Anterior Cortical Nucleus Research Articles

Changes in the Ultrastructure of Synapses in the Anterior Cortical Nucleus of the Amygdaloid Body of the Brain in Female Rats in Relation to Sex Hormone Levels

We present here an analysis of the ultrastructural characteristics of synapses in the anterior cortical nucleus of the amygdaloid body of the brain in female WAG/Rij rats (n = 9) with different levels of female sex hormones. The results of this study demonstrated that ovariectomy led to structural changes in synapses and decreases in the total number of synapses as compared with the control group, while hormone replacement therapy led to recovery of synapse structure and number. In terms of the level of dense projections, the control and post-ovariectomy groups were dominated by asymmetrical synapses (52%); in terms of the type of curvature of the plane of the synaptic contact, synapses with positively curved contacts dominated. Replacement therapy was followed by a minor decrease in the number of asymmetrical synapses (47%), most having negatively curved contacts. Complex synaptic contacts of the divergent and convergent types were seen, which is evidence that contacts were in an active functional state. The number of perforated synapses increased significantly from 14.3 to 50%, which may be evidence of estrogen activation of synapses.

Reactive changes in morphological and morphometric parameters of immunopositive astrocytes of the amygdala in response to hormone level in absence epilepsy

To study the changes in the morphological and morphometric parameters of immunopositive astrocytes of the amygdala in absence epilepsy depending on hormonal profile. Adult female WAG/Rij rats were used as experimental subjects. The astrocytes were detected on serial sections using a reaction to glial fibrillary acidic protein (GFAP) with pre-stained hematoxylin. Quantitative analysis was carried out for a 204.8´153.6 μm2 field of view. In the control group, astrocytes had a relatively regular stellate form and GFAP was moderately expressed in their bodies and processes. The number of astrocytes was 18.20±2.87, and their area was 164±3.29 μm2. After ovariectomy, a high expression of the protein, both in the bodies and in the processes of astrocytes, increasing the cell size to 188.85±4.97 μm2 (p<0.05) was observed. The astrocytes increased to 34.55±3.03 (p<0.05). In addition, the deformation of the processes and their diffuse defibration were observed. After hormone replacement therapy, a decrease in GFAP expression was detected, the area of astrocytes became smaller in comparison with the group after ovariectomy: 173.54±5.48 μm2 (p<0.05). Morphological changes in glial cells were manifested as a decrease in the size of their bodies, the processes became smooth without diffuse sprouting and swelling, which is probably associated with neuroprotective functions of estradiol. Thus, the results of our study demonstrated that the deficiency of female sex hormones led to the increase in both the amount and area of astrocytes in the anterior cortical nucleus of the amygdala, and hormone replacement therapy positively affected the structural and quantitative characteristics of astrocytes due to the endogenous protective role of estradiol.

Nuclear organization of the African elephant (Loxodonta africana) amygdaloid complex: an unusual mammalian amygdala.

Here we describe the nuclear organization of the African elephant amygdaloid complex using Nissl, myelin, and a range of immunohistochemical stains. The African elephant is thought to exhibit many affect-laden and social-empathic behaviours; however, to date the amygdaloid complex, which is the generator of emotional states of the brain is yet to be fully explored in the elephants. For the most part, the amygdaloid complex of the African elephant is similar to that observed in other mammals in terms of the presence of nuclei and their topological relationships; however, we did observe several specific differences in amygdaloid organization. The elephant amygdala has undergone rotation in both the coronal and sagittal planes, seemingly associated with the expansion of the temporal lobe. Numerous scalloped cell clusters, termed glomeruli, forming the intermediate nuclei of the basal, accessory basal and central nuclear groups, were occupied by structures immunopositive to doublecortin. The nuclei typically associated with the accessory olfactory system (posterior cortical nucleus and medial nuclear complex) were absent from the elephant amygdala. The anterior cortical nucleus is very large and appears to be comprised of two subdivisions. The lateral nuclear complex is expanded and has two novel subdivisions. The amygdalohippocampal area appears relatively enlarged. The numerous shared and derived characters make the elephant amygdaloid complex very unusual and unique amongst mammals, but the derived characters appear to relate to observed elephant affect-laden behaviours.

Association of monoamine oxidase-A genetic variants and amygdala morphology in violent offenders with antisocial personality disorder and high psychopathic traits

Violent offending is elevated among individuals with antisocial personality disorder (ASPD) and high psychopathic traits (PP). Morphological abnormalities of the amygdala and orbitofrontal cortex (OFC) are present in violent offenders, which may relate to the violence enacted by ASPD + PP. Among healthy males, monoamine oxidase-A (MAO-A) genetic variants linked to low in vitro transcription (MAOA-L) are associated with structural abnormalities of the amygdala and OFC. However, it is currently unknown whether amygdala and OFC morphology in ASPD relate to MAO-A genetic polymorphisms. We studied 18 ASPD males with a history of violent offending and 20 healthy male controls. Genomic DNA was extracted from peripheral leukocytes to determine MAO-A genetic polymorphisms. Subjects underwent a T1-weighted MRI anatomical brain scan that provided vertex-wise measures of amygdala shape and surface area and OFC cortical thickness. We found that ASPD + PP subjects with MAOA-L exhibited decreased surface area in the right basolateral amygdala nucleus and increased surface area in the right anterior cortical amygdaloid nucleus versus healthy MAOA-L carriers. This study is the first to describe genotype-related morphological differences of the amygdala in a population marked by high aggression. Deficits in emotional regulation that contribute to the violence of ASPD + PP may relate to morphological changes of the amygdala under genetic control.

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 posterior intralaminar thalamus, and moderate projections from the posterior bed nucleus of the stria terminalis, mesocortical structures and the hippocampal formation. Remarkably, the ACo projects moderately to the central nuclei of the amygdala and anterior bed nucleus of the stria terminalis, and densely to the lateral hypothalamus. Finally, minor connections are present with some midbrain and brainstem structures. The afferent projections of the ACo indicate that this nucleus might play a role in emotional learning involving chemosensory stimuli, such as olfactory fear conditioning. The efferent projections confirm this view and, given its direct output to the medial part of the central amygdala and the hypothalamic 'aggression area', suggest that the ACo can initiate defensive and aggressive responses elicited by olfactory or, to a lesser extent, vomeronasal stimuli.

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 the CxA receives a relatively restricted set of intratelencephalic connections, originated mainly by the olfactory system and basal forebrain, with minor afferents from the amygdala. The only relevant extratelencephalic afference originates in the ventral tegmental area (VTA). The efferent projections of the CxA reciprocate the inputs from the piriform cortex and olfactory amygdala. In addition, the CxA projects densely to the basolateral amygdaloid nucleus and the olfactory tubercle. The extratelencephalic projections of the CxA are very scarce, and target mainly hypothalamic structures. The pattern of connections of the CxA suggests that it is indeed a transitional area between the piriform cortex and the cortical amygdala. Double labeling with choline acetyltransferase indicates that the afferent projection from the basal forebrain is the origin of its distinctive cholinergic innervation, and double labeling with dopamine transporter shows that the projection from the VTA is the source of dopaminergic innervation. These connectivity and neurochemical features, together with the fact that it receives vomeronasal in addition to olfactory information, suggest that the CxA may be involved in processing olfactory information endowed with relevant biological meaning, such as odors related to reproductive or defensive behaviors.

Connections of the magnocellular medial preoptic nucleus (MPN mag) in male Syrian hamsters. II. The efferents

The magnocellular medial preoptic nucleus (MPN mag) plays a critical role in the regulation of male copulatory behavior in the Syrian hamster. Our study of the afferents are consistent with the hypothesis that the MPN mag receives input from areas in the chemosensory pathway and nuclear groups that contain receptors for gonadal steroids (Wang and Swann, 2006). The goal of the present study is to identify targets of the MPN mag by describing the location of labeled fibers following an injection of biotinylated dextran amine (BDA) into the MPN mag. Our results indicate that targets of the MPN mag include: (1) brainstem nuclei implicated in regulating male mating behavior in other species, such as the periaqueductal gray, deep mesencephalic nucleus, retrorubral field, ventral tegmental area and lateral paragigantocellular nucleus and (2) steroid-concentrating nuclei in the septum, preoptic area and hypothalamus. The lack of projections from the MPN mag to its chemosensory afferents indicate that the connections of the MPN mag with the posterior medial bed nucleus of the stria terminalis, medial and anterior cortical nuclei of the amygdala are unidirectional, and that chemosensory information flows from the medial amygdala and bed nucleus of the stria terminalis (BST) to the MPN mag. The bidirectional nature of the connections between the MPN mag and steroid-concentrating nuclei suggest that the MPN mag may influence the function of a steroid-concentrating network that regulates behaviors. Together these results support the hypothesis that the MPN mag regulates male mating behavior by integrating chemosensory and hormonal signals and relaying this information to brainstem areas that control motor output.

Electrical Resonance in the θ Frequency Range in Olfactory Amygdala Neurons

The cortical amygdala receives direct olfactory inputs and is thought to participate in processing and learning of biologically relevant olfactory cues. As for other brain structures implicated in learning, the principal neurons of the anterior cortical nucleus (ACo) exhibit intrinsic subthreshold membrane potential oscillations in the θ-frequency range. Here we show that nearly 50% of ACo layer II neurons also display electrical resonance, consisting of selective responsiveness to stimuli of a preferential frequency (2–6 Hz). Their impedance profile resembles an electrical band-pass filter with a peak at the preferred frequency, in contrast to the low-pass filter properties of other neurons. Most ACo resonant neurons displayed frequency preference along the whole subthreshold voltage range. We used pharmacological tools to identify the voltage-dependent conductances implicated in resonance. A hyperpolarization-activated cationic current depending on HCN channels underlies resonance at resting and hyperpolarized potentials; notably, this current also participates in resonance at depolarized subthreshold voltages. KV7/KCNQ K+ channels also contribute to resonant behavior at depolarized potentials, but not in all resonant cells. Moreover, resonance was strongly attenuated after blockade of voltage-dependent persistent Na+ channels, suggesting an amplifying role. Remarkably, resonant neurons presented a higher firing probability for stimuli of the preferred frequency. To fully understand the mechanisms underlying resonance in these neurons, we developed a comprehensive conductance-based model including the aforementioned and leak conductances, as well as Hodgkin and Huxley-type channels. The model reproduces the resonant impedance profile and our pharmacological results, allowing a quantitative evaluation of the contribution of each conductance to resonance. It also replicates selective spiking at the resonant frequency and allows a prediction of the temperature-dependent shift in resonance frequency. Our results provide a complete characterization of the resonant behavior of olfactory amygdala neurons and shed light on a putative mechanism for network activity coordination in the intact brain.

Neuropeptide S Facilitates Mice Olfactory Function through Activation of Cognate Receptor-Expressing Neurons in the Olfactory Cortex

Neuropeptide S (NPS) is a newly identified neuromodulator located in the brainstem and regulates various biological functions by selectively activating the NPS receptors (NPSR). High level expression of NPSR mRNA in the olfactory cortex suggests that NPS-NPSR system might be involved in the regulation of olfactory function. The present study was undertaken to investigate the effects of intracerebroventricular (i.c.v.) injection of NPS or co-injection of NPSR antagonist on the olfactory behaviors, food intake, and c-Fos expression in olfactory cortex in mice. In addition, dual-immunofluorescence was employed to identify NPS-induced Fos immunereactive (-ir) neurons that also bear NPSR. NPS (0.1–1 nmol) i.c.v. injection significantly reduced the latency to find the buried food, and increased olfactory differentiation of different odors and the total sniffing time spent in olfactory habituation/dishabituation tasks. NPS facilitated olfactory ability most at the dose of 0.5 nmol, which could be blocked by co-injection of 40 nmol NPSR antagonist [D-Val5]NPS. NPS administration dose-dependently inhibited food intake in fasted mice. Ex-vivo c-Fos and NPSR immunohistochemistry in the olfactory cortex revealed that, as compared with vehicle-treated mice, NPS markedly enhanced c-Fos expression in the anterior olfactory nucleus (AON), piriform cortex (Pir), ventral tenia tecta (VTT), the anterior cortical amygdaloid nucleus (ACo) and lateral entorhinal cortex (LEnt). The percentage of Fos-ir neurons that also express NPSR were 88.5% and 98.1% in the AON and Pir, respectively. The present findings demonstrated that NPS, via selective activation of the neurons bearing NPSR in the olfactory cortex, facilitates olfactory function in mice.

Зміни експресії гена c-fos в ядрах мигдалеподібного тіла та частоти серцевих скорочень при реалізації їжодобувних стереотипних рухів у щурів

The distribution of Fos-immunoreactive (Fos-ir) and NADPH Diaphorase reactive (NADPH-dr-) neurons in the different subnuclei of amygdala and insular cortex (on the level -2,12 to -3,14 mm from bregma), and the associated changes of heart rate (HR) in intact, food-deprivated and executed food-procuring movements of rats were studied. In comparison with other groups of animals, the mean number of the Fos-ir neurons in the central nucleus of amygdala (Ce) and the insular cortex (GI/DI) at all studied levels was significantly greater in the executed food-procuring movements in rats. The main focus of localization of the Fos-ir neurons was found in lateral part of the Ce (58.5 +/- 1.9 units in 40-microm-thick section) at the level -2.56 mm. The mean number of Fos-ir neurons was significantly greater also in the lateral and capsular parts of the Ce. The mean number of Fos-ir neurons in the GI/DI was 165.5 +/- 3.2 cells in section. The number and density of NADPH-d reactive neurons was not significantly different in the brain structures of all animal groups studied. The double stained neurons (Fos-ir + NADPH-dr) were registered in medial, basolateral, anterior cortical amygdaloid nuclei and substantia innominata (SI) in rats after realization food-procuring movements. It was found that realization of food-procuring movements by the forelimb during repeated sessions was accompanied with the gradual decline of mean values of the HR (from 5% to 12% of control level) with subsequent renewal of them to the initial values (tonic component). The analysis of dynamics of the HR changes during realization of separate purposeful motion has shown the transient period of the HR suppression (500 ms), which coincided with the terminal phase of grasping of food pellet (phasic component). We suggest that the revealed focuses of localization of Fos-ir neurons in the lateral and medial subregions of amigdaloid Ce and also GI/DI, and SI testified that these structures of brain are involved in generation of the goal-directed motions. Direct projections of these subnuclei (and hypothalamus) to the cardiovascular centers of the medulla determine the associated regulation of the cardiovascular system function in the period of realization of the goal-directed motions in animals.

Projections from the anterior basomedial and anterior cortical amygdaloid nuclei to melanin-concentrating hormone-containing neurons in the lateral hypothalamus of the rat

Melanin-concentrating hormone (MCH) is involved in the regulation of feeding behavior as well as in goal oriented behaviors, and MCH-containing neurons are distributed mainly in the lateral hypothalamic area (LHA). The anterior basomedial nucleus (BMA) and anterior cortical nucleus (CoA) of the amygdala form part of a circuit involved in processing olfactory, gustatory and visceral information, and the BMA-LHA and CoA-LHA pathways are suggested to be implicated in the control of feeding behavior. However, it is still unknown whether or not MCH-containing LHA neurons are under the direct influence of the BMA and CoA. Here the organization of projections from the BMA and CoA to MCH-containing LHA neurons was examined. Using a combined anterograde tracing with biotinylated dextranamine and immunohistochemistry for MCH, we first demonstrated that the distribution pattern of BMA fibers was almost similar to that of CoA fibers in the LHA, and a prominent overlapping distribution of these fibers and MCH-immunoreactive neurons existed in the ventral peripeduncular region of the LHA. We further revealed that asymmetrical synapses were made between these fibers and neurons. Using a combination of retrograde tract-tracing with cholera toxin B subunit and in situ hybridization for vesicular glutamate transporter (VGLUT) 2 mRNA, we finally showed that most of the LHA-projecting BMA and CoA neurons expressed VGLUT2 mRNA. These data suggest that the BMA and CoA of the amygdala may exert excitatory influence upon the MCH-containing LHA neurons for the regulation of feeding behavior.

Female Mice Deficient in Alpha-Fetoprotein Show Female-Typical Neural Responses to Conspecific-Derived Pheromones

The neural mechanisms controlling sexual behavior are sexually differentiated by the perinatal actions of sex steroid hormones. We recently observed using female mice deficient in alpha-fetoprotein (AFP-KO) and which lack the protective actions of AFP against maternal estradiol, that exposure to prenatal estradiol completely defeminized the potential to show lordosis behavior in adulthood. Furthermore, AFP-KO females failed to show any male-directed mate preferences following treatment with estradiol and progesterone, indicating a reduced sexual motivation to seek out the male. In the present study, we asked whether neural responses to male- and female-derived odors are also affected in AFP-KO female mice. Therefore, we compared patterns of Fos, the protein product of the immediate early gene, c-fos, commonly used as a marker of neuronal activation, between wild-type (WT) and AFP-KO female mice following exposure to male or estrous female urine. We also tested WT males to confirm the previously observed sex differences in neural responses to male urinary odors. Interestingly, AFP-KO females showed normal, female-like Fos responses, i.e. exposure to urinary odors from male but not estrous female mice induced equivalent levels of Fos protein in the accessory olfactory pathways (e.g. the medial part of the preoptic nucleus, the bed nucleus of the stria terminalis, the amygdala, and the lateral part of the ventromedial hypothalamic nucleus) as well as in the main olfactory pathways (e.g. the piriform cortex and the anterior cortical amygdaloid nucleus), as WT females. By contrast, WT males did not show any significant induction of Fos protein in these brain areas upon exposure to either male or estrous female urinary odors. These results thus suggest that prenatal estradiol is not involved in the sexual differentiation of neural Fos responses to male-derived odors.

Projections of the central medial nucleus of the thalamus in the rat: Node in cortical, striatal and limbic forebrain circuitry

The central medial nucleus (CM) of thalamus is a prominent cell group of the rostral intralaminar complex of the thalamus. No previous report in the rat has comprehensively described the projections of CM. Using the anterograde anatomical tracer, Phaseolus vulgaris leucoagglutinin, we examined the efferent projections of CM, comparing projections from rostral (CMr) and caudal (CMc) regions of CM. We showed that the central medial nucleus distributes substantially to several cortical sites and to a limited number of subcortical structures. The primary CM targets were anterior and posterior regions of cortex, the claustrum, the caudate-putamen, the nucleus accumbens (ACC), the olfactory tubercle, and the amygdala. CMr and CMc distribute to several of the same structures but essentially to different parts of these structures. By comparison, CMr more strongly targets limbic structures, CMc more heavily sensorimotor structures. Main CMr projection sites were the medial agranular, anterior cingulate, prelimbic, dorsolateral orbital and dorsal agranular insular cortices, the dorsal striatum, the ACC, and the basolateral nucleus of the amygdala. Main CMc cortical projection sites were the ventrolateral, lateral and dorsolateral orbital cortices, dorsal, ventral and posterior agranular insular cortices, visceral cortex, primary somatosensory and motor cortices, and perirhinal cortex. Main CMc subcortical projection sites were the dorsal striatum and the lateral, central, anterior cortical, and basomedial nuclei of amygdala. The largely complementary output of CMr and CMc to diverse areas of cortex and to regions of the striatum and amygdala suggest a combined CM influence over a widespread area of the anterior cortex and throughout the dorsal and ventral striatum and the amygdala. CM projections to limbic and sensorimotor structures of the rostral forebrain suggest that CM may serve to integrate affective, cognitive and sensorimotor functions for goal-directed behavior.

The intrinsic connectome of the rat amygdala.

The connectomes of nervous systems or parts there of are becoming important subjects of study as the amount of connectivity data increases. Because most tract-tracing studies are performed on the rat, we conducted a comprehensive analysis of the amygdala connectome of this species resulting in a meta-study. The data were imported into the neuroVIISAS system, where regions of the connectome are organized in a controlled ontology and network analysis can be performed. A weighted digraph represents the bilateral intrinsic (connections of regions of the amygdala) and extrinsic (connections of regions of the amygdala to non-amygdaloid regions) connectome of the amygdala. Its structure as well as its local and global network parameters depend on the arrangement of neuronal entities in the ontology. The intrinsic amygdala connectome is a small-world and scale-free network. The anterior cortical nucleus (72 in- and out-going edges), the posterior nucleus (45), and the anterior basomedial nucleus (44) are the nuclear regions that posses most in- and outdegrees. The posterior nucleus turns out to be the most important nucleus of the intrinsic amygdala network since its Shapley rate is minimal. Within the intrinsic amygdala, regions were determined that are essential for network integrity. These regions are important for behavioral (processing of emotions and motivation) and functional (memory) performances of the amygdala as reported in other studies.

Expression of Oestrogen Receptor α in the Brain of Brandt’s Voles (Lasiopodomys brandtii ): Sex Differences and Variations During Ovarian Cycles

Oestrogen receptor (ER) α plays an important role in a variety of cognitive and behavioural functions. It has been shown that ERα expression in the brain is sexually dimorphic and is influenced by circulating oestrogen. In the present study, we mapped ERα-immunoreactive (-ir) cells in the forebrain of Brandt's voles (Lasiopodomys brandtii) to examine differences in ERα-ir expression between males and females and to reveal variations of ERα-ir expression during ovarian cycles in females. ERα-ir cells were found in many forebrain regions, including the lateral septum, bed nucleus of the stria terminalis, medial preoptic area (MPOA), anterior, arcuate and ventral medial (VMH) nuclei of the hypothalamus, as well as medial (MeA) and anterior cortical nuclei of the amygdala. Females had more ERα-ir cells in the VMH than males. Females during ovarian oestrus, but not di-oestrus or pro-oestrus, also had more ERα-ir cells in the MPOA than males. Furthermore, females in ovarian di-oestrus or oestrus had more ERα-ir cells in the MeA than males. Together, these data indicate that ERα expression in the brain of Brandt's voles is sexually dimorphic in specific brain areas. In addition, variations in the levels of circulating oestrogen during ovarian cycles can affect ERα expression in the female brain in a region-specific manner.

Orexinergic innervation of the extended amygdala and basal ganglia in the rat

The orexinergic system interacts with several functional states of emotions, stress, hunger, wakefulness and behavioral arousal through four pathways originating in the lateral hypothalamus (LH). Hundreds of orexinergic efferents have been described by tracing studies and direct immunohistochemistry of orexin in the forebrain, olfactory regions, hippocampus, amygdala, septum, basal ganglia, thalamus, hypothalamus, brain stem and spinal cord. Most of these tracing studies investigated the whole orexinergic projection to all regions of the intracranial part of the CNS. To identify the orexinergic efferents at the subnuclear level of resolution, we focussed on the orexinergic target in the amygdala, which is substantially involved in the LH output and contributes mostly to the functional outcome of the orexinergic system and the basal ganglia. Immunohistochemical identification of axonal orexin A and orexin B in male adult rats has been performed on serial sections. In the extended amygdala many new orexinergic targets were found in the anterior amygdaloid area (dense), anterior cortical nucleus (moderate), amygdalostriatal transition region (moderate), basolateral regions (moderate), basomedial nucleus (moderate), several bed nucleus of the stria terminals regions (few to dense), central amygdaloid subdivisions (dense), posteromedial cortical nucleus (moderate) and medial amygdaloid subnuclei (dense). Furthermore, the entopeduncular nucleus has been newly identified as another target for orexinergic fibers with a high density. These results suggest that subdivisions and subnuclei of the extended amygdala are specific targets of the orexinergic system.

Agonistic encounters and brain activation in dominant and subordinate male greater long-tailed hamsters

During an agonistic encounter test, dominant male greater long-tailed hamsters ( Tscheskia triton) initiated attacks sooner and displayed higher levels of aggression and flank marking behavior than their subordinate counterparts. Accordingly, subordinate males exhibited more defensive behavior than dominant ones. Specific patterns of neuronal activation, measured by Fos-immunoreactive staining (Fos-ir), were found in the hamster brain following agonistic interactions. Increased Fos-ir was observed in the bed nucleus of the stria terminalis (BST), ventromedial hypothalamus (VMH), and medial (MeA) and anterior cortical (ACo) nuclei of the amygdala (AMYG) in both dominant and subordinate males. In contrast, dominant males had significantly higher Fos-ir densities in the medial preoptic area (MPOA) than subordinate males, whereas subordinate males expressed higher densities of Fos-ir in the anterior hypothalamus (AH) and central nucleus of the amygdala (CeA). Additionally, Fos-ir levels in the MPOA were significantly correlated with aggression and Fos-ir levels in the AH and CeA were correlated with defensive behavior. Together, our data indicate distinct patterns of neuronal activation associated with agonistic encounters in a behavior-specific manner in male greater long-tailed hamsters.

Lesion of the ventral tegmental area amplifies stimulation-induced Fos expression in the rat brain

Unilateral lesions of the ventral tegmental area (VTA), the key structure of the mesolimbic system, facilitate behavioral responses induced by electrical stimulation of the VTA in the contralateral hemisphere. In search of the neuronal mechanism behind this phenomenon, Fos expression was used to measure neuronal activation of the target mesolimbic structures in rats subjected to unilateral electrocoagulation and simultaneously to contralateral electrical stimulation of the VTA (L/S group). These were compared to the level of mesolimbic activation after unilateral electrocoagulation of the VTA (L group), unilateral electrical stimulation of the VTA (S group) and bilateral electrode implantation into the VTA in the sham (Sh) group. We found that unilateral stimulation of the VTA alone increased the density of Fos containing neurons in the ipsilateral mesolimbic target structures: nucleus accumbens, lateral septum and amygdala in comparison with the sham group. However, unilateral lesion of the VTA was devoid of effect in non-stimulated (L) rats and it significantly amplified the stimulation-induced Fos-immunoreactivity (L/S vs S group). Stimulation of the VTA performed after contralateral lesion (L/S) evoked strong bilateral induction of Fos expression in the mesolimbic structures involved in motivation and reward (nucleus accumbens and lateral septum) and the processing of the reinforcing properties of olfactory stimuli (anterior cortical amygdaloid nucleus) in parallel with facilitation of behavioral function measured as shortened latency of eating or exploration. Our data suggest that VTA lesion sensitizes mesolimbic system to stimuli by suppressing an inhibitory influence of brain areas afferenting the VTA.

Increased apoptosis during neonatal brain development underlies the adult behavioral deficits seen in mice lacking a functional paternally expressed gene 3 (Peg3)

Inactivation of the maternally imprinted, paternally expressed gene 3 (Peg3) induces deficits in olfactory function, sexual and maternal behaviors, oxytocin neuron number, metabolic homeostasis and growth. Peg3 is expressed in a number of developing hypothalamic and basal forebrain structures and is a component of the P53 apoptosis pathway. Peg3 inactivation in neuronal cell culture lines inhibits P53 mediated apoptosis, which is important in the early postnatal development and sexual differentiation of the brain. In this study, we investigated the effect of inactivating the Peg3 gene on the incidence of caspase 3 positive cells (a marker of apoptosis) in 4- and 6-day postpartum mouse brain. Inactivating the Peg3 gene resulted in an increase in the incidence of total forebrain caspase 3 positive cells at 4 and 6 days postpartum. Increases in specific neuroanatomical regions including the bed nucleus of the stria terminalis, nucleus accumbens, caudate putamen, medial pre-optic area, arcuate nucleus, medial amygdala, anterior cortical and posteriodorsal amygdaloid nuclei, were also observed. In wild-type mice, sex differences in the incidence of caspase 3 positive cells in the medial amygdala, bed nucleus of the stria terminalis, nucleus accumbens, arcuate nucleus and the M2 motor cortex, were also observed. This neural sex difference was ameliorated in the Peg-3 mutant. These findings suggest that the neuronal and behavioral deficits seen in mice lacking a functional Peg3 gene are mediated by increases in the incidence of early neonatal apoptosis in neuroanatomical regions important for reproductive behavior, olfactory and pheromonal processing, thermoregulation and reward.

Expression of P2X 5 receptors in the mouse CNS

P2X receptors are ATP-gated cationic channels composed of seven known subunits (P2X 1-7) which are involved in different functions in neural tissue. The present study investigates the P2X 5 receptor expression pattern in the mouse CNS using immunohistochemistry and in situ hybridization histochemistry. The specificity of the immunostaining has been verified by pre-absorption, Western blot and in situ hybridization methods. Heavy P2X 5 receptor immunostaining was observed in the mitral cells of the olfactory bulb; cerebral cortex; globus pallidum, anterior cortical amygdaloid nucleus, amygdalohippocampal area of subcortical telencephalon; anterior nuclei, anteroventral nucleus, ventrolateral nucleus of thalamus; supraoptic nucleus, ventromedial nucleus, arcuate nucleus of hypothalamus; substantia nigra of midbrain; pontine nuclei, mesencephalic trigeminal nucleus, motor trigeminal nucleus, ambiguous nucleus, inferior olive, hypoglossal nucleus, dorsal motor vagus nucleus, area postrema of hindbrain; Purkinje cells of cerebellum; and spinal cord. The identification of extensive P2X 5 receptor immunoreactivity and mRNA distribution within the CNS of the mouse demonstrated here is consistent with a role for extracellular ATP acting as a fast neurotransmitter.