Comparison of Dopamine Uptake in the Basolateral Amygdaloid Nucleus, Caudate-Putamen, and Nucleus Accumbens of the Rat

Abstract: Regional differences in the kinetics and pharmacological inhibition of dopamine uptake were investigated with fast-scan cyclic voltammetry in both the intact rat brain and a brain slice preparation. The regions compared were the basolateral amygdaloid nucleus, caudate-putamen, and nucleus accumbens. The frequency dependence of dopamine efflux evoked in vivo by electrical stimulation of the medial forebrain bundle was evaluated by nonlinear curve fitting with a Michaelis-Menten-based kinetic model. The K _m for dopamine uptake was found to be significantly higher in the basolateral amygdala (0.6 µ M ) than in the other two regions (0.2 µ M ), whereas the V _max value for dopamine uptake in the basolateral amygdala was significantly lower (0.49 µ M /s vs. 3.8 and 2.4 µ M /s in the caudate and accumbens, respectively). Similar kinetics were also obtained in brain slices. Addition of a dopamine uptake inhibitor, cocaine or nomifensine (10 µ M ), to the perfusion buffer increased the apparent K _m value >25-fold in slices of both the caudate-putamen and nucleus accumbens. In contrast, neither uptake inhibitor had an observable effect in the basolateral amygdaloid nucleus. Thus, dopamine uptake in the rat brain is regionally distinct with regard to rate, affinity, and sensitivity to competitive inhibition.     

Effects of Typical and Atypical Antipsychotic Drugs on Rat Brain Muscarinic Receptors

Quantitative in vitro autoradiography was used to examine changes in muscarinic M1/M4 and M2/M4 receptors (targeted with [³H]pirenzepine and [³H]AF-DX384 respectively), in rats treated with the typical (haloperidol) and atypical (clozapine and olanzapine) antipsychotic medications for a period of 36 days. Rats were sacrificed at either 2 h or 48 h after the last drug administration to examine immediate effects as well as the effects at 48 h after drug withdrawal. Haloperidol significantly increased [³H]pirenzepine binding in the dentate gyrus (37%) and in the CA1 region of the hippocampus (34%) in animals sacrificed 2 h after the last drug administration compared to controls. Similarly, clozapine significantly increased [³H]pirenzepine binding in dentate gyrus (29%) in rats sacrificed 2 h after the last drug administration compared to controls. Haloperidol decreased [³H]AF-DX384 binding in the basolateral nucleus of the amygdala (20%) in the rats sacrificed 48 h after the last drug administration compared to controls. These findings suggest that muscarinic receptors and limbic brain regions such as hippocampus and amygdala might represent common targets that mediate beneficial clinical effects of antipsychotic drugs.     

Characterization by high performance liquid chromatography of nuclear metabolites of testosterone in the brains of male rhesus monkeys

Testosterone (T) restores the potency of castrated male rhesus monkeys, and our autoradiographic data have demonstrated that ³H-T or its metabolites concentrate in cell nuclei in the corticomedial amygdala, bed nucleus of stria terminalis, preoptic area, and hypothalamus. In rat, ³H-estradiol (³H-E₂) is a major nuclear metabolite of ³H-T in areas of the limbic system, but comparable data are lacking for the primate. We have therefore developed an improved technique using high performance liquid chromatography for investigating metabolites of ³H-T that accumulate in cell nuclei in small amounts of tissue obtained from the brain of the rhesus monkey. Two castrated male rhesus monkeys were injected with 5 mCi of ³H-T and were killed 30 min later. In amygdala, preoptic area-bed nucleus of stria terminalis, and hypothalamus, 48–70% of the nuclear radioactivity was in the form of ³H-E₂ (Type I tissues). In six other brain areas and in pituitary, 35–85% of the nuclear radioactivity was in the form of ³H-T (Type II tissues), whereas in genital tract tissues, 86–99% of the nuclear radioactivity was in the form of ³H-dihydrotestosterone (³H-DHT) (Type III tissues). In plasma and in supernatants from both Type I and Type II tissues, the proportions of ³H-T were high, and ³H-E₂ did not exceed 10% of the total extractable radioactivity. These data suggest that, as in rodents, some of the central actions of T in primates may be mediated by estrogen target neurons.     

Abnormal Astrocytosis in the Basal Ganglia Pathway of Git1?/? Mice

Attention deficit/hyperactivity disorder (ADHD) is one of the most common neurodevelopmental disorders, affecting approximately 5% of children. However, the neural mechanisms underlying its development and treatment are yet to be elucidated. In this study, we report that an ADHD mouse model, which harbors a deletion in the Git1 locus, exhibits severe astrocytosis in the globus pallidus (GP) and thalamic reticular nucleus (TRN), which send modulatory GABAergic inputs to the thalamus. A moderate level of astrocytosis was displayed in other regions of the basal ganglia pathway, including the ventrobasal thalamus and cortex, but not in other brain regions, such as the caudate putamen, basolateral amygdala, and hippocampal CA1. This basal ganglia circuit-selective astrocytosis was detected in both in adult (2–3 months old) and juvenile (4 weeks old) Git1^−/− mice, suggesting a developmental origin. Astrocytes play an active role in the developing synaptic circuit; therefore, we performed an immunohistochemical analysis of synaptic markers. We detected increased and decreased levels of GABA and parvalbumin (PV), respectively, in the GP. This suggests that astrocytosis may alter synaptic transmission in the basal ganglia. Intriguingly, increased GABA expression colocalized with the astrocyte marker, GFAP, indicative of an astrocytic origin. Collectively, these results suggest that defects in basal ganglia circuitry, leading to impaired inhibitory modulation of the thalamus, are neural correlates for the ADHD-associated behavioral manifestations in Git1^−/− mice.     

GABA concentration and GABAergic neuron populations in limbic areas are differentially altered by brain serotonin deficiency in Tph2 knockout mice

While tryptophan hydroxylase-2 (Tph2) null mutant (Tph2 ^?/?) mice are completely deficient in brain serotonin (5-HT) synthesis, the formation of serotonergic neurons and pathfinding of their projections are not impaired. However, 5-HT deficiency, during development and in the adult, might affect morphological and functional parameters of other neural systems. To assess the influence of 5-HT deficiency on γ-amino butyric acid (GABA) systems, we carried out measurements of GABA concentrations in limbic brain regions of adult male wildtype (wt), heterozygous (Tph2 ^+/?) and Tph2 ^?/? mice. In addition, unbiased stereological estimation of GABAergic interneuron numbers and density was performed in subregions of amygdala and hippocampus. Amygdala and prefrontal cortex displayed significantly increased and decreased GABA concentrations, respectively, exclusively in Tph2 ^+/? mice while no changes were detected between Tph2 ^?/? and wt mice. In contrast, in the hippocampus, increased GABA concentrations were found in Tph2 ^?/? mice. While total cell density in the anterior basolateral amygdala did not differ between genotypes, the number and density of the GABAergic interneurons were significantly decreased in Tph2 ^?/? mice, with the group of parvalbumin (PV)-immunoreactive (ir) interneurons contributing somewhat less to the decrease than that of non-PV-ir GABAergic interneurons. Major morphological changes were also absent in the dorsal hippocampus, and only a trend toward reduced density of PV-ir cells was observed in the CA3 region of Tph2 ^?/? mice. Our findings are the first to document that life-long reduction or complete lack of brain 5-HT transmission causes differential changes of GABA systems in limbic regions which are key players in emotional learning and memory processes. The changes likely reflect a combination of developmental alterations and functional adaptations of emotion circuits to balance the lack of 5-HT, and may underlie altered emotional behavior in 5-HT-deficient mice. Taken together, our findings provide further insight into the mechanisms how life-long 5-HT deficiency impacts the pathogenesis of anxiety- and fear-related disorders.     

Basolateral localization of anion exchanger 2 (AE2) and actin in acid-secreting (parietal) cells of the human stomach

Basolateral uptake of chloride by the HCl-secreting parietal cells of the gastric (oxyntic) glands is most likely mediated by a HCO^– ₃/Cl^– anion exchange mechanism. Circumstantial evidence indicates that in rodents the anion exchange proceeds through an anion exchanger 2(AE2)-like membrane protein. In the present study, we raised antibodies against a bacterial fusion protein expressing a -26-kDa portion of the human AE2 sequence. These antibodies were used to identify and localize AE2 in the human stomach. Here we report that the mucosa of the human stomach expresses an 160-kDa immunoreactive form of AE2 containing the AE2-specific exoplasmic domain (Z-loop) as identified by polymerase chain reaction. Immunostaining specific for AE2 was restricted to the basolateral membrane domain of parietal cells and was also detected in small epithelial cells localized in the glandular isthmus region. The latter cells most likely represent pre-parietal cells. Parietal cells were identified by simultaneous and sequential labelling with antibodies against the gastric H⁺, K⁺-ATPase and actin, respectively. Both actin and the H⁺, K⁺-ATPase were localized along the apical membrane of parietal cells and the membrane of their secretory intracellular canaliculi. In addition, actin was shown to be colocalized with AE2 along the basolateral cell surface. Discontinuous staining for AE2 coincided with infoldings of the basolateral plasma membrane labelled by the actin antibody. These observations indicate that AE2 might be placed at specialized (folded) microdomains of the basolateral cell surface by linkage to the actin-based cytoskeleton.Large parts of this publication belong to the MD thesis of B. Warrings. B. Warrings and T. Jöns should be considered alphabetically listed first authors who made equally strong contributions to this study     

Association of Body Mass and Brain Activation during Gastric Distention: Implications for Obesity

Background

Gastric distention (GD), as it occurs during meal ingestion, signals a full stomach and it is one of the key mechanisms controlling food intake. Previous studies on GD showed lower activation of the amygdala for subjects with higher body mass index (BMI). Since obese subjects have dopaminergic deficits that correlate negatively with BMI and the amygdala is innervated by dopamine neurons, we hypothesized that BMI would correlate negatively with activation not just in the amygdala but also in other dopaminergic brain regions (midbrain and hypothalamus).

Methodology/Principal Findings

We used functional magnetic resonance imaging (fMRI) to evaluate brain activation during GD in 24 healthy subjects with BMI range of 20–39 kg/m². Using multiple regression and cross-correlation analyses based on a family-wise error corrected threshold P = 0.05, we show that during slow GD to maximum volumes of 500 ml and 700 ml subjects with increased BMI had increased activation in cerebellum and left posterior insula, and decreased activation of dopaminergic (amygdala, midbrain, hypothalamus, thalamus) and serotonergic (pons) brain regions and anterior insula, regions that were functionally interconnected with one another.

Conclusions

The negative correlation between BMI and BOLD responses to gastric distention in dopaminergic (midbrain, hypothalamus, amygdala, thalamus) and serotonergic (pons) brain regions is consistent with disruption of dopaminergic and serotonergic signaling in obesity. In contrast the positive correlation between BMI and BOLD responses in posterior insula and cerebellum suggests an opposing mechanism that promotes food intake in obese subjects that may underlie their ability to consume at once large food volumes despite increasing gastric distention.     

Structural Connectivity of the Developing Human Amygdala

A large corpus of research suggests that there are changes in the manner and degree to which the amygdala supports cognitive and emotional function across development. One possible basis for these developmental differences could be the maturation of amygdalar connections with the rest of the brain. Recent functional connectivity studies support this conclusion, but the structural connectivity of the developing amygdala and its different nuclei remains largely unstudied. We examined age related changes in the DWI connectivity fingerprints of the amygdala to the rest of the brain in 166 individuals of ages 5-30. We also developed a model to predict age based on individual-subject amygdala connectivity, and identified the connections that were most predictive of age. Finally, we segmented the amygdala into its four main nucleus groups, and examined the developmental changes in connectivity for each nucleus. We observed that with age, amygdalar connectivity becomes increasingly sparse and localized. Age related changes were largely localized to the subregions of the amygdala that are implicated in social inference and contextual memory (the basal and lateral nuclei). The central nucleus’ connectivity also showed differences with age but these differences affected fewer target regions than the basal and lateral nuclei. The medial nucleus did not exhibit any age related changes. These findings demonstrate increasing specificity in the connectivity patterns of amygdalar nuclei across age.     

Basolateral Amygdala Lesion Inhibits the Development of Pain Chronicity in Neuropathic Pain Rats

Background

Chronicity of pain is one of the most interesting questions in chronic pain study. Clinical and experimental data suggest that supraspinal areas responsible for negative emotions such as depression and anxiety contribute to the chronicity of pain. The amygdala is suspected to be a potential structure for the pain chronicity due to its critical role in processing negative emotions and pain information.

Objective

This study aimed to investigate whether amygdala or its subregions, the basolateral amygdala (BLA) and the central medial amygdala (CeA), contributes to the pain chronicity in the spared nerve injury (SNI)-induced neuropathic pain model of rats.

Methodology/Principal Findings

(1) Before the establishment of the SNI-induced neuropathic pain model of rats, lesion of the amygdaloid complex with stereotaxic injection of ibotenic acid (IBO) alleviated mechanical allodynia significantly at days 7 and 14, even no mechanical allodynia at day 28 after SNI; Lesion of the BLA, but not the CeA had similar effects; (2) however, 7 days after SNI when the neuropathic pain model was established, lesion of the amygdala complex or the BLA or the CeA, mechanical allodynia was not affected.

Conclusion

These results suggest that BLA activities in the early stage after nerve injury might be crucial to the development of pain chronicity, and amygdala-related negative emotions and pain-related memories could promote pain chronicity.     

Recording and Analysis of Circadian Rhythms in Running-wheel Activity in Rodents

When rodents have free access to a running wheel in their home cage, voluntary use of this wheel will depend on the time of day^1-5. Nocturnal rodents, including rats, hamsters, and mice, are active during the night and relatively inactive during the day. Many other behavioral and physiological measures also exhibit daily rhythms, but in rodents, running-wheel activity serves as a particularly reliable and convenient measure of the output of the master circadian clock, the suprachiasmatic nucleus (SCN) of the hypothalamus. In general, through a process called entrainment, the daily pattern of running-wheel activity will naturally align with the environmental light-dark cycle (LD cycle; e.g. 12 hr-light:12 hr-dark). However circadian rhythms are endogenously generated patterns in behavior that exhibit a ~24 hr period, and persist in constant darkness. Thus, in the absence of an LD cycle, the recording and analysis of running-wheel activity can be used to determine the subjective time-of-day. Because these rhythms are directed by the circadian clock the subjective time-of-day is referred to as the circadian time (CT). In contrast, when an LD cycle is present, the time-of-day that is determined by the environmental LD cycle is called the zeitgeber time (ZT).Although circadian rhythms in running-wheel activity are typically linked to the SCN clock^6-8, circadian oscillators in many other regions of the brain and body^9-14 could also be involved in the regulation of daily activity rhythms. For instance, daily rhythms in food-anticipatory activity do not require the SCN^15,16 and instead, are correlated with changes in the activity of extra-SCN oscillators^17-20. Thus, running-wheel activity recordings can provide important behavioral information not only about the output of the master SCN clock, but also on the activity of extra-SCN oscillators. Below we describe the equipment and methods used to record, analyze and display circadian locomotor activity rhythms in laboratory rodents.     

Altered Resting-State Amygdala Functional Connectivity after 36 Hours of Total Sleep Deprivation

Objectives

Recent neuroimaging studies have identified a potentially critical role of the amygdala in disrupted emotion neurocircuitry in individuals after total sleep deprivation (TSD). However, connectivity between the amygdala and cerebral cortex due to TSD remains to be elucidated. In this study, we used resting-state functional MRI (fMRI) to investigate the functional connectivity changes of the basolateral amygdala (BLA) and centromedial amygdala (CMA) in the brain after 36 h of TSD.

Materials and Methods

Fourteen healthy adult men aged 25.9±2.3 years (range, 18–28 years) were enrolled in a within-subject crossover study. Using the BLA and CMA as separate seed regions, we examined resting-state functional connectivity with fMRI during rested wakefulness (RW) and after 36 h of TSD.

Results

TSD resulted in a significant decrease in the functional connectivity between the BLA and several executive control regions (left dorsolateral prefrontal cortex [DLPFC], right dorsal anterior cingulate cortex [ACC], right inferior frontal gyrus [IFG]). Increased functional connectivity was found between the BLA and areas including the left posterior cingulate cortex/precuneus (PCC/PrCu) and right parahippocampal gyrus. With regard to CMA, increased functional connectivity was observed with the rostral anterior cingulate cortex (rACC) and right precentral gyrus.

Conclusion

These findings demonstrate that disturbance in amygdala related circuits may contribute to TSD psychophysiology and suggest that functional connectivity studies of the amygdala during the resting state may be used to discern aberrant patterns of coupling within these circuits after TSD.     

Zolpidem Displays Heterogeneity in Its Binding to the Nonhuman Primate Benzodiazepine Receptor In Vivo

Abstract: The distinctive pharmacological activity of zolpidem in rats compared with classical benzodiazepines has been related to its differential affinity for benzodiazepine receptor (BZR) subtypes. By contrast, in nonhuman primates the pharmacological activity of zolpidem was found to be quite similar to that of classical BZR agonists. In an attempt to explain this discrepancy, we examined the ability of zolpidem to differentiate BZR subtypes in vivo in primate brain using positron emission tomography. The BZRs were specifically labeled with [¹¹C]flumazenil. Radiotracer displacement by zolpidem was monophasic in cerebellum and neocortex, with in vivo Hill coefficients close to 1. Conversely, displacement of [¹¹C]flumazenil was biphasic in hippocampus, amygdala, septum, insula, striatum, and pons, with Hill coefficients significantly smaller than 1, suggesting two different binding sites for zolpidem. In these cerebral regions, the half-maximal inhibitory doses for the high-affinity binding site were similar to those found in cerebellum and neocortex and ～100-fold higher for the low-affinity binding site. The low-affinity binding site accounted for <32% of the specific [¹¹C]-flumazenil binding. Such zolpidem binding characteristics contrast with those reported for rodents, where three different binding sites were found. Species differences in binding characteristics may explain why zolpidem has a distinctive pharmacological activity in rodents, whereas its pharmacological activity in primates is quite similar to that of classical BZR agonists, except for the absence of severe effects on memory functions, which may be due to the lack of substantial zolpidem affinity for a distinct BZR subtype in cerebral structures belonging to the limbic system.     

Social status and sex independently influence androgen receptor expression in the eusocial naked mole-rat brain

Naked mole-rats (Heterocephalus glaber) are eusocial rodents that live in large subterranean colonies including a single breeding female and 1-3 breeding males; all other members of the colony, known as subordinates, are reproductively suppressed. We recently found that naked mole-rats lack many of the sex differences in the brain and spinal cord commonly found in other rodents. Instead, neural morphology is influenced by breeding status, such that breeders, regardless of sex, have more neurons than subordinates in the ventromedial nucleus of the hypothalamus (VMH), and larger overall volumes of the bed nucleus of the stria terminalis (BST), paraventricular nucleus (PVN) and medial amygdala (MeA). To begin to understand how breeding status influences brain morphology, we examined the distribution of androgen receptor (AR) immunoreactivity in gonadally intact breeders and subordinates of both sexes. All animals had AR+ nuclei in many of the same regions positive for AR in other mammals, including the VMH, BST, PVN, MeA, and the ventral portion of the premammillary nucleus (PMv). We also observed diffuse labeling throughout the preoptic area, demonstrating that distribution of the AR protein in presumptive reproductive brain nuclei is well-conserved, even in a species that exhibits remarkably little sexual dimorphism. In contrast to other rodents, however, naked mole-rats lacked AR+ nuclei in the suprachiasmatic nucleus and hippocampus. Males had more AR+ nuclei in the MeA, VMH, and PMv than did females. Surprisingly, breeders had significantly fewer AR+ nuclei than subordinates in all brain regions examined (VMH, BST, PVN, MeA, and PMv). Thus, social status is strongly correlated with AR immunoreactivity in this eusocial species.     

A Method to Make a Craniotomy on the Ventral Skull of Neonate Rodents

The use of a craniotomy for in vivo experiments provides an opportunity to investigate the dynamics of diverse cellular processes in the mammalian brain in adulthood and during development. Although most in vivo approaches use a craniotomy to study brain regions located on the dorsal side, brainstem regions such as the pons, located on the ventral side remain relatively understudied. The main goal of this protocol is to facilitate access to ventral brainstem structures so that they can be studied in vivo using electrophysiological and imaging methods. This approach allows study of structural changes in long-range axons, patterns of electrical activity in single and ensembles of cells, and changes in blood brain barrier permeability in neonate animals. Although this protocol has been used mostly to study the auditory brainstem in neonate rats, it can easily be adapted for studies in other rodent species such as neonate mice, adult rodents and other brainstem regions.     

Amygdala-frontal interactions and reward expectancy

Recent evidence indicates that networks including the amygdala and prefrontal cortex provide a key interface between affect and cognition. Converging evidence from rodents, humans, and non-human primates indicates that interconnections between the basolateral complex of the amygdala and the orbitofrontal cortex are crucial to the formation and use of expectancies of reinforcers in the guidance of goal-directed behavior.     

Localization of DJ-1 protein in the murine brain

Mutations in the DJ-1 gene have been identified to cause Parkinson's disease. In humans, nonmutated DJ-1 is expressed in specific brain areas but seems to be expressed by astrocytes rather than by neurons. In contrast, DJ-1 mRNA is mainly found in neurons in the mouse brain. We have investigated the distribution of DJ-1 protein in the mouse brain and found that DJ-1 protein is predominantly expressed by neurons but can also be detected in astrocytes. Consistent with a global role of DJ-1 in the brain, we found immunoreactivity, for example, in cortical areas, hippocampus, basolateral amygdala, the reticular nucleus of the thalamus, zona incerta, and locus coeruleus. Within the substantia nigra, however, DJ-1 is localized in both neuronal and nonneuronal cells, suggesting a distinct role in this area.     

Face pictures reduce behavioural, autonomic, endocrine and neural indices of stress and fear in sheep

Faces are highly emotive stimuli and we find smiling or familiar faces both attractive and comforting, even as young babies. Do other species with sophisticated face recognition skills, such as sheep, also respond to the emotional significance of familiar faces? We report that when sheep experience social isolation, the sight of familiar sheep face pictures compared with those of goats or inverted triangles significantly reduces behavioural (activity and protest vocalizations), autonomic (heart rate) and endocrine (cortisol and adrenaline) indices of stress. They also increase mRNA expression of activity-dependent genes (c-fos and zif/268) in brain regions specialized for processing faces (temporal and medial frontal cortices and basolateral amygdala) and for emotional control (orbitofrontal and cingulate cortex), and reduce their expression in regions associated with stress responses (hypothalamic paraventricular nucleus) and fear (central and lateral amygdala). Effects on face recognition, emotional control and fear centres are restricted to the right brain hemisphere. Results provide evidence that face pictures may be useful for relieving stress caused by unavoidable social isolation in sheep, and possibly other animal species, including humans. The finding that sheep, like humans, appear to have a right brain hemisphere involvement in the control of negative emotional experiences also suggests that functional lateralization of brain emotion systems may be a general feature in mammals.     

Brain regions responsible for the expression of conditioned taste aversion in rats

Conditioned taste aversion (CTA) is acquired when the ingestion of a food is followed by malaise. CTA is a kind of fear learning making animals avoid subsequent intake of the food and show aversive behavior to the taste of the food. To elucidate the brain regions responsible for the expression of CTA, our previous electrophysiological and recent c-fos immunohistochemical studies have been reviewed. Among a variety of brain regions including the parabrachial nucleus, amygdala, insular cortex, supramammillary nucleus, nucleus accumbens, and ventral pallidum that are involved in different phases of CTA expression, the enhanced taste sensitivity to facilitate detection of the conditioned stimulus may originate in the central nucleus of the amygdala and the hedonic shift, from positive to negative, may originate in the basolateral nucleus of the amygdala.     

An Ex vivo Model of an Oligodendrocyte-directed T-Cell Attack in Acute Brain Slices

Death of oligodendrocytes accompanied by destruction of neurons and axons are typical histopathological findings in cortical and subcortical grey matter lesions in inflammatory demyelinating disorders like multiple sclerosis (MS). In these disorders, mainly CD8⁺ T-cells of putative specificity for myelin- and oligodendrocyte-related antigens are found, so that neuronal apoptosis in grey matter lesions may be a collateral effect of these cells. Different types of animal models are established to study the underlying mechanisms of the mentioned pathophysiological processes. However, although they mimic some aspects of MS, it is impossible to dissect the exact mechanism and time course of ‘‘collateral’’ neuronal cell death. To address this course, here we show a protocol to study the mechanisms and time response of neuronal damage following an oligodendrocyte-directed CD8⁺ T cell attack. To target only the myelin sheath and the oligodendrocytes, in vitro activated oligodendrocyte-specific CD8⁺ T-cells are transferred into acutely isolated brain slices. After a defined incubation period, myelin and neuronal damage can be analysed in different regions of interest. Potential applications and limitations of this model will be discussed.     

Autoradiographic Analysis of [3H]Kainic Acid Binding in Primate Braind

Abstract

The distribution of [³H]kainic acid binding sites was studied in the primate brain using semiquantitative autoradiography. The highest levels of binding were observed in the hippocampal area CA3 and the dentate gyrus. The deep layers of pyriform, cingulate and insular cortex, the central nucleus of the amygdala and the caudate nucleus also displayed high levels of [³H]kainic acid binding. Although these areas receive putative excitatory amino acid-containing afferents, other regions containing a similar input displayed low levels of binding. Some similarities were apparent between the distribution of binding sites and pathological changes in human neurodegenerative disorders such as temporal lobe epilepsy.