for territorial behavior. Consequently, learning the territorial spatial structure should incorporate the vomeronasal signals indicating individual identity into the hippocampal cognitive map. In this work we show in mice that navigating a virtual environment induces synchronic activity, with causality in both directionalities, between the vomeronasal amygdala and the dorsal CA1 of the hippocampus in the theta frequency range. The detection of urine stimuli induces synaptic plasticity in the vomeronasal pathway and the dorsal hippocampus, even in animals with experimentally induced anosmia. In the dorsal hippocampus, this plasticity is associated with the overexpression of pAKT and pGSK3β. An amygdalo-entorhino-hippocampal circuit likely underlies this effect of pheromonal information on hippocampal learning. This circuit likely constitutes the neural substrate of territorial behavior in mice, and it allows the integration of social and spatial information.

GnRH neurogenesis depends on embryonic pheromone receptor expression

Gonadotropin-releasing hormone (GnRH) neurons control mammalian reproduction and migrate from their birthplace in the nasal placode to the hypothalamus during development. Despite much work on the origin and migration of GnRH neurons, the processes that control GnRH lineage formation are not fully understood. Here, we demonstrate that Nhlh genes control vomeronasal receptor expression in the developing murine olfactory placode associated with the generation of the first GnRH neurons at embryonic days (E)10–12. Inactivation of ß2-microglobulin (ß2-m), which selectively affects surface expression of V2Rs, dramatically decreased the number of GnRH neurons in the Nhlh2 mutant background, preventing rescue of fertility in female Nhlh2 mutant mice by male pheromones. In addition, we show that GnRH neurons generated after E12 fail to establish synaptic connections to the vomeronasal amygdala, suggesting the existence of functionally specialized subpopulations of GnRH neurons, which process pheromonal information.

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

Chemosensory 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 the nasal cavity and the vomeronasal pumping. In the amygdala, male stimuli are preferentially processed in the medial nucleus, whereas female cues induced a differential response in the posteromedial cortical amygdala. Thus, particular theta-gamma patterns in the olfactory network modulates the integration of chemosensory information in the amygdala, allowing the selection of an appropriate behaviour.

Contribution of pheromones processed by the main olfactory system to mate recognition in female mammals

Until recently it was widely believed that the ability of female mammals (with the likely exception of women) to identify and seek out a male breeding partner relied on the detection of non-volatile male pheromones by the female's vomeronasal organ (VNO) and their subsequent processing by a neural circuit that includes the accessory olfactory bulb (AOB), vomeronasal amygdala, and hypothalamus. Emperical data are reviewed in this paper that demonstrate the detection of volatile pheromones by the main olfactory epithelium (MOE) of female mice which, in turn, leads to the activation of a population of glomeruli and abutting mitral cells in the main olfactory bulb (MOB). Anatomical results along with functional neuroanatomical data demonstrate that some of these MOB mitral cells project to the vomeronasal amygdala. These particular MOB mitral cells were selectively activated (i.e., expressed Fos protein) by exposure to male as opposed to female urinary volatiles. A similar selectivity to opposite sex urinary volatiles was also seen in mitral cells of the AOB of female mice. Behavioral data from female mouse, ferret, and human are reviewed that implicate the main olfactory system, in some cases interacting with the accessory olfactory system, in mate recognition.

High convergence of olfactory and vomeronasal influence in the telencephalon of the terrestrial salamander Plethodon shermani

Previous work suggested that the telencephalic pathways of the main olfactory and vomeronasal systems of vertebrates are mostly isolated from each other, with the possible exception of convergence of the two systems into a small part of the olfactory amygdala. We tested the hypothesis of convergence between the main olfactory and vomeronasal systems by investigating the physiology of telencephalic olfactory responses in an in vitro brain preparation of the salamander Plethodon shermani. This animal was chosen because its olfactory and vomeronasal nerves can be separated and stimulated independently. The nerves were stimulated by short current pulses delivered through suction electrodes. Evoked field potentials and intracellular responses were systematically recorded in the telencephalon. The results showed an abundant overlap of olfactory and vomeronasal nerve-evoked field potentials in the ipsilateral lateral telencephalon and the amygdala. Single neurons receiving bimodal main olfactory and vomeronasal input were found in the dorsolateral telencephalon and amygdala. A classification of response latencies suggested that a subset of these neurons received direct input from both the main and accessory olfactory bulbs. Unimodal excitatory main olfactory responses were mostly found in neurons of the caudal telencephalic pole, but were also present in the striato-pallial transition area/lateral pallium region and striatum. Unimodal excitatory vomeronasal responses were found in neurons of the striato-pallial transition area, vomeronasal amygdala, and caudal amygdala. We conclude that the main olfactory and vomeronasal systems are extensively integrated within the salamander telencephalon and probably act in concert to modulate behavior.

A sex comparison of the anatomy and function of the main olfactory bulb–medial amygdala projection in mice

We previously reported that some main olfactory bulb (MOB) mitral/tufted (M/T) cells send a direct projection to the “vomeronasal” amygdala in female mice and selectively respond to volatile male mouse urinary odors. We asked whether MOB M/T cells that project to the vomeronasal amygdala exist in male mice and whether there is a sexually dimorphic response of these neurons to volatile male urinary pheromones. Gonadectomized male and female mice received bilateral injections of the retrograde tracer, Cholera toxin-B (CTb) into the medial amygdala (Me), which is part of the vomeronasal amygdala. All subjects were then treated with estradiol benzoate and progesterone before being exposed to volatile male urinary odors whereupon they were sacrificed 90 min later. Sections of the MOB were immunostained for Fos protein and/or CTb. Male mice, like females, displayed a small population of MOB M/T cells that project to the Me. While the general localization of these cells was similar in the two sexes, there were statistically significant sex differences in the percentage of MOB M/T cells in the anterior and posterior medial segments of the MOB that were retrogradely labeled by CTb. Male urinary volatiles stimulated equivalent, significant increases in Fos expression by MOB M/T neurons projecting to the Me in the two sexes. By contrast, in the same mice exposure to male urinary volatiles stimulated a significant increase in Fos expression by mitral cells in the accessory olfactory bulb (AOB) only in female subjects. Thus any sexually dimorphic behavioral or neuroendocrine responses to male urinary volatiles likely depend on the differential processing of these odor inputs in the AOB and/or other downstream forebrain structures after their detection by the main olfactory system.

Detection of conspecific pheromones elicits fos expression in GABA and calcium-binding cells of the rat vomeronasal system–medial extended amygdala

The olfactory accessory system is specialized in the detection of pheromones, being an afferent to medial extended amygdala. In spite of the fact that numerous phenotypes are found in these structures, in the current literature, there are no detailed descriptions about the phenotype of neurons in the vomeronasal system-medial extended amygdala after their activation by pheromonal stimuli. Using immunohistochemistry for fos and dual immunohistochemistry for fos and phenotypes, here we show that females have a greater number of activated neurons by the pheromonal stimulus. Likewise, a great colocalization of fos with GABA, calretinin, and calbindin was observed in the vomeronasal system-medial extended amygdala. These data suggest that in amygdaloid areas, neuronal excitability is controlled by GABAergic neurons that contain different calcium-binding proteins, indicating the important role of inhibitory control on the incoming sensory pheromonal and olfactory inputs controlled and processed by the vomeronasal system.

Trpc2 gene impacts on maternal aggression, accessory olfactory bulb anatomy and brain activity

The Trpc2 gene codes for an ion channel found in the vomeronasal organ (VNO). Studies using the Trpc2(-/-) (KO) mouse have exploited the gene's role in signal transduction to explore the VNO's role in pheromonally mediated behaviors. To date, no study has evaluated the impact of the Trpc2 gene on activity within the brain. In this study, we examine the gene's effect on brain regions governing maternal aggression. We intruder-tested lactating dams and then quantified Fos immunoreactivity (Fos-IR) in the vomeronasal amygdala, hypothalamus, olfactory regions and accessory olfactory bulb (AOB). Our data confirm previous reports that loss of the Trpc2 gene severely diminishes maternal aggression. We also show that deletion of the gene results in differential hypotrophy of the glomerular layer (GlA) of the AOB, with the anterior portion the GlA resembling that of wild-type mice, and the posterior portion reduced or absent. This anatomy is suggestive of residual functioning in the apical VNO of these animals. Our Fos study describes an impact of the deletion on a network of 21 brain regions involved in emotion, aggression and olfaction, suggesting that signals from the VNO mediate activity throughout the brain. Home-cage observations of KO dams show specific deficits in nest-building, suggesting a role for pup pheromones in inducing and maintaining pup-directed maternal behaviors as well as maternal aggression.

The organization of feedback projections in a pathway important for processing pheromonal signals

In most of the mammalian sensory systems there are massive cortical feedback projections to early processing stations. The mammalian accessory olfactory system is considered unique in several aspects. It is specialized for processing pheromonal signals and plays a critical role in regulating sociosexual behaviors. Furthermore, pheromonal signals are believed to bypass cortex and reach the hypothalamic behavioral centers after merely three forward projections. Because the organization of the feedback projections in the accessory olfactory system remains largely unclear, the importance of the feedback projections in the processing of pheromonal signals has been ignored. Here we show that in mice the feedback projections from the bed nucleus of stria terminalis (BST) and the vomeronasal amygdala to the accessory olfactory bulb (AOB) are topographically organized and use different neurotransmitters. By retrograde and anterograde tracing, we find that the feedback projection from the BST terminates in the AOB mitral cell layer, whereas that from the amygdala terminates in the AOB granule cell layer. By combining tracing, genetic labeling of GABAergic neurons, and immunostaining against a marker of glutamatergic synapses, we observe that the BST-to-AOB projection is GABAergic whereas the amygdala-to-AOB projection is glutamatergic. In addition, a substantial number of feedback neurons in the amygdala and BST express estrogen receptors. Thus, the accessory olfactory system, like other sensory systems, possesses extensive feedback projections. Moreover, our results suggest that central hormonal cues may modulate the processing of pheromonal signals at early stations through the precisely organized feedback projections.

Cytoarchitecture of the accessory olfactory bulb in the salamander Plethodon shermani

Plethodontid terrestrial salamanders are emerging models in the study of the evolution of chemical communication in vertebrates. Their vomeronasal system is well defined. It comprises sensory neurons in the epithelium of the vomeronasal organ, whose axons form the vomeronasal nerve projecting to the accessory olfactory bulb (AOB), which in turn projects to the vomeronasal amygdala through the accessory olfactory tract. A detailed description of the cellular elements of the urodele AOB is lacking. Neuronal morphology in the AOB was studied by means of biocytin intracellular injections and retrograde tract tracing in the salamander Plethodon shermani. The AOB exhibits the characteristic lamination of olfactory bulbs, except that it displays a mixed periglomerular and mitral somata layer superficially. Mitral cells are the only AOB neurons projecting to the vomeronasal amygdala. Each mitral cell sends multiple axonal branches, generally through both dorsal and ventral portions of the accessory olfactory tract. Some mitral cells additionally send axon collaterals in the white matter immediately ventral to the AOB. AOB interneurons are divided into superficial periglomerular and deep granule cells, each category exhibiting morphological variety. Some neurons in the granule cell layer of the AOB or the region ventral to the AOB have dendritic trees that cover both regions. The present study is the first to highlight the full anatomical extent of single AOB neurons and surprisingly suggests that the ventrolateral telencephalon found below the AOB is part of the salamander vomeronasal system.

Courtship pheromone–induced c-Fos-like immunolabeling in the female salamander brain

Plethodontid salamanders display intricate courtship behaviors. Proteinaceous courtship pheromones were recently discovered in the submandibular (mental) gland of the male Plethodon shermani, the red-legged salamander. Behavioral studies showed that these male pheromones are delivered by direct contact to the female snout and modulate her receptivity during courtship. Previous reports demonstrated that experimental application of courtship pheromones activates vomeronasal sensory neurons in P. shermani. The present study investigated the CNS response to courtship pheromones in that species using immunocytochemical detection of the immediate-early gene product c-Fos. The results show that application of a male gland extract to females activated Fos-like immunolabeling in the extended vomeronasal amygdala of the accessory olfactory system, as well as in the preoptic area and ventromedial hypothalamus; regions of the brain known to mediate reproductive responses in vertebrates. The gland extract additionally activated Fos-like labeling in the raphe median, possibly indicating a serotonergic activation. Application of individual purified courtship pheromone proteins resulted in increases in Fos-like labeling in some of the regions activated by the complete submandibular gland extract, but the pattern of labeling was not as clear as that of the complete extract. Unlike other known vertebrate reproductive pheromones, courtship pheromones in P. shermani were effective only at a high concentration. This could result from the particular mode of pheromone transfer in that species, which involves sustained direct contact between male and female. It is concluded that salamander courtship pheromones exert their influence on behavior through the vomeronasal pathway and its direct projections to the preoptic and hypothalamic regions.

Development of the vomeronasal amygdala in anuran amphibians: Hodological, neurochemical, and gene expression characterization

The organization of the amygdaloid complex in amphibians possesses major features shared with amniotes. Basic subdivisions have been identified and tentatively compared with their counterparts in other tetrapods. However, problems appeared when trying to find homologies for the amphibian vomeronasal amygdala, the medial amygdala (MeA), because of its embryological origin and, therefore, its evolutionary significance could not be established. Thus, in the present study the main characteristics of the MeA in anurans were studied during development by means of tract-tracing, immunohistochemical, and gene expression techniques. The connectivity of the MeA, mainly related to the accessory olfactory bulb and the hypothalamus, and the localization of neurochemical markers such as substance P, somatostatin, and GABA strongly support its homology with the medial amygdala (subpallial) of mammals. In addition, analysis of the expression patterns of the LIM-homeodomain genes x-Lhx5/7/9 in the developing MeA, together with the immunohistochemistry for GABA and the transcription factor NKX2.1, evidence its resemblance to the subpallial component of the vomeronasal amygdala of mammals in terms of embryological origin and, most likely, the presence of migrated cells from other territories. No evidence was found for pallial-derived territories in the vomeronasal amygdala of anurans that could be comparable to the cortical portions that exist in amniotes, suggesting that these cortical components have emerged in the anamnio-amniotic transition in the evolution of tetrapods.

Segregated pathways to the vomeronasal amygdala: differential projections from the anterior and posterior divisions of the accessory olfactory bulb

Apically and basally located receptor neurons in the vomeronasal sensory epithelium express G(i2 alpha)- and G(o alpha)-proteins, V1R and V2R vomeronasal receptors, project to the anterior and posterior accessory olfactory bulb and respond to different stimuli, respectively. The extent to which secondary projections from the two portions of the accessory olfactory bulb are convergent in the vomeronasal amygdala is controversial. This issue is addressed by using anterograde and retrograde tract-tracing methods in rats including electron microscopy. Injections of dextran-amines, Fluoro Gold, cholera toxin-B subunit and Fast Blue were delivered to the anterior and posterior accessory olfactory bulb, bed nucleus of the stria terminalis, dorsal anterior amygdala and bed nucleus of the accessory olfactory tract/anteroventral medial amygdaloid nucleus. We have demonstrated that, apart from common vomeronasal-recipient areas, only the anterior accessory olfactory bulb projects to the bed nucleus of the stria terminalis, medial division, posteromedial part, and only the posterior accessory olfactory bulb projects to the dorsal anterior amygdala and deep cell layers of the bed nucleus of the accessory olfactory tract and the anteroventral medial amygdaloid nucleus. These results provide evidence that, excluding areas of convergence, the V1R and V2R vomeronasal pathways project to specific areas of the amygdala. These two vomeronasal subsystems are therefore anatomically and functionally separated in the telencephalon.

Organization of the pallium in the fire‐bellied toad Bombina orientalis. I: Morphology and axonal projection pattern of neurons revealed by intracellular biocytin labeling

The cytoarchitecture and axonal projection pattern of pallial areas was studied in the fire-bellied toad Bombina orientalis by intracellular injection of biocytin into a total of 326 neurons forming 204 clusters. Five pallial regions were identified, differing in morphology and projection pattern of neurons. The rostral pallium receiving the bulk of dorsal thalamic afferents has reciprocal connections with all other pallial areas and projects to the septum, nucleus accumbens, and anterior dorsal striatum. The medial pallium projects bilaterally to the medial pallium, septum, nucleus accumbens, mediocentral amygdala, and hypothalamus and ipsilaterally to the rostral, dorsal, and lateral pallium. The ventral part of the medial pallium is distinguished by efferents to the eminentia thalami and the absence of contralateral projections. The dorsal pallium has only ipsilateral projections running to the rostral, medial, and lateral pallium; septum; nucleus accumbens; and eminentia thalami. The lateral pallium has ipsilateral projections to the olfactory bulbs and to the rostral, medial, dorsal, and ventral pallium. The ventral pallium including the striatopallial transition area (SPTA) has ipsilateral projections to the olfactory bulbs, rostral and lateral pallium, dorsal striatopallidum, vomeronasal amygdala, and hypothalamus. The medial pallium can be tentatively homologized with the mammalian hippocampal formation, the dorsal pallium with allocortical areas, the lateral pallium rostrally with the piriform and caudally with the entorhinal cortex, the ventral pallium with the accessory olfactory amygdala. The rostral pallium, with its projections to the dorsal and ventral striatopallidum, resembles the mammalian frontal cortex.

Species‐specific chemosignals evoke delayed excitation of the vomeronasal amygdala in freely‐moving female rats

Male rat chemosignals attract females and influence their reproductive status. Through the accessory olfactory bulb and its projection target, the posteromedial cortical nucleus of the amygdala (PMCo), species-specific chemosignals detected by the vomeronasal organ (VNO) may reach the hypothalamus. To test this hypothesis in vivo, behavioural activation and neurotransmitter release in the PMCo were simultaneously monitored in freely moving female oestrus rats exposed to either rat or mouse urinary stimuli, or to odorants. Plasma levels of the luteinizing hormone were subsequently monitored. All stimuli induced an immediate behavioural activation, but only species-specific chemosignals led to a delayed behavioural activation. This biphasic behavioural activation was accompanied by a VNO-mediated release of the excitatory amino acids, aspartate and glutamate, in the PMCo. The late behavioural and neurochemical activation was followed by an increase in the levels of circulating luteinizing hormone. In conclusion, these data show that only species-specific chemosignals induce a delayed behavioural activation and excitatory activation of the PMCo, which is dependent on an intact VNO.

General organization of the perinatal and adult accessory olfactory bulb in mice

The vomeronasal system is currently a topical issue since the dual functional specificity, vomeronasal system-pheromones, has recently been questioned. Irrespective of the tools used to put such specificity in doubt, the diversity of the anatomy of the system itself in the animal kingdom is probably of more importance than has previously been considered. It has to be pointed out that a true vomeronasal system is integrated by the vomeronasal organ, the accessory olfactory bulb, and the so-called vomeronasal amygdala. Therefore, it seems reasonable to establish the corresponding differences between a well-developed vomeronasal system and other areas of the nasal cavity in which putative olfactory receptors, perhaps present in other kinds of mammals, may be able to detect pheromones and to process them. In consequence, a solid pattern for one such system in one particular species needs to be chosen. Here we report on an analysis of the general morphological characteristics of the accessory olfactory bulb in mice, a species commonly used in the study of the vomeronasal system, during growth and in adults. Our results indicate that the critical period for the formation of this structure comprises the stages between the first and the fifth day after birth, when the stratification of the bulb, the peculiarities of each type of cell, and the final building of glomeruli are completed. In addition, our data suggest that the conventional plexiform layers of the main olfactory bulb are not present in the accessory bulb.

Sex difference in Fos induced by male urine in medial amygdala-projecting accessory olfactory bulb mitral cells of mice

We previously reported that exposure to soiled male bedding induced Fos protein immunoreactivity (Fos-IR) in significantly more neurons of the vomeronasal organ (VNO) and medial amygdala of gonadectomized, estradiol-treated female than male mice whereas no such sex difference was seen in the intervening mitral cells of the accessory olfactory bulb (AOB). We asked whether a sexually dimorphic functional response to male urinary pheromones might be revealed in AOB mitral cells that project specifically to the medial amygdala. Gonadectomized mice of both sexes were treated with estradiol and 3 days later received bilateral injections of the retrograde tracer, Cholera toxin-B (CTB) into the medial amygdala. Five days later male urine or saline was applied nasally to each subject 90 min prior to sacrifice, and sections of the AOB were processed for double-label fluorescent immunocytochemistry for Fos protein and CTB. In both the rostral and caudal AOB, there were significantly more double-labeled mitral cells in female than in male subjects following exposure to male urine. A sex difference in the responsiveness of VNO sensory neurons seen previously to male soiled bedding is reflected in a parallel sex difference in the responsiveness of AOB mitral cells when only AOB cells that project to the amygdala are examined and when male urine as opposed to soiled male bedding is used as the activating stimulus.

Efferent connections of the main olfactory bulb in the opossum ( Monodelphis domestica): A characterization of the olfactory entorhinal cortex in a marsupial

Olfactory projections have been investigated for decades, but few reports using modern, sensitive neural tracers are available. In marsupials, only lesion-degeneration studies exist and they are restricted to the genera Didelphis and Trichosurus. Some of the territories described as olfactory-recipient such as the upper portion of the rhinal fissure and the vomeronasal amygdala are, however, controversial. Also, the characterization of the olfactory portion of the entorhinal cortex is far from clear in acallosal mammals. The present report investigates, using biotinylated dextran-amine, the olfactory connections in the short-tailed opossum ( Monodelphis domestica) and characterizes the olfactory portion of the entorhinal cortex in non-placental mammals. The data indicate that olfactory projections do not reach the upper portion of the rhinal fissure, but partially end in the vomeronasal amygdala, i.e., the medial and posteromedial cortical amygdaloid nuclei; thus, although olfactory and vomeronasal system have largely segregated outputs, areas of overlap should be restudied. The olfactory portion of the entorhinal cortex is much larger than previously described, extending up to the occipital pole of the cerebral hemisphere. Collectively, these data contribute to our understanding of the organization of the hippocampal formation in marsupials.

Feedback Loops Link Odor and Pheromone Signaling with Reproduction

Pheromones can have profound effects on reproductive physiology and behavior in mammals. To investigate the neural circuits underlying these effects, we used a genetic transneuronal tracer to identify neurons that synapse with GnRH (LHRH) neurons, the key regulators of reproduction. We then asked whether the connected neurons are presynaptic or postsynaptic to GnRH neurons and analyzed their responses to chemosensory cues. Surprisingly, these experiments indicate that GnRH neurons receive pheromone signals from both odor and pheromone relays in the brain and may also receive common odor signals. Moreover, feedback loops are evident whereby GnRH neurons could influence both odor and pheromone processing. Remarkably, approximately 800 GnRH neurons communicate with approximately 50,000 neurons in 53 functionally diverse brain areas, with some connections exhibiting sexual dimorphism. These studies reveal a complex interplay between reproduction and other functions in which GnRH neurons appear to integrate information from multiple sources and modulate a variety of brain functions.

Connectivity and cytoarchitecture of telencephalic centers in the fire-bellied toad Bombina orientalis

In the fire-bellied toad Bombina orientalis, the connectivity and cytoarchitecture of telencephalic structures were studied by intracellular, anterograde and retrograde biocytin labelling in order to elucidate the neuronal basis of fear conditioning and context learning in amphibians. Our findings suggest the existence of a central amygdala-bed nucleus of the stria terminalis complex in the caudal mid-ventral telencephalon, a vomeronasal amygdala in the caudolateral ventral telencephalon, an olfactory amygdala in the caudal pole of the telencephalon lateral of the vomeronasal amygdala, and a ventromedially situated “medial” amygdala, which is assumed to be functionally equivalent to the basolateral amygdala of mammals. A ventromedial cellular column forms a nucleus accumbens rostrally and continues caudally into a shell-like ventral pallidum. A lateral column constitutes a dorsal striatum proper rostrally, a dorsal pallidum caudally, and a mixed striato-pallidum at intermediate levels. We conclude that the caudal mediolateral complex consisting of an extended central, vomeronasal and olfactory amygdala of anurans represents the ancestral equivalent of the amygdaloid complex of tetrapods. During the evolution of the mammalian telencephalon, this complex apparently was shifted medially and involuted.